Bulat, Zorica

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Authority KeyName Variants
orcid::0000-0001-9830-8772
  • Bulat, Zorica (133)
  • Plamenac-Bulat, Zorica (7)
Projects
Improvement and development of hygienic and technological procedures in production of animal originating foodstuffs with the aim of producing high-quality and safe products competetive on the global market Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200161 (University of Belgrade, Faculty of Pharmacy)
DecodExpo - Decoding the Role of Exposome in Endocrine Health Biomarkers of organ damage and dysfunction
Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) Agence Nationale de la Recherche ANR-13-CESA-008-Cadmidia
“Improving anti-cancer immunotherapy efficacy of CAR-T cells or PD-1/PD-L1 inhibitors by combining immune modulators”, funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, in the framework of scientific cooperation with the People’s Republic of China (451-03-1203/2021-09) Bezbednost hrane, hemijski kontaminanti i integrativna procena rizika
Medical Research Council of UK (award reference number MR/R005699/1 ) Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije kroz međunarodni projekat između Republike Srbije i NR Kine: „Povećanje efikasnosti terapije karcinoma kombinacijom CAR-T ćelija ili PD-1/PD-L1 inhibitora pomoću imunomodulatora” (451-03-1203/2021-09).
Ministry of Science and Environmental Protection, Republic of Serbia - 1432 Ministry of Science and Ministry of Health of Montenegro through the Project No. 03-401
Oklahoma State University Center for Health Sciences (OVPR) Pilot/Seed Grant (AG154391) and Presidential Fellowship (to KM, LY, and LV) D.R.W.; Oklahoma State UniversityCenter for Health Sciences Pilot/Seed Grant (1-54357; D.W.)
OSUCHS 154357 (to D.R.W.) State’s Key Project of Research and Development Plan of the People’s Republic of China (No. 2021YFE0110600)
The animal study protocol was approved by the Ethics Committee of Military Medical Academy in Belgrade, Serbia (no. 9667–1/2011) The Ministry of Education, Science and Technological Development of the Republic of Serbia, in the framework of scientific cooperation with the People’s Republic of China (451-03-1203/2021-09)
The Ministry of Education, Science and Technological Development of the Republic of Serbia, in the framework of scientific cooperation with the People’s Republic of China (451-03-1203/2021–09) The Ministry of Science, Education, and Sports of the Republic of Croatia (project No. 022-0222411-2408)
The project “Improving anti-cancer immunotherapy efficacy of CAR-T cells or PD-1/PD-L1 inhibitors by combining immune modulators” The Science Fund of the Republic of Serbia, PROMIS, Grant No 6066532
The State’s Key Project of Research and Development Plan of the People’s Republic of China (No. 2021YFE0110600) The study was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development ofWorld-Class Research Centers “Digital biodesign and personalized healthcare” 075-15-2020-926.
University of Westminster, School of Life Sciences Research Enhancement Grant 2020 P.U.-O., M.M. is supported by University of Westminster SLS PhD Studentship

Author's Bibliography

In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function

Vukelić, Dragana; Buha-Đorđević, Aleksandra; Anđelković, Milena; Baralić, Katarina; Ćurčić, Marijana; Đukić-Ćosić, Danijela; Antonijević, Biljana; Bulat, Zorica

(Elsevier, 2023)

TY  - JOUR
AU  - Vukelić, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Anđelković, Milena
AU  - Baralić, Katarina
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5033
AB  - The purpose of this study was to examine the impact of low doses of lead (Pb) on levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid-related antibodies (anti-Tg and anti-TPO) in the rat model, as well as genes that are related to Pb and thyroid function, relationships between genes, biological processes, molecular processes, and pathways using an in silico approach. Male rats were randomized into seven groups (n = 42), one control group and six groups that received a range of Pb doses: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight (b.w.). Dose-response modelling was performed by PROAST software using model averaging method. The Comparative Toxicogenomics Database, GeneMANIA server, and ToppGene Suite portal were used as the main bioinformatic tools in this analysis. The results of our study have shown that low Pb doses induced elevation of thyroid hormones (T4, FT4, and TSH) in rats after subacute exposure, while had no impact on T3, FT3, anti-TPO, and anti-Tg, indicating hyperthyroidism. Dose-dependent effects were increases in T4 and FT4, with the lowest benchmark dose derived for FT4 levels. In silico toxicogenomic data analysis showed that the main molecular pathways/process related to Pb-induced hyperthyroidism are connected with 14 genes involved in antioxidant defense and Se-dependent processes. The results presented here may be useful in further investigation of the health impacts of low-level Pb exposure on thyroid function and endocrine disruption effects.
PB  - Elsevier
T2  - Environmental Research
T1  - In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function
VL  - 237
DO  - 10.1016/j.envres.2023.117035
ER  - 
@article{
author = "Vukelić, Dragana and Buha-Đorđević, Aleksandra and Anđelković, Milena and Baralić, Katarina and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Antonijević, Biljana and Bulat, Zorica",
year = "2023",
abstract = "The purpose of this study was to examine the impact of low doses of lead (Pb) on levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid-related antibodies (anti-Tg and anti-TPO) in the rat model, as well as genes that are related to Pb and thyroid function, relationships between genes, biological processes, molecular processes, and pathways using an in silico approach. Male rats were randomized into seven groups (n = 42), one control group and six groups that received a range of Pb doses: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight (b.w.). Dose-response modelling was performed by PROAST software using model averaging method. The Comparative Toxicogenomics Database, GeneMANIA server, and ToppGene Suite portal were used as the main bioinformatic tools in this analysis. The results of our study have shown that low Pb doses induced elevation of thyroid hormones (T4, FT4, and TSH) in rats after subacute exposure, while had no impact on T3, FT3, anti-TPO, and anti-Tg, indicating hyperthyroidism. Dose-dependent effects were increases in T4 and FT4, with the lowest benchmark dose derived for FT4 levels. In silico toxicogenomic data analysis showed that the main molecular pathways/process related to Pb-induced hyperthyroidism are connected with 14 genes involved in antioxidant defense and Se-dependent processes. The results presented here may be useful in further investigation of the health impacts of low-level Pb exposure on thyroid function and endocrine disruption effects.",
publisher = "Elsevier",
journal = "Environmental Research",
title = "In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function",
volume = "237",
doi = "10.1016/j.envres.2023.117035"
}
Vukelić, D., Buha-Đorđević, A., Anđelković, M., Baralić, K., Ćurčić, M., Đukić-Ćosić, D., Antonijević, B.,& Bulat, Z.. (2023). In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function. in Environmental Research
Elsevier., 237.
https://doi.org/10.1016/j.envres.2023.117035
Vukelić D, Buha-Đorđević A, Anđelković M, Baralić K, Ćurčić M, Đukić-Ćosić D, Antonijević B, Bulat Z. In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function. in Environmental Research. 2023;237.
doi:10.1016/j.envres.2023.117035 .
Vukelić, Dragana, Buha-Đorđević, Aleksandra, Anđelković, Milena, Baralić, Katarina, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Antonijević, Biljana, Bulat, Zorica, "In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function" in Environmental Research, 237 (2023),
https://doi.org/10.1016/j.envres.2023.117035 . .

Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different

Baralić, Katarina; Marić, Đurđica; Vukelić, Dragana; Antonijević-Miljaković, Evica; Anđelković, Milena; Antonijević, Biljana; Đukić-Ćosić, Danijela; Bulat, Zorica; Buha-Đorđević, Aleksandra

(Elsevier B.V., 2023)

TY  - JOUR
AU  - Baralić, Katarina
AU  - Marić, Đurđica
AU  - Vukelić, Dragana
AU  - Antonijević-Miljaković, Evica
AU  - Anđelković, Milena
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4915
AB  - The current study aimed to examine the effect of toxic metal(oid) mixtures (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and nickel (Ni)) on female reproductive function in Wistar rats after the 28- and 90-day exposure to dose levels calculated on the basis of the previously conducted human study. Experimental groups included: 2 controls (28- and 90-day), treated groups - doses based on: median– F2 (28) and F2(90) and 95th percentile concentrations in the general human population – F3(28) and F3(90); calculated lower Benchmark dose confidence limit (BMDL) for effects on hormone levels – F1(28) and F1(90) and a group given the doses calculated on the basis of the reference values from the literature (F4(28)). Blood and ovarian samples were collected for sex hormones and ovary redox status analysis. After 28-day exposure, changes were present both in prooxidants and antioxidants. However, after the 90-day exposure redox status imbalance was majorly caused by the disturbance of antioxidants. Changes in some parameters were observed even after exposure to the lowest doses. After 28-day exposure, the strongest dose-response relationship was found between hormones: LH and FSH and toxic metal(oid)s and, after 90-day exposure, between investigated redox status parameters: sulfhydryl groups, ischemia-modified albumin and nuclear factor erythroid 2–related factor 2 (Nrf2) and toxic metal(oid)s. Low obtained BMDLs and narrow Benchmark intervals for toxic metal(oid)s and some of the parameters might confirm the “no-threshold” paradigm. This study indicates possible detrimental effects of prolonged exposure to real-life mixtures of toxic metal(oid) on female reproductive function.
PB  - Elsevier B.V.
T2  - Science of the Total Environment
T1  - Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different
VL  - 895
DO  - 10.1016/j.scitotenv.2023.165181
ER  - 
@article{
author = "Baralić, Katarina and Marić, Đurđica and Vukelić, Dragana and Antonijević-Miljaković, Evica and Anđelković, Milena and Antonijević, Biljana and Đukić-Ćosić, Danijela and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "The current study aimed to examine the effect of toxic metal(oid) mixtures (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and nickel (Ni)) on female reproductive function in Wistar rats after the 28- and 90-day exposure to dose levels calculated on the basis of the previously conducted human study. Experimental groups included: 2 controls (28- and 90-day), treated groups - doses based on: median– F2 (28) and F2(90) and 95th percentile concentrations in the general human population – F3(28) and F3(90); calculated lower Benchmark dose confidence limit (BMDL) for effects on hormone levels – F1(28) and F1(90) and a group given the doses calculated on the basis of the reference values from the literature (F4(28)). Blood and ovarian samples were collected for sex hormones and ovary redox status analysis. After 28-day exposure, changes were present both in prooxidants and antioxidants. However, after the 90-day exposure redox status imbalance was majorly caused by the disturbance of antioxidants. Changes in some parameters were observed even after exposure to the lowest doses. After 28-day exposure, the strongest dose-response relationship was found between hormones: LH and FSH and toxic metal(oid)s and, after 90-day exposure, between investigated redox status parameters: sulfhydryl groups, ischemia-modified albumin and nuclear factor erythroid 2–related factor 2 (Nrf2) and toxic metal(oid)s. Low obtained BMDLs and narrow Benchmark intervals for toxic metal(oid)s and some of the parameters might confirm the “no-threshold” paradigm. This study indicates possible detrimental effects of prolonged exposure to real-life mixtures of toxic metal(oid) on female reproductive function.",
publisher = "Elsevier B.V.",
journal = "Science of the Total Environment",
title = "Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different",
volume = "895",
doi = "10.1016/j.scitotenv.2023.165181"
}
Baralić, K., Marić, Đ., Vukelić, D., Antonijević-Miljaković, E., Anđelković, M., Antonijević, B., Đukić-Ćosić, D., Bulat, Z.,& Buha-Đorđević, A.. (2023). Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different. in Science of the Total Environment
Elsevier B.V.., 895.
https://doi.org/10.1016/j.scitotenv.2023.165181
Baralić K, Marić Đ, Vukelić D, Antonijević-Miljaković E, Anđelković M, Antonijević B, Đukić-Ćosić D, Bulat Z, Buha-Đorđević A. Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different. in Science of the Total Environment. 2023;895.
doi:10.1016/j.scitotenv.2023.165181 .
Baralić, Katarina, Marić, Đurđica, Vukelić, Dragana, Antonijević-Miljaković, Evica, Anđelković, Milena, Antonijević, Biljana, Đukić-Ćosić, Danijela, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different" in Science of the Total Environment, 895 (2023),
https://doi.org/10.1016/j.scitotenv.2023.165181 . .

Cadmium and lead implication in testis cancer; is there a connection?

Anđelković, Milena; Buha-Đorđević, Aleksandra; Vukelić, Dragana; Đukić-Ćosić, Danijela; Aćimović, Miodrag; Bojanić, Nebojša; Bartolović, Daniela; Bulat, Petar; Antonijević, Biljana; Bulat, Zorica

(Elsevier Ltd, 2023)

TY  - JOUR
AU  - Anđelković, Milena
AU  - Buha-Đorđević, Aleksandra
AU  - Vukelić, Dragana
AU  - Đukić-Ćosić, Danijela
AU  - Aćimović, Miodrag
AU  - Bojanić, Nebojša
AU  - Bartolović, Daniela
AU  - Bulat, Petar
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4675
AB  - Testis cancer (TC) is the most common malignancy of young men. Current evidence from studies, alongside genetics and hormonal status, suggests a significant role of toxic metals, cadmium (Cd) and lead (Pb), in the origin and development of TC. Besides oxidative stress and endocrine disruption, interaction with bioelements is one of the critical mechanisms of Cd and Pb toxicity and malign transformation. This study aimed to investigate metal levels in blood, healthy, and tumor testis tissue and to reveal hormone, oxidative status, and bioelements levels in patients with TC. The study enrolled 52 patients with TC and 61 healthy volunteers. Toxic metals and bioelements levels were analyzed by atomic absorption spectrophotometry (AAS) while electrochemiluminescence immunoassay (ECLIA) and spectrophotometry methods were used for hormone and oxidative parameters evaluation. Significantly higher blood Cd levels were depicted in TC cohort. Furthermore, blood Cd elevation was associated with a 1.98 higher probability of TC developing. However, a metal concentration between healthy and tumor testis tissue did not differ significantly. Lower levels of estradiol and testosterone, established in a cohort of TC patients, followed the significant role of hormones in TC development. At the same time, ischemia-modified albumin (IMA) has been recognized as a parameter with very good accuracy as a potential diagnostic marker for TC. The study revealed different distribution patterns of copper (Cu) and zinc (Zn) in the three compartments of the patients, as well significant correlation between essential metals Cu/Zn and toxic metals Cd/Pb indicating metal-metal interactions as pivotal mechanisms of metals toxicity.
PB  - Elsevier Ltd
T2  - Chemosphere
T1  - Cadmium and lead implication in testis cancer; is there a connection?
VL  - 330
DO  - 10.1016/j.chemosphere.2023.138698
ER  - 
@article{
author = "Anđelković, Milena and Buha-Đorđević, Aleksandra and Vukelić, Dragana and Đukić-Ćosić, Danijela and Aćimović, Miodrag and Bojanić, Nebojša and Bartolović, Daniela and Bulat, Petar and Antonijević, Biljana and Bulat, Zorica",
year = "2023",
abstract = "Testis cancer (TC) is the most common malignancy of young men. Current evidence from studies, alongside genetics and hormonal status, suggests a significant role of toxic metals, cadmium (Cd) and lead (Pb), in the origin and development of TC. Besides oxidative stress and endocrine disruption, interaction with bioelements is one of the critical mechanisms of Cd and Pb toxicity and malign transformation. This study aimed to investigate metal levels in blood, healthy, and tumor testis tissue and to reveal hormone, oxidative status, and bioelements levels in patients with TC. The study enrolled 52 patients with TC and 61 healthy volunteers. Toxic metals and bioelements levels were analyzed by atomic absorption spectrophotometry (AAS) while electrochemiluminescence immunoassay (ECLIA) and spectrophotometry methods were used for hormone and oxidative parameters evaluation. Significantly higher blood Cd levels were depicted in TC cohort. Furthermore, blood Cd elevation was associated with a 1.98 higher probability of TC developing. However, a metal concentration between healthy and tumor testis tissue did not differ significantly. Lower levels of estradiol and testosterone, established in a cohort of TC patients, followed the significant role of hormones in TC development. At the same time, ischemia-modified albumin (IMA) has been recognized as a parameter with very good accuracy as a potential diagnostic marker for TC. The study revealed different distribution patterns of copper (Cu) and zinc (Zn) in the three compartments of the patients, as well significant correlation between essential metals Cu/Zn and toxic metals Cd/Pb indicating metal-metal interactions as pivotal mechanisms of metals toxicity.",
publisher = "Elsevier Ltd",
journal = "Chemosphere",
title = "Cadmium and lead implication in testis cancer; is there a connection?",
volume = "330",
doi = "10.1016/j.chemosphere.2023.138698"
}
Anđelković, M., Buha-Đorđević, A., Vukelić, D., Đukić-Ćosić, D., Aćimović, M., Bojanić, N., Bartolović, D., Bulat, P., Antonijević, B.,& Bulat, Z.. (2023). Cadmium and lead implication in testis cancer; is there a connection?. in Chemosphere
Elsevier Ltd., 330.
https://doi.org/10.1016/j.chemosphere.2023.138698
Anđelković M, Buha-Đorđević A, Vukelić D, Đukić-Ćosić D, Aćimović M, Bojanić N, Bartolović D, Bulat P, Antonijević B, Bulat Z. Cadmium and lead implication in testis cancer; is there a connection?. in Chemosphere. 2023;330.
doi:10.1016/j.chemosphere.2023.138698 .
Anđelković, Milena, Buha-Đorđević, Aleksandra, Vukelić, Dragana, Đukić-Ćosić, Danijela, Aćimović, Miodrag, Bojanić, Nebojša, Bartolović, Daniela, Bulat, Petar, Antonijević, Biljana, Bulat, Zorica, "Cadmium and lead implication in testis cancer; is there a connection?" in Chemosphere, 330 (2023),
https://doi.org/10.1016/j.chemosphere.2023.138698 . .
2

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Vukelić, Dragana; Buha-Đorđević, Aleksandra; Anđelković, Milena; Antonijević-Miljaković, Evica; Baralić, Katarina; Živančević, Katarina; Bulat, Petar; Radovanović, Jelena; Đukić-Ćosić, Danijela; Antonijević, Biljana; Bulat, Zorica

(MDPI, 2023)

TY  - JOUR
AU  - Vukelić, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Anđelković, Milena
AU  - Antonijević-Miljaković, Evica
AU  - Baralić, Katarina
AU  - Živančević, Katarina
AU  - Bulat, Petar
AU  - Radovanović, Jelena
AU  - Đukić-Ćosić, Danijela
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4650
AB  - Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simulate low-dose Pb exposure in an animal model with the aim of assessing oxidative status and essential element levels as the main mechanism of Pb toxicity in the liver and kidneys. Furthermore, dose–response modelling was performed in order to determine the benchmark dose (BMD). Forty-two male Wistar rats were divided into seven groups: one control group, and six groups treated for 28 days with 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg b.w./day, respectively. Oxidative status parameters (superoxide dismutase activity (SOD), superoxide anion radical (O2−), malondialdehyde (MDA), total sulfhydryl groups (SHG), and advanced oxidation protein products (AOPP)) and Pb, copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels were measured. Lowering Cu levels (BMD: 2.7 ng/kg b.w./day), raising AOPP levels (BMD: 0.25 µg/kg b.w./day) in the liver, and inhibiting SOD (BMD: 1.3 ng/kg b.w./day) in the kidneys appear to be the main mechanisms of Pb toxicity. The lowest BMD was derived for a decrease in Cu levels in liver, indicating that this effect is the most sensitive.
PB  - MDPI
T2  - Toxics
T1  - Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats
VL  - 11
IS  - 3
DO  - 10.3390/toxics11030256
ER  - 
@article{
author = "Vukelić, Dragana and Buha-Đorđević, Aleksandra and Anđelković, Milena and Antonijević-Miljaković, Evica and Baralić, Katarina and Živančević, Katarina and Bulat, Petar and Radovanović, Jelena and Đukić-Ćosić, Danijela and Antonijević, Biljana and Bulat, Zorica",
year = "2023",
abstract = "Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simulate low-dose Pb exposure in an animal model with the aim of assessing oxidative status and essential element levels as the main mechanism of Pb toxicity in the liver and kidneys. Furthermore, dose–response modelling was performed in order to determine the benchmark dose (BMD). Forty-two male Wistar rats were divided into seven groups: one control group, and six groups treated for 28 days with 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg b.w./day, respectively. Oxidative status parameters (superoxide dismutase activity (SOD), superoxide anion radical (O2−), malondialdehyde (MDA), total sulfhydryl groups (SHG), and advanced oxidation protein products (AOPP)) and Pb, copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels were measured. Lowering Cu levels (BMD: 2.7 ng/kg b.w./day), raising AOPP levels (BMD: 0.25 µg/kg b.w./day) in the liver, and inhibiting SOD (BMD: 1.3 ng/kg b.w./day) in the kidneys appear to be the main mechanisms of Pb toxicity. The lowest BMD was derived for a decrease in Cu levels in liver, indicating that this effect is the most sensitive.",
publisher = "MDPI",
journal = "Toxics",
title = "Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats",
volume = "11",
number = "3",
doi = "10.3390/toxics11030256"
}
Vukelić, D., Buha-Đorđević, A., Anđelković, M., Antonijević-Miljaković, E., Baralić, K., Živančević, K., Bulat, P., Radovanović, J., Đukić-Ćosić, D., Antonijević, B.,& Bulat, Z.. (2023). Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats. in Toxics
MDPI., 11(3).
https://doi.org/10.3390/toxics11030256
Vukelić D, Buha-Đorđević A, Anđelković M, Antonijević-Miljaković E, Baralić K, Živančević K, Bulat P, Radovanović J, Đukić-Ćosić D, Antonijević B, Bulat Z. Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats. in Toxics. 2023;11(3).
doi:10.3390/toxics11030256 .
Vukelić, Dragana, Buha-Đorđević, Aleksandra, Anđelković, Milena, Antonijević-Miljaković, Evica, Baralić, Katarina, Živančević, Katarina, Bulat, Petar, Radovanović, Jelena, Đukić-Ćosić, Danijela, Antonijević, Biljana, Bulat, Zorica, "Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats" in Toxics, 11, no. 3 (2023),
https://doi.org/10.3390/toxics11030256 . .
2
2

Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats

Vukelić, Dragana; Buha-Đorđević, Aleksandra; Anđelković, Milena; Repić, Aleksandra; Baralić, Katarina; Ćurčić, Marijana; Đukić-Ćosić, Danijela; Boričić, Novica; Antonijević, Biljana; Bulat, Zorica

(Elsevier Ireland Ltd, 2023)

TY  - JOUR
AU  - Vukelić, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Anđelković, Milena
AU  - Repić, Aleksandra
AU  - Baralić, Katarina
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Boričić, Novica
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4385
AB  - The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17–6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004–19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.
PB  - Elsevier Ireland Ltd
T2  - Toxicology Letters
T1  - Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats
VL  - 375
SP  - 69
EP  - 76
DO  - 10.1016/j.toxlet.2023.01.001
ER  - 
@article{
author = "Vukelić, Dragana and Buha-Đorđević, Aleksandra and Anđelković, Milena and Repić, Aleksandra and Baralić, Katarina and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Boričić, Novica and Antonijević, Biljana and Bulat, Zorica",
year = "2023",
abstract = "The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17–6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004–19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.",
publisher = "Elsevier Ireland Ltd",
journal = "Toxicology Letters",
title = "Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats",
volume = "375",
pages = "69-76",
doi = "10.1016/j.toxlet.2023.01.001"
}
Vukelić, D., Buha-Đorđević, A., Anđelković, M., Repić, A., Baralić, K., Ćurčić, M., Đukić-Ćosić, D., Boričić, N., Antonijević, B.,& Bulat, Z.. (2023). Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats. in Toxicology Letters
Elsevier Ireland Ltd., 375, 69-76.
https://doi.org/10.1016/j.toxlet.2023.01.001
Vukelić D, Buha-Đorđević A, Anđelković M, Repić A, Baralić K, Ćurčić M, Đukić-Ćosić D, Boričić N, Antonijević B, Bulat Z. Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats. in Toxicology Letters. 2023;375:69-76.
doi:10.1016/j.toxlet.2023.01.001 .
Vukelić, Dragana, Buha-Đorđević, Aleksandra, Anđelković, Milena, Repić, Aleksandra, Baralić, Katarina, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Boričić, Novica, Antonijević, Biljana, Bulat, Zorica, "Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats" in Toxicology Letters, 375 (2023):69-76,
https://doi.org/10.1016/j.toxlet.2023.01.001 . .
4
3

Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia

Gladović, Ana; Petrović, Bojana; Vukelić, Dragana; Buha-Đorđević, Aleksandra; Ćurčić, Marijana; Đukić-Ćosić, Danijela; Šoštarić, Andrej; Antonijević, Biljana; Bulat, Zorica

(Springer Nature, 2023)

TY  - JOUR
AU  - Gladović, Ana
AU  - Petrović, Bojana
AU  - Vukelić, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Šoštarić, Andrej
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4582
AB  - With global urbanization and industrialization, air pollution has become an inevitable problem. Among air pollutants, toxic metals bound to particulate matter (PM) have a high hazardous potential, contributing to the development of several diseases, including various types of cancer. Due to PM pollution, Serbia is considered to be among the most polluted countries in Europe. Therefore, the objective of the study was to assess and characterize the non-carcinogenic and carcinogenic risks of children’s and adults’ exposure to metal(oid)s (Pb, Cd, Ni, and As) bound to PM10 in five of the most polluted areas in the Republic of Serbia (Subotica, Smederevo, Bor, Valjevo, and Kraljevo). Non-carcinogenic (HQ and HI) and carcinogenic risk (CR) were calculated using USEPA methodology. Our results show that PM10 concentrations exceeded the annual limit of 40 μg/m3 at four out of five monitoring sites (ranging from 44.33 to 63.25 μg/m3). Results obtained from Bor monitoring station show that safe limits were exceeded for both children and adults, indicating an unacceptable risk (> 1) obtained for inhalation exposure to the As (HQ = 6.14) and Cd (HQ = 1.17), while total HI was 7.43, which characterized the risk as unacceptable. For the same station, the CR value was 1.44E−04 (> 1 × 10−4). In other sites, the risks were acceptable. The characterized risk from exposure to the toxic elements via PM10 in critical locations in Serbia contributes to improving air quality by requiring regulatory organs to take new actions and adopt new measures to reduce air pollution.
PB  - Springer Nature
T2  - Environmental Science and Pollution Research
T1  - Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia
VL  - 30
IS  - 22
SP  - 61753
EP  - 61765
DO  - 10.1007/s11356-023-26375-w
ER  - 
@article{
author = "Gladović, Ana and Petrović, Bojana and Vukelić, Dragana and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Šoštarić, Andrej and Antonijević, Biljana and Bulat, Zorica",
year = "2023",
abstract = "With global urbanization and industrialization, air pollution has become an inevitable problem. Among air pollutants, toxic metals bound to particulate matter (PM) have a high hazardous potential, contributing to the development of several diseases, including various types of cancer. Due to PM pollution, Serbia is considered to be among the most polluted countries in Europe. Therefore, the objective of the study was to assess and characterize the non-carcinogenic and carcinogenic risks of children’s and adults’ exposure to metal(oid)s (Pb, Cd, Ni, and As) bound to PM10 in five of the most polluted areas in the Republic of Serbia (Subotica, Smederevo, Bor, Valjevo, and Kraljevo). Non-carcinogenic (HQ and HI) and carcinogenic risk (CR) were calculated using USEPA methodology. Our results show that PM10 concentrations exceeded the annual limit of 40 μg/m3 at four out of five monitoring sites (ranging from 44.33 to 63.25 μg/m3). Results obtained from Bor monitoring station show that safe limits were exceeded for both children and adults, indicating an unacceptable risk (> 1) obtained for inhalation exposure to the As (HQ = 6.14) and Cd (HQ = 1.17), while total HI was 7.43, which characterized the risk as unacceptable. For the same station, the CR value was 1.44E−04 (> 1 × 10−4). In other sites, the risks were acceptable. The characterized risk from exposure to the toxic elements via PM10 in critical locations in Serbia contributes to improving air quality by requiring regulatory organs to take new actions and adopt new measures to reduce air pollution.",
publisher = "Springer Nature",
journal = "Environmental Science and Pollution Research",
title = "Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia",
volume = "30",
number = "22",
pages = "61753-61765",
doi = "10.1007/s11356-023-26375-w"
}
Gladović, A., Petrović, B., Vukelić, D., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D., Šoštarić, A., Antonijević, B.,& Bulat, Z.. (2023). Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia. in Environmental Science and Pollution Research
Springer Nature., 30(22), 61753-61765.
https://doi.org/10.1007/s11356-023-26375-w
Gladović A, Petrović B, Vukelić D, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Šoštarić A, Antonijević B, Bulat Z. Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia. in Environmental Science and Pollution Research. 2023;30(22):61753-61765.
doi:10.1007/s11356-023-26375-w .
Gladović, Ana, Petrović, Bojana, Vukelić, Dragana, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Šoštarić, Andrej, Antonijević, Biljana, Bulat, Zorica, "Carcinogenic and human health risk assessment of children’s and adults’ exposure to toxic metal(oid)s from air PM10 in critical sites of the Republic of Serbia" in Environmental Science and Pollution Research, 30, no. 22 (2023):61753-61765,
https://doi.org/10.1007/s11356-023-26375-w . .

Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells

Božić, Dragica; Živančević, Katarina; Baralić, Katarina; Antonijević-Miljaković, Evica; Buha-Đorđević, Aleksandra; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(Elsevier, 2023)

TY  - JOUR
AU  - Božić, Dragica
AU  - Živančević, Katarina
AU  - Baralić, Katarina
AU  - Antonijević-Miljaković, Evica
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4425
AB  - Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties. However, its toxicity profile and potential to cause adverse effects remain largely unidentified. Thus, this study aimed to generate SFN-triggered adverse outcome pathway (AOP) by looking at the relationship between SFN-chemical structure and its toxicity, as well as SFN-gene interactions. Quantitative structure-activity relationship (QSAR) analysis identified 2 toxophores (Derek Nexus software) that have the potential to cause chromosomal damage and skin sensitization in mammals or mutagenicity in bacteria. Data extracted from Comparative Toxicogenomics Database (CTD) linked SFN with previously proposed outcomes via gene interactions. The total of 11 and 146 genes connected SFN with chromosomal damage and skin diseases, respectively. However, network analysis (NetworkAnalyst tool) revealed that these genes function in wider networks containing 490 and 1986 nodes, respectively. The over-representation analysis (ExpressAnalyst tool) pointed out crucial biological pathways regulated by SFN-interfering genes. These pathways are uploaded to AOP-helpFinder tool which found the 2321 connections between 19 enriched pathways and SFN which were further considered as key events. Two major, interconnected AOPs were generated: first starting from disruption of biological pathways involved in cell cycle and cell proliferation leading to increased apoptosis, and the second one connecting activated immune system signaling pathways to inflammation and apoptosis. In both cases, chromosomal damage and/or skin diseases such as dermatitis or psoriasis appear as adverse outcomes.
PB  - Elsevier
T2  - Biomedicine and Pharmacotherapy
T1  - Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells
VL  - 160
DO  - 10.1016/j.biopha.2023.114316
ER  - 
@article{
author = "Božić, Dragica and Živančević, Katarina and Baralić, Katarina and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties. However, its toxicity profile and potential to cause adverse effects remain largely unidentified. Thus, this study aimed to generate SFN-triggered adverse outcome pathway (AOP) by looking at the relationship between SFN-chemical structure and its toxicity, as well as SFN-gene interactions. Quantitative structure-activity relationship (QSAR) analysis identified 2 toxophores (Derek Nexus software) that have the potential to cause chromosomal damage and skin sensitization in mammals or mutagenicity in bacteria. Data extracted from Comparative Toxicogenomics Database (CTD) linked SFN with previously proposed outcomes via gene interactions. The total of 11 and 146 genes connected SFN with chromosomal damage and skin diseases, respectively. However, network analysis (NetworkAnalyst tool) revealed that these genes function in wider networks containing 490 and 1986 nodes, respectively. The over-representation analysis (ExpressAnalyst tool) pointed out crucial biological pathways regulated by SFN-interfering genes. These pathways are uploaded to AOP-helpFinder tool which found the 2321 connections between 19 enriched pathways and SFN which were further considered as key events. Two major, interconnected AOPs were generated: first starting from disruption of biological pathways involved in cell cycle and cell proliferation leading to increased apoptosis, and the second one connecting activated immune system signaling pathways to inflammation and apoptosis. In both cases, chromosomal damage and/or skin diseases such as dermatitis or psoriasis appear as adverse outcomes.",
publisher = "Elsevier",
journal = "Biomedicine and Pharmacotherapy",
title = "Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells",
volume = "160",
doi = "10.1016/j.biopha.2023.114316"
}
Božić, D., Živančević, K., Baralić, K., Antonijević-Miljaković, E., Buha-Đorđević, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells. in Biomedicine and Pharmacotherapy
Elsevier., 160.
https://doi.org/10.1016/j.biopha.2023.114316
Božić D, Živančević K, Baralić K, Antonijević-Miljaković E, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells. in Biomedicine and Pharmacotherapy. 2023;160.
doi:10.1016/j.biopha.2023.114316 .
Božić, Dragica, Živančević, Katarina, Baralić, Katarina, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells" in Biomedicine and Pharmacotherapy, 160 (2023),
https://doi.org/10.1016/j.biopha.2023.114316 . .
1
3
1

Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study

Baralić, Katarina; Živančević, Katarina; Marić, Đurđica; Božić, Dragica; Buha-Đorđević, Aleksandra; Antonijević-Miljaković, Evica; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(Academic Press Inc., 2023)

TY  - JOUR
AU  - Baralić, Katarina
AU  - Živančević, Katarina
AU  - Marić, Đurđica
AU  - Božić, Dragica
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4651
AB  - Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 – ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susceptibility, but has been shown to act as a friend or a foe depending on various factors. By conducting the mechanistic toxicogenomic data mining approach, this research aimed to determine if SFN can alleviate toxic-metal and/or phthalate/BPA mixture-induced CRC at the gene level. Comparative Toxicogenomics Database, ToppGene Suite portal, Cytoscape software, InteractiVenn and Gene Expression Omnibus (GEO) database (GEO2R tool) was used. Among the mutual genes for all the investigated substances, SFN had a protective impact only through PTGS2. Other proposed protective SFN-targets included ABCA1, ALDH2, BMP2, DPYD, MYC, SLCO2A1, and SOD2, only in the case of phthalates/BPA exposure. The only additional gene relevant for SFN protection against the toxic metal mixture-induced CRC was ABCB1. Additionally, the majority of the top 15 molecular pathways extracted for SFN impact on phthalate and BPA mixture-linked CRC development were directly linked with cancer development, which was not the case with the toxic metal mixture. The current research has indicated that SFN is a more effective chemoprotective agent against CRC induced by phthalates/BPA mixture than by toxic-metal mixture. It has also presented the value of computational methods as a simple tool for directing further research, selecting appropriate biomarkers and exploring the mechanisms of toxicity.
PB  - Academic Press Inc.
T2  - Environmental Research
T1  - Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study
VL  - 227
DO  - 10.1016/j.envres.2023.115818
ER  - 
@article{
author = "Baralić, Katarina and Živančević, Katarina and Marić, Đurđica and Božić, Dragica and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 – ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susceptibility, but has been shown to act as a friend or a foe depending on various factors. By conducting the mechanistic toxicogenomic data mining approach, this research aimed to determine if SFN can alleviate toxic-metal and/or phthalate/BPA mixture-induced CRC at the gene level. Comparative Toxicogenomics Database, ToppGene Suite portal, Cytoscape software, InteractiVenn and Gene Expression Omnibus (GEO) database (GEO2R tool) was used. Among the mutual genes for all the investigated substances, SFN had a protective impact only through PTGS2. Other proposed protective SFN-targets included ABCA1, ALDH2, BMP2, DPYD, MYC, SLCO2A1, and SOD2, only in the case of phthalates/BPA exposure. The only additional gene relevant for SFN protection against the toxic metal mixture-induced CRC was ABCB1. Additionally, the majority of the top 15 molecular pathways extracted for SFN impact on phthalate and BPA mixture-linked CRC development were directly linked with cancer development, which was not the case with the toxic metal mixture. The current research has indicated that SFN is a more effective chemoprotective agent against CRC induced by phthalates/BPA mixture than by toxic-metal mixture. It has also presented the value of computational methods as a simple tool for directing further research, selecting appropriate biomarkers and exploring the mechanisms of toxicity.",
publisher = "Academic Press Inc.",
journal = "Environmental Research",
title = "Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study",
volume = "227",
doi = "10.1016/j.envres.2023.115818"
}
Baralić, K., Živančević, K., Marić, Đ., Božić, D., Buha-Đorđević, A., Antonijević-Miljaković, E., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study. in Environmental Research
Academic Press Inc.., 227.
https://doi.org/10.1016/j.envres.2023.115818
Baralić K, Živančević K, Marić Đ, Božić D, Buha-Đorđević A, Antonijević-Miljaković E, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study. in Environmental Research. 2023;227.
doi:10.1016/j.envres.2023.115818 .
Baralić, Katarina, Živančević, Katarina, Marić, Đurđica, Božić, Dragica, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level – Colorectal carcinoma case study" in Environmental Research, 227 (2023),
https://doi.org/10.1016/j.envres.2023.115818 . .
2

In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether

Radović, Biljana; Stojilković, Nikola; Ćurčić, Marijana; Antonijević-Miljaković, Evica; Buha-Đorđević, Aleksandra; Vukelić-Javorac, Dragana; Baralić, Katarina; Đukić-Ćosić, Danijela; Bulat, Zorica; Antonijević, Biljana

(Elsevier Ireland Ltd, 2023)

TY  - JOUR
AU  - Radović, Biljana
AU  - Stojilković, Nikola
AU  - Ćurčić, Marijana
AU  - Antonijević-Miljaković, Evica
AU  - Buha-Đorđević, Aleksandra
AU  - Vukelić-Javorac, Dragana
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4613
AB  - The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms – oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.
PB  - Elsevier Ireland Ltd
T2  - Toxicology
T1  - In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether
VL  - 489
DO  - 10.1016/j.tox.2023.153496
ER  - 
@article{
author = "Radović, Biljana and Stojilković, Nikola and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Vukelić-Javorac, Dragana and Baralić, Katarina and Đukić-Ćosić, Danijela and Bulat, Zorica and Antonijević, Biljana",
year = "2023",
abstract = "The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms – oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.",
publisher = "Elsevier Ireland Ltd",
journal = "Toxicology",
title = "In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether",
volume = "489",
doi = "10.1016/j.tox.2023.153496"
}
Radović, B., Stojilković, N., Ćurčić, M., Antonijević-Miljaković, E., Buha-Đorđević, A., Vukelić-Javorac, D., Baralić, K., Đukić-Ćosić, D., Bulat, Z.,& Antonijević, B.. (2023). In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether. in Toxicology
Elsevier Ireland Ltd., 489.
https://doi.org/10.1016/j.tox.2023.153496
Radović B, Stojilković N, Ćurčić M, Antonijević-Miljaković E, Buha-Đorđević A, Vukelić-Javorac D, Baralić K, Đukić-Ćosić D, Bulat Z, Antonijević B. In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether. in Toxicology. 2023;489.
doi:10.1016/j.tox.2023.153496 .
Radović, Biljana, Stojilković, Nikola, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Vukelić-Javorac, Dragana, Baralić, Katarina, Đukić-Ćosić, Danijela, Bulat, Zorica, Antonijević, Biljana, "In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether" in Toxicology, 489 (2023),
https://doi.org/10.1016/j.tox.2023.153496 . .
1
1

Exploring the endocrine disrupting potential of lead through benchmark modelling – Study in humans

Javorac, Dragana; Baralić, Katarina; Marić, Đurđica; Mandić-Rajčević, Stefan; Đukić-Ćosić, Danijela; Bulat, Zorica; Buha-Đorđević, Aleksandra

(Elsevier Ltd, 2023)

TY  - JOUR
AU  - Javorac, Dragana
AU  - Baralić, Katarina
AU  - Marić, Đurđica
AU  - Mandić-Rajčević, Stefan
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4299
AB  - Exposure to low levels of a toxic metal lead (Pb) affects human health, and its effect as an endocrine disruptor has been reported. However, the precise role of Pb in endocrine health is still unclear because no dose-response relationship has been established for such an effect. The present study aimed to examine blood Pb levels (BLLs) in relation to serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and insulin in 435 nonoccupationally exposed Serbian subjects (218 women, 217 men, 18–94 years of age, mean age 48). In addition, benchmark dose (BMD) values were calculated for these endocrine endpoints using the PROAST 70.1 software. An explicit dose-response dependency between BLL and TSH, fT3, fT4, testosterone, and insulin serum levels was evident from BMD modelling. The results support the positive association between BLLs and serum insulin levels, with observed dose-response and calculated BMD values of 1.49 and 0.74 μg Pb/dL in males and females, respectively. Collectively, our findings reported potential endocrine-disrupting effects of Pb at the environmental exposure levels experienced by current Serbian population. They also strengthen the notion that the blood Pb threshold level for an endocrine effect is low.
PB  - Elsevier Ltd
T2  - Environmental Pollution
T1  - Exploring the endocrine disrupting potential of lead through benchmark
modelling – Study in humans
VL  - 316
DO  - 10.1016/j.envpol.2022.120428
ER  - 
@article{
author = "Javorac, Dragana and Baralić, Katarina and Marić, Đurđica and Mandić-Rajčević, Stefan and Đukić-Ćosić, Danijela and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Exposure to low levels of a toxic metal lead (Pb) affects human health, and its effect as an endocrine disruptor has been reported. However, the precise role of Pb in endocrine health is still unclear because no dose-response relationship has been established for such an effect. The present study aimed to examine blood Pb levels (BLLs) in relation to serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and insulin in 435 nonoccupationally exposed Serbian subjects (218 women, 217 men, 18–94 years of age, mean age 48). In addition, benchmark dose (BMD) values were calculated for these endocrine endpoints using the PROAST 70.1 software. An explicit dose-response dependency between BLL and TSH, fT3, fT4, testosterone, and insulin serum levels was evident from BMD modelling. The results support the positive association between BLLs and serum insulin levels, with observed dose-response and calculated BMD values of 1.49 and 0.74 μg Pb/dL in males and females, respectively. Collectively, our findings reported potential endocrine-disrupting effects of Pb at the environmental exposure levels experienced by current Serbian population. They also strengthen the notion that the blood Pb threshold level for an endocrine effect is low.",
publisher = "Elsevier Ltd",
journal = "Environmental Pollution",
title = "Exploring the endocrine disrupting potential of lead through benchmark
modelling – Study in humans",
volume = "316",
doi = "10.1016/j.envpol.2022.120428"
}
Javorac, D., Baralić, K., Marić, Đ., Mandić-Rajčević, S., Đukić-Ćosić, D., Bulat, Z.,& Buha-Đorđević, A.. (2023). Exploring the endocrine disrupting potential of lead through benchmark
modelling – Study in humans. in Environmental Pollution
Elsevier Ltd., 316.
https://doi.org/10.1016/j.envpol.2022.120428
Javorac D, Baralić K, Marić Đ, Mandić-Rajčević S, Đukić-Ćosić D, Bulat Z, Buha-Đorđević A. Exploring the endocrine disrupting potential of lead through benchmark
modelling – Study in humans. in Environmental Pollution. 2023;316.
doi:10.1016/j.envpol.2022.120428 .
Javorac, Dragana, Baralić, Katarina, Marić, Đurđica, Mandić-Rajčević, Stefan, Đukić-Ćosić, Danijela, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Exploring the endocrine disrupting potential of lead through benchmark
modelling – Study in humans" in Environmental Pollution, 316 (2023),
https://doi.org/10.1016/j.envpol.2022.120428 . .
2
10
7

Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A

Baralić, Katarina; Pavić, Aleksandar; Javorac, Dragana; Živančević, Katarina; Božić, Dragica; Radaković, Nataša; Antonijević-Miljaković, Evica; Buha-Đorđević, Aleksandra; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(Elsevier B.V., 2023)

TY  - JOUR
AU  - Baralić, Katarina
AU  - Pavić, Aleksandar
AU  - Javorac, Dragana
AU  - Živančević, Katarina
AU  - Božić, Dragica
AU  - Radaković, Nataša
AU  - Antonijević-Miljaković, Evica
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4334
AB  - Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).
PB  - Elsevier B.V.
T2  - Journal of Hazardous Materials
T1  - Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A
VL  - 445
DO  - 10.1016/j.jhazmat.2022.130404
ER  - 
@article{
author = "Baralić, Katarina and Pavić, Aleksandar and Javorac, Dragana and Živančević, Katarina and Božić, Dragica and Radaković, Nataša and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).",
publisher = "Elsevier B.V.",
journal = "Journal of Hazardous Materials",
title = "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A",
volume = "445",
doi = "10.1016/j.jhazmat.2022.130404"
}
Baralić, K., Pavić, A., Javorac, D., Živančević, K., Božić, D., Radaković, N., Antonijević-Miljaković, E., Buha-Đorđević, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials
Elsevier B.V.., 445.
https://doi.org/10.1016/j.jhazmat.2022.130404
Baralić K, Pavić A, Javorac D, Živančević K, Božić D, Radaković N, Antonijević-Miljaković E, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials. 2023;445.
doi:10.1016/j.jhazmat.2022.130404 .
Baralić, Katarina, Pavić, Aleksandar, Javorac, Dragana, Živančević, Katarina, Božić, Dragica, Radaković, Nataša, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A" in Journal of Hazardous Materials, 445 (2023),
https://doi.org/10.1016/j.jhazmat.2022.130404 . .
1
3
2

New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model

Buha-Đorđević, Aleksandra; Milovanović, Vesna; Ćurčić, Marijana; Antonijević-Miljaković, Evica; Bulat, Zorica; Đukić-Ćosić, Danijela; Janković, Saša; Vučinić, Slavica; Hayes, Wallace; Antonijević, Biljana

(Elsevier Inc, 2023)

TY  - JOUR
AU  - Buha-Đorđević, Aleksandra
AU  - Milovanović, Vesna
AU  - Ćurčić, Marijana
AU  - Antonijević-Miljaković, Evica
AU  - Bulat, Zorica
AU  - Đukić-Ćosić, Danijela
AU  - Janković, Saša
AU  - Vučinić, Slavica
AU  - Hayes, Wallace
AU  - Antonijević, Biljana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4326
AB  - The present study investigated the effects of PCBs on the rat kidneys with attention given to the determination critical effect dose (CED) using the Benchmark dose (BMD) approach. Male albino Wistar rats (7 animals per group) were given by oral gavage Aroclor 1254 dissolved in corn oil at doses of 0.0, 0.5, 1, 2, 4, 8, or 16 mg/kg b.w./day for 28 days. The PCB nephrotoxicity was manifested by a dose-dependent changes in serum urea levels. The study has also revealed PCB-induced oxidative stress induction in kidneys. The observed nephrotoxic effects can be partly explained by oxidative damage of lipids and proteins in the kidneys due to observed reduced CuZnSOD activity and disturbances in antioxidant protection. Аll the renal oxidative stress parameters showed dependence on PCB oral doses as well as internal, measure kidney PCB levels. Calculated BMDL values were lower than estimated no observed adverse effect levels (NOAEL) based on the study, suggesting the importance of BMD approach use in future risk assessment.
PB  - Elsevier Inc
T2  - Environmental Research
T1  - New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model
VL  - 217
DO  - 10.1016/j.envres.2022.114829
ER  - 
@article{
author = "Buha-Đorđević, Aleksandra and Milovanović, Vesna and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Bulat, Zorica and Đukić-Ćosić, Danijela and Janković, Saša and Vučinić, Slavica and Hayes, Wallace and Antonijević, Biljana",
year = "2023",
abstract = "The present study investigated the effects of PCBs on the rat kidneys with attention given to the determination critical effect dose (CED) using the Benchmark dose (BMD) approach. Male albino Wistar rats (7 animals per group) were given by oral gavage Aroclor 1254 dissolved in corn oil at doses of 0.0, 0.5, 1, 2, 4, 8, or 16 mg/kg b.w./day for 28 days. The PCB nephrotoxicity was manifested by a dose-dependent changes in serum urea levels. The study has also revealed PCB-induced oxidative stress induction in kidneys. The observed nephrotoxic effects can be partly explained by oxidative damage of lipids and proteins in the kidneys due to observed reduced CuZnSOD activity and disturbances in antioxidant protection. Аll the renal oxidative stress parameters showed dependence on PCB oral doses as well as internal, measure kidney PCB levels. Calculated BMDL values were lower than estimated no observed adverse effect levels (NOAEL) based on the study, suggesting the importance of BMD approach use in future risk assessment.",
publisher = "Elsevier Inc",
journal = "Environmental Research",
title = "New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model",
volume = "217",
doi = "10.1016/j.envres.2022.114829"
}
Buha-Đorđević, A., Milovanović, V., Ćurčić, M., Antonijević-Miljaković, E., Bulat, Z., Đukić-Ćosić, D., Janković, S., Vučinić, S., Hayes, W.,& Antonijević, B.. (2023). New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model. in Environmental Research
Elsevier Inc., 217.
https://doi.org/10.1016/j.envres.2022.114829
Buha-Đorđević A, Milovanović V, Ćurčić M, Antonijević-Miljaković E, Bulat Z, Đukić-Ćosić D, Janković S, Vučinić S, Hayes W, Antonijević B. New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model. in Environmental Research. 2023;217.
doi:10.1016/j.envres.2022.114829 .
Buha-Đorđević, Aleksandra, Milovanović, Vesna, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Bulat, Zorica, Đukić-Ćosić, Danijela, Janković, Saša, Vučinić, Slavica, Hayes, Wallace, Antonijević, Biljana, "New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model" in Environmental Research, 217 (2023),
https://doi.org/10.1016/j.envres.2022.114829 . .
1

Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia

Panić, Bojana; Jovanović, Marija; Lukić, Vera; Bulat, Zorica; Vučićević, Katarina; Miljković, Branislava; Milovanović, Srđan

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Panić, Bojana
AU  - Jovanović, Marija
AU  - Lukić, Vera
AU  - Bulat, Zorica
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Milovanović, Srđan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4507
AB  - The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors.
AB  - Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia
T1  - Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom
VL  - 72
IS  - 4 suplement
SP  - S225
EP  - S226
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4507
ER  - 
@conference{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Bulat, Zorica and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2022",
abstract = "The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors., Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia, Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom",
volume = "72",
number = "4 suplement",
pages = "S225-S226",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4507"
}
Panić, B., Jovanović, M., Lukić, V., Bulat, Z., Vučićević, K., Miljković, B.,& Milovanović, S.. (2022). Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507
Panić B, Jovanović M, Lukić V, Bulat Z, Vučićević K, Miljković B, Milovanović S. Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju. 2022;72(4 suplement):S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507 .
Panić, Bojana, Jovanović, Marija, Lukić, Vera, Bulat, Zorica, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S225-S226,
https://hdl.handle.net/21.15107/rcub_farfar_4507 .

Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels

Javorac, Dragana; Baralić, Katarina; Marić, Đurđica; Antonijević-Miljaković, Evica; Anđelković, Milena; Ćurčić, Marijana; Đukić-Ćosić, Danijela; Bulat, Zorica; Antonijević, Biljana; Mandić-Rajčević, Stefan; Aćimović, Miodrag; Buha-Đorđević, Aleksandra

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Javorac, Dragana
AU  - Baralić, Katarina
AU  - Marić, Đurđica
AU  - Antonijević-Miljaković, Evica
AU  - Anđelković, Milena
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Mandić-Rajčević, Stefan
AU  - Aćimović, Miodrag
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4609
AB  - Exposure to lead (Pb) and cadmium (Cd) poses risk to human health. It is known that
these metals have toxic impact on male reproductive system, leading to physiological
disorders and infertility. Limited data indicates the carcinogenic potential of Pb, while Cd has
been recognized as carcinogen. Benchmark dose-effect modeling can be applied to data from
human, animal and ecotoxicological studies with the aim to obtain Benchmark dose (BMD),
starting point in human health risk assessment. The aim of this study was to use Benchmark
modeling to determine the dose-effect relationship between Pb and Cd levels in tissues of
testicular and prostate cancer patients and serum testosterone levels. The study was
conducted at the Clinical Center of Serbia, and included 104 patients with prostate and
testicular cancer. Cd and Pb levels (ng/g) were measured by atomic absorption
spectrophotometry in isolated healthy surrounding and carcinoma-affected tissues.
Testosterone levels (ng/mL) were measured using the chemiluminescence immunoassay
(CLIA) method. Dose-effect modeling was performed using PROAST70.1 software with
continuous data. The dose dependence was obtained between Cd levels in tumor tissue and
testosterone levels (BMD: 0.0024 ng Cd/g, prostate cancer and 0.0038 ng Cd/g, testicular
cancer). Dose dependence was obtained between Cd levels in healthy surrounding tissue and
testosterone levels (BMD: 0.0092 ng Cd/g). No dose dependence was obtained when
modeling Pb levels as a dose. The data from this study indicate a potential link between Cd
and testosterone levels, i.e. potential association of Cd exposure with male reproductive
health.
AB  - Izloženost olovu (Pb) i kadmijumu (Cd) predstavlja rizik po zdravlje ljudi. Poznato je da ovi
metali deluju toksično na muški reproduktivni sistem dovodeći do poremećaja fizioloških
funkcija i neplodnosti. Ograničen broj studija ukazuje na kancerogeni potencijal Pb, dok je Cd
poznatihumani karcinogen. Benchmark modelovanje odnosa doza-efekat se teoretski može
primeniti na podacima iz humanih, animalnih i ekotoksikoloških studija, sa ciljem dobijanja
Benchmark doze (BMD) kao polazne tačke u proceni rizika po zdravlje ljudi. Cilj ovog rada
bio je da se Benchmark modelovanjem utvrdi odnos doza-efekat između nivoa Pb i Cd u
tkivima karcinoma testisa i prostate pacijenata i nivoa testosterona u serumu. Studija je
sprovedena na Kliničkom centru Srbije i uključila je 104 pacijenta sa karcinomom prostate i
testisa. Nivoi Cd i Pb (ng/g) su izmereni metodom atomske apsorpcione spektrofotometrije u
izolovanim zdravim okolonim i karcinomom zahvaćenim tkivima. Nivoi testosterona
(ng/mL) su mereni pomoću metode direktnog kompetitivnog hemiluminiscentnog
imunoeseja (CLIA). Modelovanje odnosa doza-efekat je vršeno pomoću PROAST 70.1
softvera (RIVM, Holandija) uz upotrebu kontinuiranih podataka. Dozna zavisnost je dobijena
između nivoa Cd u tumorskom tkivu i nivoa testosterona gde je BMD vrednost iznosila
0,0024 ng Cd/g (karcinom prostate) i 0,0038 ng Cd/g (karcinom testisa). Dozna zavisnost je
dobijena i za modelovanje odnosa nivoa Cd u zdravom tkivu i testosterona, sa BMD
vrednošću 0,0092 ng Cd/g. Pri modelovanju nivoa Pb nije dobijena dozna zavisnost. Podaci
ove studije ukazuju na potencijalnu vezu između nivoa Cd u tkivu i nivoa testosterona,
ukazujući na efekte izloženosti ovom metalu na muško reproduktivno zdravlje.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels
T1  - Modelovanje odnosa doza‐odgovor između nivoa Pb i Cd u tkivima karcinoma testisa i prostate i nivoa testosterona
VL  - 72
IS  - 4 suplement
SP  - S569
EP  - S570
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4609
ER  - 
@conference{
author = "Javorac, Dragana and Baralić, Katarina and Marić, Đurđica and Antonijević-Miljaković, Evica and Anđelković, Milena and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Bulat, Zorica and Antonijević, Biljana and Mandić-Rajčević, Stefan and Aćimović, Miodrag and Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "Exposure to lead (Pb) and cadmium (Cd) poses risk to human health. It is known that
these metals have toxic impact on male reproductive system, leading to physiological
disorders and infertility. Limited data indicates the carcinogenic potential of Pb, while Cd has
been recognized as carcinogen. Benchmark dose-effect modeling can be applied to data from
human, animal and ecotoxicological studies with the aim to obtain Benchmark dose (BMD),
starting point in human health risk assessment. The aim of this study was to use Benchmark
modeling to determine the dose-effect relationship between Pb and Cd levels in tissues of
testicular and prostate cancer patients and serum testosterone levels. The study was
conducted at the Clinical Center of Serbia, and included 104 patients with prostate and
testicular cancer. Cd and Pb levels (ng/g) were measured by atomic absorption
spectrophotometry in isolated healthy surrounding and carcinoma-affected tissues.
Testosterone levels (ng/mL) were measured using the chemiluminescence immunoassay
(CLIA) method. Dose-effect modeling was performed using PROAST70.1 software with
continuous data. The dose dependence was obtained between Cd levels in tumor tissue and
testosterone levels (BMD: 0.0024 ng Cd/g, prostate cancer and 0.0038 ng Cd/g, testicular
cancer). Dose dependence was obtained between Cd levels in healthy surrounding tissue and
testosterone levels (BMD: 0.0092 ng Cd/g). No dose dependence was obtained when
modeling Pb levels as a dose. The data from this study indicate a potential link between Cd
and testosterone levels, i.e. potential association of Cd exposure with male reproductive
health., Izloženost olovu (Pb) i kadmijumu (Cd) predstavlja rizik po zdravlje ljudi. Poznato je da ovi
metali deluju toksično na muški reproduktivni sistem dovodeći do poremećaja fizioloških
funkcija i neplodnosti. Ograničen broj studija ukazuje na kancerogeni potencijal Pb, dok je Cd
poznatihumani karcinogen. Benchmark modelovanje odnosa doza-efekat se teoretski može
primeniti na podacima iz humanih, animalnih i ekotoksikoloških studija, sa ciljem dobijanja
Benchmark doze (BMD) kao polazne tačke u proceni rizika po zdravlje ljudi. Cilj ovog rada
bio je da se Benchmark modelovanjem utvrdi odnos doza-efekat između nivoa Pb i Cd u
tkivima karcinoma testisa i prostate pacijenata i nivoa testosterona u serumu. Studija je
sprovedena na Kliničkom centru Srbije i uključila je 104 pacijenta sa karcinomom prostate i
testisa. Nivoi Cd i Pb (ng/g) su izmereni metodom atomske apsorpcione spektrofotometrije u
izolovanim zdravim okolonim i karcinomom zahvaćenim tkivima. Nivoi testosterona
(ng/mL) su mereni pomoću metode direktnog kompetitivnog hemiluminiscentnog
imunoeseja (CLIA). Modelovanje odnosa doza-efekat je vršeno pomoću PROAST 70.1
softvera (RIVM, Holandija) uz upotrebu kontinuiranih podataka. Dozna zavisnost je dobijena
između nivoa Cd u tumorskom tkivu i nivoa testosterona gde je BMD vrednost iznosila
0,0024 ng Cd/g (karcinom prostate) i 0,0038 ng Cd/g (karcinom testisa). Dozna zavisnost je
dobijena i za modelovanje odnosa nivoa Cd u zdravom tkivu i testosterona, sa BMD
vrednošću 0,0092 ng Cd/g. Pri modelovanju nivoa Pb nije dobijena dozna zavisnost. Podaci
ove studije ukazuju na potencijalnu vezu između nivoa Cd u tkivu i nivoa testosterona,
ukazujući na efekte izloženosti ovom metalu na muško reproduktivno zdravlje.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels, Modelovanje odnosa doza‐odgovor između nivoa Pb i Cd u tkivima karcinoma testisa i prostate i nivoa testosterona",
volume = "72",
number = "4 suplement",
pages = "S569-S570",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4609"
}
Javorac, D., Baralić, K., Marić, Đ., Antonijević-Miljaković, E., Anđelković, M., Ćurčić, M., Đukić-Ćosić, D., Bulat, Z., Antonijević, B., Mandić-Rajčević, S., Aćimović, M.,& Buha-Đorđević, A.. (2022). Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S569-S570.
https://hdl.handle.net/21.15107/rcub_farfar_4609
Javorac D, Baralić K, Marić Đ, Antonijević-Miljaković E, Anđelković M, Ćurčić M, Đukić-Ćosić D, Bulat Z, Antonijević B, Mandić-Rajčević S, Aćimović M, Buha-Đorđević A. Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels. in Arhiv za farmaciju. 2022;72(4 suplement):S569-S570.
https://hdl.handle.net/21.15107/rcub_farfar_4609 .
Javorac, Dragana, Baralić, Katarina, Marić, Đurđica, Antonijević-Miljaković, Evica, Anđelković, Milena, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Bulat, Zorica, Antonijević, Biljana, Mandić-Rajčević, Stefan, Aćimović, Miodrag, Buha-Đorđević, Aleksandra, "Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S569-S570,
https://hdl.handle.net/21.15107/rcub_farfar_4609 .

Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?

Anđelković, Milena; Buha-Đorđević, Aleksandra; Javorac, Dragana; Baralić, Katarina; Đukić-Ćosić, Danijela; Antonijević, Biljana; Ćurčić, Marijana; Antonijević-Miljaković, Evica; Čolaković, Nataša; Aćimović, Miodrag; Bulat, Zorica

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Anđelković, Milena
AU  - Buha-Đorđević, Aleksandra
AU  - Javorac, Dragana
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Antonijević, Biljana
AU  - Ćurčić, Marijana
AU  - Antonijević-Miljaković, Evica
AU  - Čolaković, Nataša
AU  - Aćimović, Miodrag
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4497
AB  - The endocrine potential of Cd and Pb, an important mechanism of their toxicity, has
been established in certain hormone-dependent cancers (1,2). This study aimed to
determine Cd and Pb levels in blood, tumor and healthy surrounding tissue of patients with
breast, prostate and testis cancer and investigate the correlation of Cd and Pb with sex
hormone levels in the patient's blood. The study involved 55 breast, 41 prostate and 52 testis
cancer patients, while healthy women (41) and men (61) represented control groups.
Electrothermal atomic absorption spectrophotometry was used for Cd and Pb levels
determination. Significantly higher Cd levels, i.e. lower Pb in tumor tissue compared to the
healthy surrounding tissue were found in patients with breast cancer. A positive correlation
was confirmed between Cd levels in the changed tissue and both human gonadotropins, and
a negative correlation with estradiol, as well between Pb in tumor tissue and testosterone
levels. Patients with prostate and testis cancer were characterized by significantly higher
blood Cd levels compared to healthy subjects. Furthermore, significant Cd and Pb tumor
tissue accumulation was shown in prostate and testis cancer patients. A significant positive
correlation was found between blood Cd and estradiol levels in patients with prostate
cancer. The study highlighted higher Cd level as a significant predictor of cancer, and
confirmed impaired sex hormone homeostasis as pivotal mechanism of toxicity underlying
the toxic effects of Cd and Pb in patients with breast, prostate and testis cancer.
AB  - Endokrini potencijal kadmijuma (Cd) i olova (Pb), kao važan mehanizam toksičnosti
oba metala, potvrđen je kod određenih hormon-zavisnih karcinoma (1,2). Ova studija je
imala za cilj da utvrdi koncentracije Cd i Pb u krvi, tumorskom i okolnom zdravom tkivu
pacijenata sa karcinomom dojke, prostate i testisa i ispita korelaciju Cd i Pb sa nivoom polnih
hormona u krvi pacijenata. Obuhvatila je 55 pacijentkinja sa karcinomom dojke, 41 pacijenta
sa karcinomom prostate i 52 pacijenta sa karcinomom testisa, dok su u kontrolnu grupu bile
uključene zdrave žene (41) i zdravi muškarci (61). Koncentracije Cd i Pb su analizirane
elektrotermalnom atomskom apsorpcionom spektrofotometrijom. Značajno više
koncentracije Cd, odnosno niže Pb u tumorskom u odnosu na okolno zdravo tkivo utvrđene
su kod pacijentkinja sa karcinomom dojke. Pozitivna korelacija je potvrđena između
koncentracija Cd u tkivu izmenjene strukture i oba humana gonadotropina, a negativna sa
estradiolom, te između Pb u tumorskom tkivu i testosterona. Pacijente sa karcinomom
prostate i testisa karakterisale su značajno više koncentracije Cd u krvi u odnosu na zdrave
ispitanike, a pokazana je i značajna akumulacija Cd i Pb u tumorskom tkivu prostate i testisa.
Značajna pozitivna korelacija utvrđena je između koncentracije Cd i estradiola u krvi kod
pacijenata sa karcinom prostate. Studija je pokazala da su više koncentracije Cd značajan
prediktor za nastanak karcinoma i potvrdilanarušenu homeostazu polnih hormona kao
važan mehanizam toksičnosti koji se nalazi u osnovi toksičnih efekata Cd i Pb kod obolelih od
karcinoma dojke, prostate i testisa.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?
T1  - Narušena homeostaza polnih hormona kod pacijenata sa karcinom dojke, prostate i testisa: koja je uloga kadmijuma i olova
VL  - 72
IS  - 4 suplement
SP  - S211
EP  - S212
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4497
ER  - 
@conference{
author = "Anđelković, Milena and Buha-Đorđević, Aleksandra and Javorac, Dragana and Baralić, Katarina and Đukić-Ćosić, Danijela and Antonijević, Biljana and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Čolaković, Nataša and Aćimović, Miodrag and Bulat, Zorica",
year = "2022",
abstract = "The endocrine potential of Cd and Pb, an important mechanism of their toxicity, has
been established in certain hormone-dependent cancers (1,2). This study aimed to
determine Cd and Pb levels in blood, tumor and healthy surrounding tissue of patients with
breast, prostate and testis cancer and investigate the correlation of Cd and Pb with sex
hormone levels in the patient's blood. The study involved 55 breast, 41 prostate and 52 testis
cancer patients, while healthy women (41) and men (61) represented control groups.
Electrothermal atomic absorption spectrophotometry was used for Cd and Pb levels
determination. Significantly higher Cd levels, i.e. lower Pb in tumor tissue compared to the
healthy surrounding tissue were found in patients with breast cancer. A positive correlation
was confirmed between Cd levels in the changed tissue and both human gonadotropins, and
a negative correlation with estradiol, as well between Pb in tumor tissue and testosterone
levels. Patients with prostate and testis cancer were characterized by significantly higher
blood Cd levels compared to healthy subjects. Furthermore, significant Cd and Pb tumor
tissue accumulation was shown in prostate and testis cancer patients. A significant positive
correlation was found between blood Cd and estradiol levels in patients with prostate
cancer. The study highlighted higher Cd level as a significant predictor of cancer, and
confirmed impaired sex hormone homeostasis as pivotal mechanism of toxicity underlying
the toxic effects of Cd and Pb in patients with breast, prostate and testis cancer., Endokrini potencijal kadmijuma (Cd) i olova (Pb), kao važan mehanizam toksičnosti
oba metala, potvrđen je kod određenih hormon-zavisnih karcinoma (1,2). Ova studija je
imala za cilj da utvrdi koncentracije Cd i Pb u krvi, tumorskom i okolnom zdravom tkivu
pacijenata sa karcinomom dojke, prostate i testisa i ispita korelaciju Cd i Pb sa nivoom polnih
hormona u krvi pacijenata. Obuhvatila je 55 pacijentkinja sa karcinomom dojke, 41 pacijenta
sa karcinomom prostate i 52 pacijenta sa karcinomom testisa, dok su u kontrolnu grupu bile
uključene zdrave žene (41) i zdravi muškarci (61). Koncentracije Cd i Pb su analizirane
elektrotermalnom atomskom apsorpcionom spektrofotometrijom. Značajno više
koncentracije Cd, odnosno niže Pb u tumorskom u odnosu na okolno zdravo tkivo utvrđene
su kod pacijentkinja sa karcinomom dojke. Pozitivna korelacija je potvrđena između
koncentracija Cd u tkivu izmenjene strukture i oba humana gonadotropina, a negativna sa
estradiolom, te između Pb u tumorskom tkivu i testosterona. Pacijente sa karcinomom
prostate i testisa karakterisale su značajno više koncentracije Cd u krvi u odnosu na zdrave
ispitanike, a pokazana je i značajna akumulacija Cd i Pb u tumorskom tkivu prostate i testisa.
Značajna pozitivna korelacija utvrđena je između koncentracije Cd i estradiola u krvi kod
pacijenata sa karcinom prostate. Studija je pokazala da su više koncentracije Cd značajan
prediktor za nastanak karcinoma i potvrdilanarušenu homeostazu polnih hormona kao
važan mehanizam toksičnosti koji se nalazi u osnovi toksičnih efekata Cd i Pb kod obolelih od
karcinoma dojke, prostate i testisa.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?, Narušena homeostaza polnih hormona kod pacijenata sa karcinom dojke, prostate i testisa: koja je uloga kadmijuma i olova",
volume = "72",
number = "4 suplement",
pages = "S211-S212",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4497"
}
Anđelković, M., Buha-Đorđević, A., Javorac, D., Baralić, K., Đukić-Ćosić, D., Antonijević, B., Ćurčić, M., Antonijević-Miljaković, E., Čolaković, N., Aćimović, M.,& Bulat, Z.. (2022). Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S211-S212.
https://hdl.handle.net/21.15107/rcub_farfar_4497
Anđelković M, Buha-Đorđević A, Javorac D, Baralić K, Đukić-Ćosić D, Antonijević B, Ćurčić M, Antonijević-Miljaković E, Čolaković N, Aćimović M, Bulat Z. Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?. in Arhiv za farmaciju. 2022;72(4 suplement):S211-S212.
https://hdl.handle.net/21.15107/rcub_farfar_4497 .
Anđelković, Milena, Buha-Đorđević, Aleksandra, Javorac, Dragana, Baralić, Katarina, Đukić-Ćosić, Danijela, Antonijević, Biljana, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Čolaković, Nataša, Aćimović, Miodrag, Bulat, Zorica, "Impaired sex hormone homeostasis in patients with breast, prostate and testis cancer: What is the role of cadmium and lead?" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S211-S212,
https://hdl.handle.net/21.15107/rcub_farfar_4497 .

Old lead, new challenges: Is there a safe level of exposure?

Javorac, Dragana; Marić, Đurđica; Baralić, Katarina; Anđelković, Milena; Antonijević-Miljaković, Evica; Buha-Đorđević, Aleksandra; Đukić-Ćosić, Danijela; Ćurčić, Marijana; Antonijević, Biljana; Bulat, Zorica

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Javorac, Dragana
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Anđelković, Milena
AU  - Antonijević-Miljaković, Evica
AU  - Buha-Đorđević, Aleksandra
AU  - Đukić-Ćosić, Danijela
AU  - Ćurčić, Marijana
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4496
AB  - Lead (Pb) is one of the most important toxic metals without known physiological role.
Recent data indicate that any exposure, even low, can be harmful. Therefore, safe blood lead
levels, as well as tolerating daily intake, have not been identified. In adults, the most sensitive
effect is increase in systolic blood pressure, while in children, the most sensitive effect is on
cognition. Therefore, the aim of this study was to examine the effects of low lead doses on the
central nervous and cardiovascular system in a rat model. The study was conducted on
Wistar rats (n = 42; 7 groups) treated for 28 days, with increasing doses of 0.1; 0.5; 1; 3; 7;
15 mgPb/kg b.w./day to simulate real exposure. After the sacrifice, the brain and heart were
isolated, in which the parameters of oxidative status, bioelements and lead levels were
determined. Benchmark modelling of the dose-effect relationship was performed using
PROAST 70.1 software (RIVM, Netherlands). The obtained results indicate that lead leads to
the induction of oxidative stress and dishomeostasis of bioelements. The lowest value of the
Benchmark dose (BMD) was obtained for increase the total oxidative status in the brain
(4.49e-06 mgPb/kg/b.w./day), which is the most sensitive effect. In the case of heart, the
most sensitive effect was increase in malondialdehyde (BMD: 0.000248 mgPb/kg/b.w./day).
Obtained results indicate that low lead doses have toxic effects on heart and brain. Obtained
BMD may be useful in assessing human health risk of low lead dose exposure.
AB  - Olovo (Pb) je jedan od najznačajnijih toksičnih metala bez poznate fiziološke uloge u
organizmu. Novija istraživanja ukazuju da potencijalno svaka izloženost olovu, čak i niskim
dozama, može biti štetna, te tolerišući dnevni unos, kao ni bezbedan nivo u krvi, nisu
utvrđeni. Kod odraslih, kao najosetljiviji efekat izdvaja se povećanje sistolnog krvnog
pritiska, dok je kod dece to poremećaj kognicije. Imajući navedeno u vidu, cilj ove studije bio
je da se na animalnom modelu ispita uticaj niskih doza olova na centralni nervni i
kardiovaskularni sistem, koji su do sada identifikovani kao najosetljiviji na dejstvo olova, i
odrede Benchmark doze (BMD). Studija je sprovedena na modelu Wistar pacova koji su
podeljeni u 7 grupa tretiranih tokom 28 dana rastućim dozama olova 0, 0,1; 0,5; 1; 3; 7; 15
mg Pb/kg t.m./dan kako bi se simulirala realna izloženost. Nakon žrtvovanja pacova,
izolovani su mozak i srce u kojima su određeni olovo, bioelementi i parametri oksidativnog
statusa. Benchmark modelovanje odnosa doza-efekat vršeno je pomoću PROAST 70.1
softvera (RIVM, Holandija). Dobijeni rezultati ukazuju da olovo dovodi do indukcije
oksidativnog stresa i poremećaja homeostaze bioelemenata. Najniža BMD dobijena je za
povećanje totalnog oksidativnog statusa u mozgu (4,49e-06 mg Pb/kg t.m./dan), što
predstavlja najosetljiviji efekat, a u srcu je to povećanje koncentracije malondialdehida
(BMD: 0,000248 mg Pb/kg t.m./dan). Dobijeni rezultati ukazuju da i niske doze olova mogu
ispoljiti toksične efekte na srce i mozak, a dobijene BMD su od značaja za procenu rizika
olova po zdravlje ljudi.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Old lead, new challenges: Is there a safe level of exposure?
T1  - Staro olovo, novi izazovi: postoji li bezbedan nivo izloženosti?
VL  - 72
IS  - 4 suplement
SP  - S209
EP  - S210
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4496
ER  - 
@conference{
author = "Javorac, Dragana and Marić, Đurđica and Baralić, Katarina and Anđelković, Milena and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Đukić-Ćosić, Danijela and Ćurčić, Marijana and Antonijević, Biljana and Bulat, Zorica",
year = "2022",
abstract = "Lead (Pb) is one of the most important toxic metals without known physiological role.
Recent data indicate that any exposure, even low, can be harmful. Therefore, safe blood lead
levels, as well as tolerating daily intake, have not been identified. In adults, the most sensitive
effect is increase in systolic blood pressure, while in children, the most sensitive effect is on
cognition. Therefore, the aim of this study was to examine the effects of low lead doses on the
central nervous and cardiovascular system in a rat model. The study was conducted on
Wistar rats (n = 42; 7 groups) treated for 28 days, with increasing doses of 0.1; 0.5; 1; 3; 7;
15 mgPb/kg b.w./day to simulate real exposure. After the sacrifice, the brain and heart were
isolated, in which the parameters of oxidative status, bioelements and lead levels were
determined. Benchmark modelling of the dose-effect relationship was performed using
PROAST 70.1 software (RIVM, Netherlands). The obtained results indicate that lead leads to
the induction of oxidative stress and dishomeostasis of bioelements. The lowest value of the
Benchmark dose (BMD) was obtained for increase the total oxidative status in the brain
(4.49e-06 mgPb/kg/b.w./day), which is the most sensitive effect. In the case of heart, the
most sensitive effect was increase in malondialdehyde (BMD: 0.000248 mgPb/kg/b.w./day).
Obtained results indicate that low lead doses have toxic effects on heart and brain. Obtained
BMD may be useful in assessing human health risk of low lead dose exposure., Olovo (Pb) je jedan od najznačajnijih toksičnih metala bez poznate fiziološke uloge u
organizmu. Novija istraživanja ukazuju da potencijalno svaka izloženost olovu, čak i niskim
dozama, može biti štetna, te tolerišući dnevni unos, kao ni bezbedan nivo u krvi, nisu
utvrđeni. Kod odraslih, kao najosetljiviji efekat izdvaja se povećanje sistolnog krvnog
pritiska, dok je kod dece to poremećaj kognicije. Imajući navedeno u vidu, cilj ove studije bio
je da se na animalnom modelu ispita uticaj niskih doza olova na centralni nervni i
kardiovaskularni sistem, koji su do sada identifikovani kao najosetljiviji na dejstvo olova, i
odrede Benchmark doze (BMD). Studija je sprovedena na modelu Wistar pacova koji su
podeljeni u 7 grupa tretiranih tokom 28 dana rastućim dozama olova 0, 0,1; 0,5; 1; 3; 7; 15
mg Pb/kg t.m./dan kako bi se simulirala realna izloženost. Nakon žrtvovanja pacova,
izolovani su mozak i srce u kojima su određeni olovo, bioelementi i parametri oksidativnog
statusa. Benchmark modelovanje odnosa doza-efekat vršeno je pomoću PROAST 70.1
softvera (RIVM, Holandija). Dobijeni rezultati ukazuju da olovo dovodi do indukcije
oksidativnog stresa i poremećaja homeostaze bioelemenata. Najniža BMD dobijena je za
povećanje totalnog oksidativnog statusa u mozgu (4,49e-06 mg Pb/kg t.m./dan), što
predstavlja najosetljiviji efekat, a u srcu je to povećanje koncentracije malondialdehida
(BMD: 0,000248 mg Pb/kg t.m./dan). Dobijeni rezultati ukazuju da i niske doze olova mogu
ispoljiti toksične efekte na srce i mozak, a dobijene BMD su od značaja za procenu rizika
olova po zdravlje ljudi.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Old lead, new challenges: Is there a safe level of exposure?, Staro olovo, novi izazovi: postoji li bezbedan nivo izloženosti?",
volume = "72",
number = "4 suplement",
pages = "S209-S210",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4496"
}
Javorac, D., Marić, Đ., Baralić, K., Anđelković, M., Antonijević-Miljaković, E., Buha-Đorđević, A., Đukić-Ćosić, D., Ćurčić, M., Antonijević, B.,& Bulat, Z.. (2022). Old lead, new challenges: Is there a safe level of exposure?. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S209-S210.
https://hdl.handle.net/21.15107/rcub_farfar_4496
Javorac D, Marić Đ, Baralić K, Anđelković M, Antonijević-Miljaković E, Buha-Đorđević A, Đukić-Ćosić D, Ćurčić M, Antonijević B, Bulat Z. Old lead, new challenges: Is there a safe level of exposure?. in Arhiv za farmaciju. 2022;72(4 suplement):S209-S210.
https://hdl.handle.net/21.15107/rcub_farfar_4496 .
Javorac, Dragana, Marić, Đurđica, Baralić, Katarina, Anđelković, Milena, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Đukić-Ćosić, Danijela, Ćurčić, Marijana, Antonijević, Biljana, Bulat, Zorica, "Old lead, new challenges: Is there a safe level of exposure?" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S209-S210,
https://hdl.handle.net/21.15107/rcub_farfar_4496 .

Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study

Baralić, Katarina; Javorac, Dragana; Marić, Đurđica; Đukić-Ćosić, Danijela; Bulat, Zorica; Antonijević-Miljaković, Evica; Anđelković, Milena; Antonijević, Biljana; Aschner, Michael; Buha-Đorđević, Aleksandra

(Elsevier B.V., 2022)

TY  - JOUR
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Marić, Đurđica
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Antonijević-Miljaković, Evica
AU  - Anđelković, Milena
AU  - Antonijević, Biljana
AU  - Aschner, Michael
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4351
AB  - The main objective of this research was to conduct a dose–response modeling between the internal dose of measured blood Cd, As, Hg, Ni, and Cr and hormonal response of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The study included 207 male participants from subjects of 5 different cohorts (patients with prostate, testicular, and pancreatic cancer, patients suffering from various thyroid and metabolic disorders, as well as healthy volunteers), enrolled from January 2019 to May 2021 at the Clinical Centre of Serbia in Belgrade, Serbia. Benchmark dose–response modeling analysis was performed with the PROAST software version 70.1, showing the hormone levels as quantal data. The averaging technique was applied to compute the Benchmark dose (BMD) interval (BMDI), with benchmark response set at 10%. Dose-response relationships between metal/metalloid blood concentration and serum hormone levels were confirmed for all the investigated metals/metalloid and hormones. The narrowest BMDI was found for Cd-testosterone and Hg-LH pairs, indicative of high confidence in these estimates. Although further research is needed, the observed findings demonstrate that the BMD approach may prove to be significant in the dose–response modeling of human data.
PB  - Elsevier B.V.
T2  - Environment International
T1  - Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study
VL  - 165
DO  - 10.1016/j.envint.2022.107313
ER  - 
@article{
author = "Baralić, Katarina and Javorac, Dragana and Marić, Đurđica and Đukić-Ćosić, Danijela and Bulat, Zorica and Antonijević-Miljaković, Evica and Anđelković, Milena and Antonijević, Biljana and Aschner, Michael and Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "The main objective of this research was to conduct a dose–response modeling between the internal dose of measured blood Cd, As, Hg, Ni, and Cr and hormonal response of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The study included 207 male participants from subjects of 5 different cohorts (patients with prostate, testicular, and pancreatic cancer, patients suffering from various thyroid and metabolic disorders, as well as healthy volunteers), enrolled from January 2019 to May 2021 at the Clinical Centre of Serbia in Belgrade, Serbia. Benchmark dose–response modeling analysis was performed with the PROAST software version 70.1, showing the hormone levels as quantal data. The averaging technique was applied to compute the Benchmark dose (BMD) interval (BMDI), with benchmark response set at 10%. Dose-response relationships between metal/metalloid blood concentration and serum hormone levels were confirmed for all the investigated metals/metalloid and hormones. The narrowest BMDI was found for Cd-testosterone and Hg-LH pairs, indicative of high confidence in these estimates. Although further research is needed, the observed findings demonstrate that the BMD approach may prove to be significant in the dose–response modeling of human data.",
publisher = "Elsevier B.V.",
journal = "Environment International",
title = "Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study",
volume = "165",
doi = "10.1016/j.envint.2022.107313"
}
Baralić, K., Javorac, D., Marić, Đ., Đukić-Ćosić, D., Bulat, Z., Antonijević-Miljaković, E., Anđelković, M., Antonijević, B., Aschner, M.,& Buha-Đorđević, A.. (2022). Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study. in Environment International
Elsevier B.V.., 165.
https://doi.org/10.1016/j.envint.2022.107313
Baralić K, Javorac D, Marić Đ, Đukić-Ćosić D, Bulat Z, Antonijević-Miljaković E, Anđelković M, Antonijević B, Aschner M, Buha-Đorđević A. Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study. in Environment International. 2022;165.
doi:10.1016/j.envint.2022.107313 .
Baralić, Katarina, Javorac, Dragana, Marić, Đurđica, Đukić-Ćosić, Danijela, Bulat, Zorica, Antonijević-Miljaković, Evica, Anđelković, Milena, Antonijević, Biljana, Aschner, Michael, Buha-Đorđević, Aleksandra, "Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study" in Environment International, 165 (2022),
https://doi.org/10.1016/j.envint.2022.107313 . .
4
15
11

The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data

Đukić-Ćosić, Danijela; Baralić, Katarina; Javorac, Dragana; Marić, Đurđica; Anđelković, Milena; Ćurčić, Marijana; Repić, Aleksandra; Antonijević, Biljana; Bulat, Zorica; Buha-Đorđević, Aleksandra

(Elsevier B.V., 2022)

TY  - CONF
AU  - Đukić-Ćosić, Danijela
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Marić, Đurđica
AU  - Anđelković, Milena
AU  - Ćurčić, Marijana
AU  - Repić, Aleksandra
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4346
PB  - Elsevier B.V.
C3  - Toxicology Letters
T1  - The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data
VL  - 368
IS  - Supplement
SP  - S277
EP  - S277
DO  - 10.1016/j.toxlet.2022.07.732
ER  - 
@conference{
author = "Đukić-Ćosić, Danijela and Baralić, Katarina and Javorac, Dragana and Marić, Đurđica and Anđelković, Milena and Ćurčić, Marijana and Repić, Aleksandra and Antonijević, Biljana and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2022",
publisher = "Elsevier B.V.",
journal = "Toxicology Letters",
title = "The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data",
volume = "368",
number = "Supplement",
pages = "S277-S277",
doi = "10.1016/j.toxlet.2022.07.732"
}
Đukić-Ćosić, D., Baralić, K., Javorac, D., Marić, Đ., Anđelković, M., Ćurčić, M., Repić, A., Antonijević, B., Bulat, Z.,& Buha-Đorđević, A.. (2022). The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data. in Toxicology Letters
Elsevier B.V.., 368(Supplement), S277-S277.
https://doi.org/10.1016/j.toxlet.2022.07.732
Đukić-Ćosić D, Baralić K, Javorac D, Marić Đ, Anđelković M, Ćurčić M, Repić A, Antonijević B, Bulat Z, Buha-Đorđević A. The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data. in Toxicology Letters. 2022;368(Supplement):S277-S277.
doi:10.1016/j.toxlet.2022.07.732 .
Đukić-Ćosić, Danijela, Baralić, Katarina, Javorac, Dragana, Marić, Đurđica, Anđelković, Milena, Ćurčić, Marijana, Repić, Aleksandra, Antonijević, Biljana, Bulat, Zorica, Buha-Đorđević, Aleksandra, "The linkage between cadmium and insulin resistance - integrating bioinformatics approach with Benchmark modeling of human data" in Toxicology Letters, 368, no. Supplement (2022):S277-S277,
https://doi.org/10.1016/j.toxlet.2022.07.732 . .

Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts

Pizent, Alica; Anđelković, Milena; Tariba Lovaković, Blanka; Živković Semren, Tanja; Buha-Đorđević, Aleksandra; Gamulin, Marija; Bonderović, Vera; Aćimović, Miodrag; Bulat, Zorica

(MDPI, 2022)

TY  - JOUR
AU  - Pizent, Alica
AU  - Anđelković, Milena
AU  - Tariba Lovaković, Blanka
AU  - Živković Semren, Tanja
AU  - Buha-Đorđević, Aleksandra
AU  - Gamulin, Marija
AU  - Bonderović, Vera
AU  - Aćimović, Miodrag
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4301
AB  - We studied the potential role of exposure to various metal(oid)s (As, Cd, Cr, Hg, Ni, and Pb) in prostate cancer. Two cohorts were established: the Croatian cohort, consisting of 62 cases and 30 controls, and the Serbian cohort, consisting of 41 cases and 61 controls. Blood/serum samples were collected. Levels of investigated metal(oid)s, various parameters of oxidative stress, and prostate-specific antigen (PSA) were determined in collected samples. A comparison of the measured parameters between 103 prostate cancer patients and 91 control men from both Croatian and Serbian cohorts showed significantly higher blood Hg, SOD, and GPx levels and significantly lower serum SH levels in prostate cancer patients than in controls. Correlation analyses revealed the significant relationship between certain parameters of oxidative stress and the concentrations of the measured metal(loid)s, pointing to the possible role of metal(oid)-induced oxidative stress imbalance. Furthermore, a significant inverse relationship was found between the blood Pb and the serum PSA in prostate cancer patients, but when the model was adjusted for the impacts of remaining parameters, no significant association between the serum PSA and the measured parameters was found. The results of the overall study indicate a substantial contribution of the measured metal(loid)s to the imbalance of the oxidant/antioxidant system. Although somewhat conflicting, the results of the present study point to the possible role of investigated metal(oid)s in prostate cancer, especially for Hg, since the obtained relationship was observed for both cohorts, followed by the disturbances in oxidative stress status, which were found to be correlated with Hg levels. Nevertheless, further studies in larger cohorts are warranted to explain and confirm the obtained results.
PB  - MDPI
T2  - Antioxidants
T1  - Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts
VL  - 11
IS  - 10
DO  - 10.3390/antiox11102044
ER  - 
@article{
author = "Pizent, Alica and Anđelković, Milena and Tariba Lovaković, Blanka and Živković Semren, Tanja and Buha-Đorđević, Aleksandra and Gamulin, Marija and Bonderović, Vera and Aćimović, Miodrag and Bulat, Zorica",
year = "2022",
abstract = "We studied the potential role of exposure to various metal(oid)s (As, Cd, Cr, Hg, Ni, and Pb) in prostate cancer. Two cohorts were established: the Croatian cohort, consisting of 62 cases and 30 controls, and the Serbian cohort, consisting of 41 cases and 61 controls. Blood/serum samples were collected. Levels of investigated metal(oid)s, various parameters of oxidative stress, and prostate-specific antigen (PSA) were determined in collected samples. A comparison of the measured parameters between 103 prostate cancer patients and 91 control men from both Croatian and Serbian cohorts showed significantly higher blood Hg, SOD, and GPx levels and significantly lower serum SH levels in prostate cancer patients than in controls. Correlation analyses revealed the significant relationship between certain parameters of oxidative stress and the concentrations of the measured metal(loid)s, pointing to the possible role of metal(oid)-induced oxidative stress imbalance. Furthermore, a significant inverse relationship was found between the blood Pb and the serum PSA in prostate cancer patients, but when the model was adjusted for the impacts of remaining parameters, no significant association between the serum PSA and the measured parameters was found. The results of the overall study indicate a substantial contribution of the measured metal(loid)s to the imbalance of the oxidant/antioxidant system. Although somewhat conflicting, the results of the present study point to the possible role of investigated metal(oid)s in prostate cancer, especially for Hg, since the obtained relationship was observed for both cohorts, followed by the disturbances in oxidative stress status, which were found to be correlated with Hg levels. Nevertheless, further studies in larger cohorts are warranted to explain and confirm the obtained results.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts",
volume = "11",
number = "10",
doi = "10.3390/antiox11102044"
}
Pizent, A., Anđelković, M., Tariba Lovaković, B., Živković Semren, T., Buha-Đorđević, A., Gamulin, M., Bonderović, V., Aćimović, M.,& Bulat, Z.. (2022). Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts. in Antioxidants
MDPI., 11(10).
https://doi.org/10.3390/antiox11102044
Pizent A, Anđelković M, Tariba Lovaković B, Živković Semren T, Buha-Đorđević A, Gamulin M, Bonderović V, Aćimović M, Bulat Z. Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts. in Antioxidants. 2022;11(10).
doi:10.3390/antiox11102044 .
Pizent, Alica, Anđelković, Milena, Tariba Lovaković, Blanka, Živković Semren, Tanja, Buha-Đorđević, Aleksandra, Gamulin, Marija, Bonderović, Vera, Aćimović, Miodrag, Bulat, Zorica, "Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts" in Antioxidants, 11, no. 10 (2022),
https://doi.org/10.3390/antiox11102044 . .
3
3

Possible role of lead in breast cancer — a case-control study

Anđelković, Milena; Buha-Đorđević, Aleksandra; Javorac, Dragana; Baralić, Katarina; Đukić-Ćosić, Danijela; Repić, Aleksandra; Zeljković, Aleksandra; Vekić, Jelena; Čolaković, Nataša; Bulat, Zorica

(Springer Nature, 2022)

TY  - JOUR
AU  - Anđelković, Milena
AU  - Buha-Đorđević, Aleksandra
AU  - Javorac, Dragana
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Repić, Aleksandra
AU  - Zeljković, Aleksandra
AU  - Vekić, Jelena
AU  - Čolaković, Nataša
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4103
AB  - Numerous risk factors have been associated with breast cancer (BC), exposure to metalloestrogen, like lead, being such. Since lead involvement in BC is still equivocal, we focused on lead levels in three compartments of BC patients, blood, healthy, and malignant tissues. Also, as the cholesterol role in cancer development was recognized at the beginning of the twentieth century and led to involvement in lipid profile impairment, we further extend our research on lipid profile and enzymes responsible for maintaining lipid balance in BC patients. Fifty-five women diagnosed with BC were enrolled in the study. Forty-one healthy women represented the control group. Lead levels in blood, healthy surrounding and malignant tissue, and lipid profile parameters in serum, were determined. Higher lead levels were obtained in surrounding healthy tissue samples compared to cancerous tissue samples, while blood lead levels of BC women did not differ significantly from the control group. The altered lipid profile scheme in women diagnosed with breast cancer contained significantly higher triglycerides levels (P < 0.001). Moreover, logistic regression analysis revealed triglycerides as a significant predictor of BC (OR = 2.6; P < 0.01). Although statistical significance was missing for lower paraoxonase-1 (PON-1) activities observed in BC women, multivariate logistic regression singled out PON-1 activities as significant BC predictors. The result of the present study further indicated oxidative status imbalance and tissue levels bioelements perturbation. Obtained results in the present study propose possible lead involvement in BC onset accompanied with bioelements redistribution and oxidative stress occurrence.
PB  - Springer Nature
T2  - Environmental Science and Pollution Research
T1  - Possible role of lead in breast cancer — a case-control study
VL  - 29
SP  - 65211
EP  - 65221
DO  - 10.1007/s11356-022-20439-z
ER  - 
@article{
author = "Anđelković, Milena and Buha-Đorđević, Aleksandra and Javorac, Dragana and Baralić, Katarina and Đukić-Ćosić, Danijela and Repić, Aleksandra and Zeljković, Aleksandra and Vekić, Jelena and Čolaković, Nataša and Bulat, Zorica",
year = "2022",
abstract = "Numerous risk factors have been associated with breast cancer (BC), exposure to metalloestrogen, like lead, being such. Since lead involvement in BC is still equivocal, we focused on lead levels in three compartments of BC patients, blood, healthy, and malignant tissues. Also, as the cholesterol role in cancer development was recognized at the beginning of the twentieth century and led to involvement in lipid profile impairment, we further extend our research on lipid profile and enzymes responsible for maintaining lipid balance in BC patients. Fifty-five women diagnosed with BC were enrolled in the study. Forty-one healthy women represented the control group. Lead levels in blood, healthy surrounding and malignant tissue, and lipid profile parameters in serum, were determined. Higher lead levels were obtained in surrounding healthy tissue samples compared to cancerous tissue samples, while blood lead levels of BC women did not differ significantly from the control group. The altered lipid profile scheme in women diagnosed with breast cancer contained significantly higher triglycerides levels (P < 0.001). Moreover, logistic regression analysis revealed triglycerides as a significant predictor of BC (OR = 2.6; P < 0.01). Although statistical significance was missing for lower paraoxonase-1 (PON-1) activities observed in BC women, multivariate logistic regression singled out PON-1 activities as significant BC predictors. The result of the present study further indicated oxidative status imbalance and tissue levels bioelements perturbation. Obtained results in the present study propose possible lead involvement in BC onset accompanied with bioelements redistribution and oxidative stress occurrence.",
publisher = "Springer Nature",
journal = "Environmental Science and Pollution Research",
title = "Possible role of lead in breast cancer — a case-control study",
volume = "29",
pages = "65211-65221",
doi = "10.1007/s11356-022-20439-z"
}
Anđelković, M., Buha-Đorđević, A., Javorac, D., Baralić, K., Đukić-Ćosić, D., Repić, A., Zeljković, A., Vekić, J., Čolaković, N.,& Bulat, Z.. (2022). Possible role of lead in breast cancer — a case-control study. in Environmental Science and Pollution Research
Springer Nature., 29, 65211-65221.
https://doi.org/10.1007/s11356-022-20439-z
Anđelković M, Buha-Đorđević A, Javorac D, Baralić K, Đukić-Ćosić D, Repić A, Zeljković A, Vekić J, Čolaković N, Bulat Z. Possible role of lead in breast cancer — a case-control study. in Environmental Science and Pollution Research. 2022;29:65211-65221.
doi:10.1007/s11356-022-20439-z .
Anđelković, Milena, Buha-Đorđević, Aleksandra, Javorac, Dragana, Baralić, Katarina, Đukić-Ćosić, Danijela, Repić, Aleksandra, Zeljković, Aleksandra, Vekić, Jelena, Čolaković, Nataša, Bulat, Zorica, "Possible role of lead in breast cancer — a case-control study" in Environmental Science and Pollution Research, 29 (2022):65211-65221,
https://doi.org/10.1007/s11356-022-20439-z . .
1
2
2

Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis

Javorac, Dragana; Anđelković, Milena; Repić, Aleksandra; Tatović, Simona; Buha-Đorđević, Aleksandra; Antonijević-Miljaković, Evica; Batinić, Bojan; Boričić, Novica; Đukić-Ćosić, Danijela; Antonijević, Biljana; Bulat, Zorica

(Elsevier Ireland Ltd, 2022)

TY  - JOUR
AU  - Javorac, Dragana
AU  - Anđelković, Milena
AU  - Repić, Aleksandra
AU  - Tatović, Simona
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Batinić, Bojan
AU  - Boričić, Novica
AU  - Đukić-Ćosić, Danijela
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4089
AB  - Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis
VL  - 360
DO  - 10.1016/j.cbi.2022.109932
ER  - 
@article{
author = "Javorac, Dragana and Anđelković, Milena and Repić, Aleksandra and Tatović, Simona and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Batinić, Bojan and Boričić, Novica and Đukić-Ćosić, Danijela and Antonijević, Biljana and Bulat, Zorica",
year = "2022",
abstract = "Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis",
volume = "360",
doi = "10.1016/j.cbi.2022.109932"
}
Javorac, D., Anđelković, M., Repić, A., Tatović, S., Buha-Đorđević, A., Antonijević-Miljaković, E., Batinić, B., Boričić, N., Đukić-Ćosić, D., Antonijević, B.,& Bulat, Z.. (2022). Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 360.
https://doi.org/10.1016/j.cbi.2022.109932
Javorac D, Anđelković M, Repić A, Tatović S, Buha-Đorđević A, Antonijević-Miljaković E, Batinić B, Boričić N, Đukić-Ćosić D, Antonijević B, Bulat Z. Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions. 2022;360.
doi:10.1016/j.cbi.2022.109932 .
Javorac, Dragana, Anđelković, Milena, Repić, Aleksandra, Tatović, Simona, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Batinić, Bojan, Boričić, Novica, Đukić-Ćosić, Danijela, Antonijević, Biljana, Bulat, Zorica, "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis" in Chemico-Biological Interactions, 360 (2022),
https://doi.org/10.1016/j.cbi.2022.109932 . .
4
3

Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling

Javorac, Dragana; Tatović, Simona; Anđelković, Milena; Repić, Aleksandra; Baralić, Katarina; Buha-Đorđević, Aleksandra; Mihajlović, Marija; Kotur-Stevuljević, Jelena; Đukić-Ćosić, Danijela; Ćurčić, Marijana; Antonijević, Biljana; Bulat, Zorica

(Elsevier Ltd, 2022)

TY  - JOUR
AU  - Javorac, Dragana
AU  - Tatović, Simona
AU  - Anđelković, Milena
AU  - Repić, Aleksandra
AU  - Baralić, Katarina
AU  - Buha-Đorđević, Aleksandra
AU  - Mihajlović, Marija
AU  - Kotur-Stevuljević, Jelena
AU  - Đukić-Ćosić, Danijela
AU  - Ćurčić, Marijana
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4046
AB  - Exposure to toxic metals, including lead (Pb), were found as important risk factor for cardiovascular diseases. The aim of the study was to simulate low-level subacute Pb exposure scenario and to determine redox status, redox scores (OXY-score, damage score and protective score) and copper (Cu), zinc (Zn), iron (Fe) and manganese (Mn) levels in cardiac tissue of Wistar rats. Based on the obtained results we have established dose-toxic response relationship and derived Benchmark dose. The male Wistar rats were divided in seven groups (n = 6), six threated groups that received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, by oral gavage and control group. The results of the presented study demonstrated that Pb affect cardiac tissue by inducing production of superoxide anion radical (O2.-) and consequently raising malondialdehyde (MDA) levels. The positive trend in OXY-score and damage score were determined. Effect size analysis showed that the main toxic effects were oxidative damage and elevation of MDA. The lowest BMD was calculated for MDA (2.2e-0.6 mg Pb/kg b.w./day). Obtained BMD may be useful in further assessing point of departure in the human health risks assessment of low-level Pb exposure scenario.
PB  - Elsevier Ltd
T2  - Food and Chemical Toxicology
T1  - Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling
VL  - 161
DO  - 10.1016/j.fct.2022.112825
ER  - 
@article{
author = "Javorac, Dragana and Tatović, Simona and Anđelković, Milena and Repić, Aleksandra and Baralić, Katarina and Buha-Đorđević, Aleksandra and Mihajlović, Marija and Kotur-Stevuljević, Jelena and Đukić-Ćosić, Danijela and Ćurčić, Marijana and Antonijević, Biljana and Bulat, Zorica",
year = "2022",
abstract = "Exposure to toxic metals, including lead (Pb), were found as important risk factor for cardiovascular diseases. The aim of the study was to simulate low-level subacute Pb exposure scenario and to determine redox status, redox scores (OXY-score, damage score and protective score) and copper (Cu), zinc (Zn), iron (Fe) and manganese (Mn) levels in cardiac tissue of Wistar rats. Based on the obtained results we have established dose-toxic response relationship and derived Benchmark dose. The male Wistar rats were divided in seven groups (n = 6), six threated groups that received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, by oral gavage and control group. The results of the presented study demonstrated that Pb affect cardiac tissue by inducing production of superoxide anion radical (O2.-) and consequently raising malondialdehyde (MDA) levels. The positive trend in OXY-score and damage score were determined. Effect size analysis showed that the main toxic effects were oxidative damage and elevation of MDA. The lowest BMD was calculated for MDA (2.2e-0.6 mg Pb/kg b.w./day). Obtained BMD may be useful in further assessing point of departure in the human health risks assessment of low-level Pb exposure scenario.",
publisher = "Elsevier Ltd",
journal = "Food and Chemical Toxicology",
title = "Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling",
volume = "161",
doi = "10.1016/j.fct.2022.112825"
}
Javorac, D., Tatović, S., Anđelković, M., Repić, A., Baralić, K., Buha-Đorđević, A., Mihajlović, M., Kotur-Stevuljević, J., Đukić-Ćosić, D., Ćurčić, M., Antonijević, B.,& Bulat, Z.. (2022). Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling. in Food and Chemical Toxicology
Elsevier Ltd., 161.
https://doi.org/10.1016/j.fct.2022.112825
Javorac D, Tatović S, Anđelković M, Repić A, Baralić K, Buha-Đorđević A, Mihajlović M, Kotur-Stevuljević J, Đukić-Ćosić D, Ćurčić M, Antonijević B, Bulat Z. Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling. in Food and Chemical Toxicology. 2022;161.
doi:10.1016/j.fct.2022.112825 .
Javorac, Dragana, Tatović, Simona, Anđelković, Milena, Repić, Aleksandra, Baralić, Katarina, Buha-Đorđević, Aleksandra, Mihajlović, Marija, Kotur-Stevuljević, Jelena, Đukić-Ćosić, Danijela, Ćurčić, Marijana, Antonijević, Biljana, Bulat, Zorica, "Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling" in Food and Chemical Toxicology, 161 (2022),
https://doi.org/10.1016/j.fct.2022.112825 . .
10
9

Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma

Antunović, Marko; Đorđević, Snežana; Kilibarda, Vesna; Džudović, Jelena; Repić, Aleksandra; Bulat, Zorica

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - JOUR
AU  - Antunović, Marko
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Džudović, Jelena
AU  - Repić, Aleksandra
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4498
AB  - Valproic acid (VPA) is antiepileptic drug with a long history of clinical use,
increasingly applied in the treatment of various diseases (bipolar disorder, migraine
prophylaxis, etc). Due to significant inter-individual differences VPA concentration is often
measured in the purpose of therapeutic drug monitoring (TDM) (1). Acute poisonings with
this drug represent a significant problem. According to the American Association of Poison
Control Centers, there has been VPA poisoning incidence increase in the last 20 years.
Reports from the National Poison Control Center in Belgrade list VPA as one of the three
most common causes of antiepileptic drugs intoxications (2). This paper aimed to develop a
modern analytical method for VPA quantification in patient plasma. UPLC/MS method with
fast and simple sample preparation has been validated. After protein precipitation, VPA was
extracted from 100 μL plasma using HLB cartridges. Caprylic acid solution was used as
internal standard. Chromatographic separation was achieved on C18 column (1.8 μm, 2.1 X
150 mm) with gradient elution at constant mobile phase flow. Good peak resolution was
achieved (Rt VPA - 4.73 min, Rt ISTD - 4.94 min). Validation was performed according European
Medicines Agency recommendations. Based on statistical analysism it was shown that the
method is precise, accurate, specific, sensitive and linearity is confirmed in a wide range of
concentrations (1-250 mg / L). Advantages of this method are simple preparation procedure
from a small amount of sample, without prior derivatization and short duration of analysis,
which fully satisfies the needs of TDM and urgent toxicological analyses.
AB  - Valproinska kiselina (VK) je lek iz grupe antiepileptika sa dugom istorijom kliničke
upotrebe, koji se, osim u terapiji epilepsije, poslednjih decenija sve više koristi u terapiji
različitih bolesti (bipolarni poremećaj, profilaksa migrene itd). Zbog značajnih
interindividualnih varijacija, koncentracija VK se često određuje u svrhe terapijskog praćenja
leka (TDM – Therapeutic Drug Monitoring) (1). S druge strane, akutna trovanja ovim lekom
predstavljaju značajan problem. Prema podacima Američkih centara za kontrolu trovanja
došlo je do povećanja incidence trovanja VK u poslednjih 20 godina, dok izveštaji
Nacionalnog centra za kontrolu trovanja u Beogradu navode VK kao jedan od tri najčešća
uzročnika trovanja kada su u pitanju intoksikacije antiepilepticima (2). Cilj ovoga rada je
razvoj savremene analitičke metode za određivanje koncentracije VK u plazmi pacijenata.
Validovana je UPLC/MS metoda koja podrazumeva brzu i jednostavnu pripremu uzorka.
Nakon precipitacije proteina, izvršena je ekstrakcija iz 100 μL plazme uz pomoć HLB
kertridža. Kao interni standard korišćen je rastvor kaprilne kiseline. Hromatografsko
razdvajanje je postignuto na C18 koloni (1,8 μm, 2,1 X 150 mm) gradijentnim eluiranjem pri
konstantnom protoku mobilne faze. Postignuta je dobra rezolucija pikova (Rt VK - 4,73 min,
Rt ISTD - 4,94 min). Validacija je izvedena prema preporukama Evropske agencije za lekove, a
na osnovu statističke analize je pokazano da je metoda precizna, tačna, specifična, osetljiva i
potvrđena je linearnost u širokom opsegu koncentracija (1-250 mg/L). Prednosti ove
metode su jednostavan način pripreme iz male količine uzorka, bez prethodne derivatizacije,
i kratko vreme trajanja analize, što u potpunosti zadovoljava potrebe TDM-a i urgentnih
toksikoloških analiza.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma
T1  - Razvoj i validacija brze i jednostavne UPLC/MS metode za određivanje terapijskih i toksičnih koncentracija valproinske kiseline u plazmi pacijenata
VL  - 72
IS  - 4 suplement
SP  - S215
EP  - S216
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4498
ER  - 
@article{
author = "Antunović, Marko and Đorđević, Snežana and Kilibarda, Vesna and Džudović, Jelena and Repić, Aleksandra and Bulat, Zorica",
year = "2022",
abstract = "Valproic acid (VPA) is antiepileptic drug with a long history of clinical use,
increasingly applied in the treatment of various diseases (bipolar disorder, migraine
prophylaxis, etc). Due to significant inter-individual differences VPA concentration is often
measured in the purpose of therapeutic drug monitoring (TDM) (1). Acute poisonings with
this drug represent a significant problem. According to the American Association of Poison
Control Centers, there has been VPA poisoning incidence increase in the last 20 years.
Reports from the National Poison Control Center in Belgrade list VPA as one of the three
most common causes of antiepileptic drugs intoxications (2). This paper aimed to develop a
modern analytical method for VPA quantification in patient plasma. UPLC/MS method with
fast and simple sample preparation has been validated. After protein precipitation, VPA was
extracted from 100 μL plasma using HLB cartridges. Caprylic acid solution was used as
internal standard. Chromatographic separation was achieved on C18 column (1.8 μm, 2.1 X
150 mm) with gradient elution at constant mobile phase flow. Good peak resolution was
achieved (Rt VPA - 4.73 min, Rt ISTD - 4.94 min). Validation was performed according European
Medicines Agency recommendations. Based on statistical analysism it was shown that the
method is precise, accurate, specific, sensitive and linearity is confirmed in a wide range of
concentrations (1-250 mg / L). Advantages of this method are simple preparation procedure
from a small amount of sample, without prior derivatization and short duration of analysis,
which fully satisfies the needs of TDM and urgent toxicological analyses., Valproinska kiselina (VK) je lek iz grupe antiepileptika sa dugom istorijom kliničke
upotrebe, koji se, osim u terapiji epilepsije, poslednjih decenija sve više koristi u terapiji
različitih bolesti (bipolarni poremećaj, profilaksa migrene itd). Zbog značajnih
interindividualnih varijacija, koncentracija VK se često određuje u svrhe terapijskog praćenja
leka (TDM – Therapeutic Drug Monitoring) (1). S druge strane, akutna trovanja ovim lekom
predstavljaju značajan problem. Prema podacima Američkih centara za kontrolu trovanja
došlo je do povećanja incidence trovanja VK u poslednjih 20 godina, dok izveštaji
Nacionalnog centra za kontrolu trovanja u Beogradu navode VK kao jedan od tri najčešća
uzročnika trovanja kada su u pitanju intoksikacije antiepilepticima (2). Cilj ovoga rada je
razvoj savremene analitičke metode za određivanje koncentracije VK u plazmi pacijenata.
Validovana je UPLC/MS metoda koja podrazumeva brzu i jednostavnu pripremu uzorka.
Nakon precipitacije proteina, izvršena je ekstrakcija iz 100 μL plazme uz pomoć HLB
kertridža. Kao interni standard korišćen je rastvor kaprilne kiseline. Hromatografsko
razdvajanje je postignuto na C18 koloni (1,8 μm, 2,1 X 150 mm) gradijentnim eluiranjem pri
konstantnom protoku mobilne faze. Postignuta je dobra rezolucija pikova (Rt VK - 4,73 min,
Rt ISTD - 4,94 min). Validacija je izvedena prema preporukama Evropske agencije za lekove, a
na osnovu statističke analize je pokazano da je metoda precizna, tačna, specifična, osetljiva i
potvrđena je linearnost u širokom opsegu koncentracija (1-250 mg/L). Prednosti ove
metode su jednostavan način pripreme iz male količine uzorka, bez prethodne derivatizacije,
i kratko vreme trajanja analize, što u potpunosti zadovoljava potrebe TDM-a i urgentnih
toksikoloških analiza.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma, Razvoj i validacija brze i jednostavne UPLC/MS metode za određivanje terapijskih i toksičnih koncentracija valproinske kiseline u plazmi pacijenata",
volume = "72",
number = "4 suplement",
pages = "S215-S216",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4498"
}
Antunović, M., Đorđević, S., Kilibarda, V., Džudović, J., Repić, A.,& Bulat, Z.. (2022). Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S215-S216.
https://hdl.handle.net/21.15107/rcub_farfar_4498
Antunović M, Đorđević S, Kilibarda V, Džudović J, Repić A, Bulat Z. Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma. in Arhiv za farmaciju. 2022;72(4 suplement):S215-S216.
https://hdl.handle.net/21.15107/rcub_farfar_4498 .
Antunović, Marko, Đorđević, Snežana, Kilibarda, Vesna, Džudović, Jelena, Repić, Aleksandra, Bulat, Zorica, "Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S215-S216,
https://hdl.handle.net/21.15107/rcub_farfar_4498 .

Exposure to mercury and thyroid function: Is there a connection?

Marić, Đurđica; Bonderović, Vera; Javorac, Dragana; Baralić, Katarina; Bulat, Zorica; Đukić-Ćosić, Danijela; Mandić-Rajčević, Stefan; Žarković, Miloš; Buha-Đorđević, Aleksandra

(Beograd : Savez farmaceutskih udruženja Srbije, 2022)

TY  - JOUR
AU  - Marić, Đurđica
AU  - Bonderović, Vera
AU  - Javorac, Dragana
AU  - Baralić, Katarina
AU  - Bulat, Zorica
AU  - Đukić-Ćosić, Danijela
AU  - Mandić-Rajčević, Stefan
AU  - Žarković, Miloš
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4400
AB  - Mercury (Hg) is one of the most important environmental pollutants with endocrine-
disrupting properties. There is little data from epidemiological studies describing the dose-
response relationship between toxic metal levels and hormone levels. The aim of this study was
to use the nearest neighbor matching analysis to determine the difference in Hg concentration in
healthy/sick subjects with thyroid disease and to use Benchmark modeling to determine the dose-
response relationship between Hg levels in the blood and thyroid-stimulating hormone (TSH) and
thyroid hormones in serum. Blood samples were collected and used for Hg measurement using
the ICP-MS method, and separated serum was used for hormone analysis. The study showed the
existence of a statistically significant difference in Hg levels measured in healthy and sick subjects
and the existence of a dose-response relationship between Hg and all measured hormones, with a
narrow interval obtained for the Hg-TSH pair. The results of this research support the use of the
Benchmark dose approach for the purpose of analyzing data from human studies, and our further
research will be focused on examining the impact of low doses on animal models in order to
determine more precise effects of low doses on the organism.
AB  - Živa (Hg) je jedan od najznačajnijih zagađivača životne sredine sa osobinama endokrinog ometača. Malo je podataka iz epidemioloških studija koji opisuju odnos doza-odgovor između nivoa toksičnih metala i nivoa hormona. Cilj ovog rada bio je da primenom nearest neighbor matching analize utvrdi razliku u koncentraciji Hg kod zdravih/obolelih ispitanika od bolesti štitaste žlezde i da primenom Benchmark modelovanja utvrdi odnos doza-odgovor između nivoa Hg u krvi i tireostimulišućeg hormona (TSH) i tiroidnih hormona u serumu. Uzorci krvi su sakupljeni i korišćeni za merenje Hg uz pomoć ICP-MS metode, a izdvojeni serum korišćen je za analizu hormona. Studija je pokazala postojanje statistički značajne razlike u nivoima Hg koji su izmereni kod zdravih i bolesnih ispitanika i postojanje odnosa doza-odgovor između Hg i svih merenih hormona, pri čemu je uzak interval dobijen za Hg-TSH par. Rezultati ovog istraživanja podržavaju upotrebu Benchmark dose pristupa u svrhu analize podataka iz humanih studija, a naša dalja istraživanja će biti usmerena na ispitivanje uticaja niskih doza na životinjskim modelima, u cilju utvrđivanja preciznijih efekata niskih doza na organizam.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Exposure to mercury and thyroid function: Is there a connection?
T1  - Izloženost živi i funkcija štitaste žlezde: postoji li veza?
VL  - 72
IS  - 5
SP  - 468
EP  - 485
DO  - 10.5937/arhfarm72-40122
ER  - 
@article{
author = "Marić, Đurđica and Bonderović, Vera and Javorac, Dragana and Baralić, Katarina and Bulat, Zorica and Đukić-Ćosić, Danijela and Mandić-Rajčević, Stefan and Žarković, Miloš and Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "Mercury (Hg) is one of the most important environmental pollutants with endocrine-
disrupting properties. There is little data from epidemiological studies describing the dose-
response relationship between toxic metal levels and hormone levels. The aim of this study was
to use the nearest neighbor matching analysis to determine the difference in Hg concentration in
healthy/sick subjects with thyroid disease and to use Benchmark modeling to determine the dose-
response relationship between Hg levels in the blood and thyroid-stimulating hormone (TSH) and
thyroid hormones in serum. Blood samples were collected and used for Hg measurement using
the ICP-MS method, and separated serum was used for hormone analysis. The study showed the
existence of a statistically significant difference in Hg levels measured in healthy and sick subjects
and the existence of a dose-response relationship between Hg and all measured hormones, with a
narrow interval obtained for the Hg-TSH pair. The results of this research support the use of the
Benchmark dose approach for the purpose of analyzing data from human studies, and our further
research will be focused on examining the impact of low doses on animal models in order to
determine more precise effects of low doses on the organism., Živa (Hg) je jedan od najznačajnijih zagađivača životne sredine sa osobinama endokrinog ometača. Malo je podataka iz epidemioloških studija koji opisuju odnos doza-odgovor između nivoa toksičnih metala i nivoa hormona. Cilj ovog rada bio je da primenom nearest neighbor matching analize utvrdi razliku u koncentraciji Hg kod zdravih/obolelih ispitanika od bolesti štitaste žlezde i da primenom Benchmark modelovanja utvrdi odnos doza-odgovor između nivoa Hg u krvi i tireostimulišućeg hormona (TSH) i tiroidnih hormona u serumu. Uzorci krvi su sakupljeni i korišćeni za merenje Hg uz pomoć ICP-MS metode, a izdvojeni serum korišćen je za analizu hormona. Studija je pokazala postojanje statistički značajne razlike u nivoima Hg koji su izmereni kod zdravih i bolesnih ispitanika i postojanje odnosa doza-odgovor između Hg i svih merenih hormona, pri čemu je uzak interval dobijen za Hg-TSH par. Rezultati ovog istraživanja podržavaju upotrebu Benchmark dose pristupa u svrhu analize podataka iz humanih studija, a naša dalja istraživanja će biti usmerena na ispitivanje uticaja niskih doza na životinjskim modelima, u cilju utvrđivanja preciznijih efekata niskih doza na organizam.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Exposure to mercury and thyroid function: Is there a connection?, Izloženost živi i funkcija štitaste žlezde: postoji li veza?",
volume = "72",
number = "5",
pages = "468-485",
doi = "10.5937/arhfarm72-40122"
}
Marić, Đ., Bonderović, V., Javorac, D., Baralić, K., Bulat, Z., Đukić-Ćosić, D., Mandić-Rajčević, S., Žarković, M.,& Buha-Đorđević, A.. (2022). Exposure to mercury and thyroid function: Is there a connection?. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 72(5), 468-485.
https://doi.org/10.5937/arhfarm72-40122
Marić Đ, Bonderović V, Javorac D, Baralić K, Bulat Z, Đukić-Ćosić D, Mandić-Rajčević S, Žarković M, Buha-Đorđević A. Exposure to mercury and thyroid function: Is there a connection?. in Arhiv za farmaciju. 2022;72(5):468-485.
doi:10.5937/arhfarm72-40122 .
Marić, Đurđica, Bonderović, Vera, Javorac, Dragana, Baralić, Katarina, Bulat, Zorica, Đukić-Ćosić, Danijela, Mandić-Rajčević, Stefan, Žarković, Miloš, Buha-Đorđević, Aleksandra, "Exposure to mercury and thyroid function: Is there a connection?" in Arhiv za farmaciju, 72, no. 5 (2022):468-485,
https://doi.org/10.5937/arhfarm72-40122 . .
3
2

Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor

Petrović, Bojana; Gladović, Ana; Javorac, Dragana; Buha-Đorđević, Aleksandra; Ćurčić, Marijana; Đukić-Ćosić, Danijela; Šoštarić, Andrej; Antonijević, Biljana; Bulat, Zorica

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Petrović, Bojana
AU  - Gladović, Ana
AU  - Javorac, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Šoštarić, Andrej
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4643
AB  - One of the most polluted cities in Serbia and Europe is Bor, due to mining and
smelting processes in Mining-Metallurgical Complex in Bor. Mining activities release mainly
SO2 and paritculate matter in air (1) and, as arsenic is usually found in copper and lead ores,
air quality monitoring in Bor has been showing its presence in exceeded annual limit
concentrations in past few years. Exposure to arsenic is related with anemia, skin changes,
peripheral neuropathy and cancer development. This study was carried out to assess
children’s and adult’s exposure to arsenic bound to PM10 and to charcterize risk from their
exposure through the air in the city of Bor. Mean yearly concentrations of arsenic were used
from Reports of the Serbian Enviromental Protection Agency, for measuring stations: Bor-
City park, Bor 1, Bor 2 and Bor-Jugopetrol. The USEPA method was used to assess non-
carcinogenic and carcinogenic risk, which classifies non-carcinogenic risk as acceptable (<1)
or unacceptable (>1) based on hazard quotient (HQ) values for three main exposure
pathways, while cancer risk classification is based on CR values also as acceptable (<1×10 -4 )
or unacceptable (>1×10 -4 ) (2). HQinh values exceeded safe level both for children and adults
on all measuring stations, describing risk as unacceptable via inhalation exposure.
Unacceptable carcinogenic risk for children was calculated on measuring station Bor-
Jugopetrol and for adults on measuring stations Bor-City park, Bor 1 and Bor-Jugopetrol.
Actions for reduction of arsenic release into the air should be taken due to obtained results
for city of Bor.
AB  - Grad Bor spada među najzagađenije gradove u Republici Srbiji i Evropi. Najveći izvor
zagađenja u ovom gradu predstavlja rudnik bakra, Rudarsko-topioničarski basen Bor, usled
emisije, predominantno, SO2 i suspendovanih čestica (1). Arsen je čest pratilac ruda bakra i
olova, te se iz godine u godinu monitoringom kvaliteta vazduha uočava njegovo prisustvo u
koncentracijama koje prelaze dozvoljene godišnje granice. Izloženost arsenu može dovesti
do razvoja anemije, promena na koži, periferne neuropatije, ali i razvoja karcinoma. Cilj rada
bio je da se proceni izloženost i okarakteriše rizik dece i odraslih od izloženosti arsenu iz
PM10 čestica tj. putem zagađenog vazduha u gradu Boru. Vrednosti prosečnih godišnjih
koncentracija arsena u vazduhu su preuzete iz godišnjih izveštaja Agencije za zaštitu životne
sredine, za merne stanice: Bor-Gradski park, Bor 1, Bor 2 i Bor-Jugopetrol. Zdravstveni rizik
je procenjen metodologijom koju preporučuje Američka agencija za zaštitu životne sredine.
Na osnovu vrednosti količnika hazarda (HQ) za oralni, inhalacioni i dermalni put unosa, ne-
karcinogeni rizik se klasifikuje kao prihvatljiv (<1) ili neprihvatljiv (>1), dok se karcinogeni
rizik klasifikuje na osnovu vrednosti CR, takođe kao prihvatljiv (<1×10-4 ) ili neprihvaljiv
(>1×10 -4 ) (2). Izračunate vrednosti HQinh za decu i odrasle prelaze vrednost 1 ukazujući na
neprihvatljiv rizik od izloženosti arsenu preko PM10 čestica iz zagađenog vazduha na svim
razmatranim mernim stanicama. Neprihvatljiv karcinogeni rizik za decu je izračunat na
stanici Bor-Jugopetrol, a za odrasle na stanicama Bor-Gradski park, Bor 1 i Bor-Jugopetrol.
Dobijeni rezultati ukazuju na preku potrebu preduzimanja mera u cilju smanjenja emisije
arsena u vazduh u Boru.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor
T1  - Procena rizika od izloženosti dece i odraslih arsenu u PM10 česticama putem zagađenog vazduha u Boru
VL  - 72
IS  - 4 suplement
SP  - S615
EP  - S616
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4643
ER  - 
@conference{
author = "Petrović, Bojana and Gladović, Ana and Javorac, Dragana and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Šoštarić, Andrej and Antonijević, Biljana and Bulat, Zorica",
year = "2022",
abstract = "One of the most polluted cities in Serbia and Europe is Bor, due to mining and
smelting processes in Mining-Metallurgical Complex in Bor. Mining activities release mainly
SO2 and paritculate matter in air (1) and, as arsenic is usually found in copper and lead ores,
air quality monitoring in Bor has been showing its presence in exceeded annual limit
concentrations in past few years. Exposure to arsenic is related with anemia, skin changes,
peripheral neuropathy and cancer development. This study was carried out to assess
children’s and adult’s exposure to arsenic bound to PM10 and to charcterize risk from their
exposure through the air in the city of Bor. Mean yearly concentrations of arsenic were used
from Reports of the Serbian Enviromental Protection Agency, for measuring stations: Bor-
City park, Bor 1, Bor 2 and Bor-Jugopetrol. The USEPA method was used to assess non-
carcinogenic and carcinogenic risk, which classifies non-carcinogenic risk as acceptable (<1)
or unacceptable (>1) based on hazard quotient (HQ) values for three main exposure
pathways, while cancer risk classification is based on CR values also as acceptable (<1×10 -4 )
or unacceptable (>1×10 -4 ) (2). HQinh values exceeded safe level both for children and adults
on all measuring stations, describing risk as unacceptable via inhalation exposure.
Unacceptable carcinogenic risk for children was calculated on measuring station Bor-
Jugopetrol and for adults on measuring stations Bor-City park, Bor 1 and Bor-Jugopetrol.
Actions for reduction of arsenic release into the air should be taken due to obtained results
for city of Bor., Grad Bor spada među najzagađenije gradove u Republici Srbiji i Evropi. Najveći izvor
zagađenja u ovom gradu predstavlja rudnik bakra, Rudarsko-topioničarski basen Bor, usled
emisije, predominantno, SO2 i suspendovanih čestica (1). Arsen je čest pratilac ruda bakra i
olova, te se iz godine u godinu monitoringom kvaliteta vazduha uočava njegovo prisustvo u
koncentracijama koje prelaze dozvoljene godišnje granice. Izloženost arsenu može dovesti
do razvoja anemije, promena na koži, periferne neuropatije, ali i razvoja karcinoma. Cilj rada
bio je da se proceni izloženost i okarakteriše rizik dece i odraslih od izloženosti arsenu iz
PM10 čestica tj. putem zagađenog vazduha u gradu Boru. Vrednosti prosečnih godišnjih
koncentracija arsena u vazduhu su preuzete iz godišnjih izveštaja Agencije za zaštitu životne
sredine, za merne stanice: Bor-Gradski park, Bor 1, Bor 2 i Bor-Jugopetrol. Zdravstveni rizik
je procenjen metodologijom koju preporučuje Američka agencija za zaštitu životne sredine.
Na osnovu vrednosti količnika hazarda (HQ) za oralni, inhalacioni i dermalni put unosa, ne-
karcinogeni rizik se klasifikuje kao prihvatljiv (<1) ili neprihvatljiv (>1), dok se karcinogeni
rizik klasifikuje na osnovu vrednosti CR, takođe kao prihvatljiv (<1×10-4 ) ili neprihvaljiv
(>1×10 -4 ) (2). Izračunate vrednosti HQinh za decu i odrasle prelaze vrednost 1 ukazujući na
neprihvatljiv rizik od izloženosti arsenu preko PM10 čestica iz zagađenog vazduha na svim
razmatranim mernim stanicama. Neprihvatljiv karcinogeni rizik za decu je izračunat na
stanici Bor-Jugopetrol, a za odrasle na stanicama Bor-Gradski park, Bor 1 i Bor-Jugopetrol.
Dobijeni rezultati ukazuju na preku potrebu preduzimanja mera u cilju smanjenja emisije
arsena u vazduh u Boru.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor, Procena rizika od izloženosti dece i odraslih arsenu u PM10 česticama putem zagađenog vazduha u Boru",
volume = "72",
number = "4 suplement",
pages = "S615-S616",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4643"
}
Petrović, B., Gladović, A., Javorac, D., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D., Šoštarić, A., Antonijević, B.,& Bulat, Z.. (2022). Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S615-S616.
https://hdl.handle.net/21.15107/rcub_farfar_4643
Petrović B, Gladović A, Javorac D, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Šoštarić A, Antonijević B, Bulat Z. Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor. in Arhiv za farmaciju. 2022;72(4 suplement):S615-S616.
https://hdl.handle.net/21.15107/rcub_farfar_4643 .
Petrović, Bojana, Gladović, Ana, Javorac, Dragana, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Šoštarić, Andrej, Antonijević, Biljana, Bulat, Zorica, "Health risk assessment of children’s and adult’s exposure to arsenic bound to PM10 in the city of Bor" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S615-S616,
https://hdl.handle.net/21.15107/rcub_farfar_4643 .