TY  - JOUR
AU  - Vukelić, Dragana
AU  - Baralić, Katarina
AU  - Marić, Đurđica
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Panieri, Emiliano
AU  - Saso, Luciano
AU  - Buha-Đorđević, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5313
AB  - The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances.
PB  - Elsevier B.V.
T2  - Science of the Total Environment
T1  - Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status
VL  - 908
DO  - 10.1016/j.scitotenv.2023.168352
ER  - 

@article{
author = "Vukelić, Dragana and Baralić, Katarina and Marić, Đurđica and Đukić-Ćosić, Danijela and Bulat, Zorica and Panieri, Emiliano and Saso, Luciano and Buha-Đorđević, Aleksandra",
year = "2024",
abstract = "The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances.",
publisher = "Elsevier B.V.",
journal = "Science of the Total Environment",
title = "Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status",
volume = "908",
doi = "10.1016/j.scitotenv.2023.168352"
}

Vukelić, D., Baralić, K., Marić, Đ., Đukić-Ćosić, D., Bulat, Z., Panieri, E., Saso, L.,& Buha-Đorđević, A.. (2024). Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status. in Science of the Total Environment
Elsevier B.V.., 908.
https://doi.org/10.1016/j.scitotenv.2023.168352

Vukelić D, Baralić K, Marić Đ, Đukić-Ćosić D, Bulat Z, Panieri E, Saso L, Buha-Đorđević A. Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status. in Science of the Total Environment. 2024;908.
doi:10.1016/j.scitotenv.2023.168352 .

Vukelić, Dragana, Baralić, Katarina, Marić, Đurđica, Đukić-Ćosić, Danijela, Bulat, Zorica, Panieri, Emiliano, Saso, Luciano, Buha-Đorđević, Aleksandra, "Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status" in Science of the Total Environment, 908 (2024),
https://doi.org/10.1016/j.scitotenv.2023.168352 . .

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 . .

TY  - CONF
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5419
AB  - Ekspozom predstavlja sredinski ekvivalent ljudskom genomu. Istražujući ulogu toksičnih metala u različitim endokrinim poremećajima, projekat DecodExpo je nastojao da istraži kompleksne uticaje poreklom iz životne sredine na ljudsko endokrino zdravlje. Prvi deo projekta sastojao se iz studije hu- manog biomonitoringa (HBM), koja je nastojala da utvrdi nivoe odabranih šest toksičnih meta(oid)a (Pb, Cd, Hg, As, Cr i Ni), kojima su ljudi izloženi u svakodnevnom životu, kao i da ispita vezu između metala i različitih nivoa hormona u organizmu. ...
AB  - The exposome represents the environmental equivalent of the human genome. The DecodExpo project
aimed to explore the relationship between toxic metals present in the environment and various
endocrine disorders. The first part of the project involved a human biomonitoring (HBM) study, which
measured the levels of six toxic metal(oid)s (Pb, Cd, Hg, As, Cr, and Ni) in the general population and
examined their connection to hormone levels in the body.  ...
PB  - Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
T1  - Ispitivanje uloge ekspozoma u endokrinom zdravlju ljudi: rezultati DecodExpo projekta
T1  - Investing the role of exposome in human endocrine health: DecodExpo project results
SP  - 11
EP  - 12
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5419
ER  - 

@conference{
author = "Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Ekspozom predstavlja sredinski ekvivalent ljudskom genomu. Istražujući ulogu toksičnih metala u različitim endokrinim poremećajima, projekat DecodExpo je nastojao da istraži kompleksne uticaje poreklom iz životne sredine na ljudsko endokrino zdravlje. Prvi deo projekta sastojao se iz studije hu- manog biomonitoringa (HBM), koja je nastojala da utvrdi nivoe odabranih šest toksičnih meta(oid)a (Pb, Cd, Hg, As, Cr i Ni), kojima su ljudi izloženi u svakodnevnom životu, kao i da ispita vezu između metala i različitih nivoa hormona u organizmu. ..., The exposome represents the environmental equivalent of the human genome. The DecodExpo project
aimed to explore the relationship between toxic metals present in the environment and various
endocrine disorders. The first part of the project involved a human biomonitoring (HBM) study, which
measured the levels of six toxic metal(oid)s (Pb, Cd, Hg, As, Cr, and Ni) in the general population and
examined their connection to hormone levels in the body.  ...",
publisher = "Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book",
title = "Ispitivanje uloge ekspozoma u endokrinom zdravlju ljudi: rezultati DecodExpo projekta, Investing the role of exposome in human endocrine health: DecodExpo project results",
pages = "11-12",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5419"
}

Buha-Đorđević, A.. (2023). Ispitivanje uloge ekspozoma u endokrinom zdravlju ljudi: rezultati DecodExpo projekta. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
Udruženje toksikologa Srbije., 11-12.
https://hdl.handle.net/21.15107/rcub_farfar_5419

Buha-Đorđević A. Ispitivanje uloge ekspozoma u endokrinom zdravlju ljudi: rezultati DecodExpo projekta. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book. 2023;:11-12.
https://hdl.handle.net/21.15107/rcub_farfar_5419 .

Buha-Đorđević, Aleksandra, "Ispitivanje uloge ekspozoma u endokrinom zdravlju ljudi: rezultati DecodExpo projekta" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book (2023):11-12,
https://hdl.handle.net/21.15107/rcub_farfar_5419 .

TY  - CONF
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Mandić-Rajčević, Stefan
AU  - Žarković, Miloš
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5426
AB  - Uticaj toksičnog metala nikla (Ni) na funkciju štitaste žlezde još uvek nije dovoljno istražen.
Stoga je cilj ove studije bio da se ispita potencijal Ni da poremeti funkciju štitaste žlezde ispitivanjem
odnosa između koncentracije Ni u krvi i nivoa hormona u serumu (TSH, T4, T3, fT4, fT3), kao i parametara
tiroidne homeostaze (SPINA-GT i SPINA-GD) korišćenjem korelacione analize i Benchmark (BMD) koncepta. ...
AB  - Nickel (Ni) is one of the well-known toxic metals whose effect on thyroid function has not been suffi-
ciently investigated yet. The aim of this study was to analyse the potential of Ni to disrupt thyroid func-
tion by exploring the relationship between blood Ni concentration and serum hormone levels (TSH,
T4, T3, fT4, fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using
correlation analysis and Benchmark (BMD) concept ...
PB  - Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
T1  - Veza između izloženosti niklu i poremećaja funkcije štitaste žlezde - rezultati studije humanog biomonitoringa
T1  - The relationship between nickel exposure and thyroid dysfunction - results of a human biomonitoring study
SP  - 63
EP  - 64
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5426
ER  - 

@conference{
author = "Marić, Đurđica and Baralić, Katarina and Vukelić, Dragana and Mandić-Rajčević, Stefan and Žarković, Miloš and Antonijević, Biljana and Đukić-Ćosić, Danijela and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Uticaj toksičnog metala nikla (Ni) na funkciju štitaste žlezde još uvek nije dovoljno istražen.
Stoga je cilj ove studije bio da se ispita potencijal Ni da poremeti funkciju štitaste žlezde ispitivanjem
odnosa između koncentracije Ni u krvi i nivoa hormona u serumu (TSH, T4, T3, fT4, fT3), kao i parametara
tiroidne homeostaze (SPINA-GT i SPINA-GD) korišćenjem korelacione analize i Benchmark (BMD) koncepta. ..., Nickel (Ni) is one of the well-known toxic metals whose effect on thyroid function has not been suffi-
ciently investigated yet. The aim of this study was to analyse the potential of Ni to disrupt thyroid func-
tion by exploring the relationship between blood Ni concentration and serum hormone levels (TSH,
T4, T3, fT4, fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using
correlation analysis and Benchmark (BMD) concept ...",
publisher = "Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book",
title = "Veza između izloženosti niklu i poremećaja funkcije štitaste žlezde - rezultati studije humanog biomonitoringa, The relationship between nickel exposure and thyroid dysfunction - results of a human biomonitoring study",
pages = "63-64",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5426"
}

Marić, Đ., Baralić, K., Vukelić, D., Mandić-Rajčević, S., Žarković, M., Antonijević, B., Đukić-Ćosić, D., Bulat, Z.,& Buha-Đorđević, A.. (2023). Veza između izloženosti niklu i poremećaja funkcije štitaste žlezde - rezultati studije humanog biomonitoringa. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
Udruženje toksikologa Srbije., 63-64.
https://hdl.handle.net/21.15107/rcub_farfar_5426

Marić Đ, Baralić K, Vukelić D, Mandić-Rajčević S, Žarković M, Antonijević B, Đukić-Ćosić D, Bulat Z, Buha-Đorđević A. Veza između izloženosti niklu i poremećaja funkcije štitaste žlezde - rezultati studije humanog biomonitoringa. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book. 2023;:63-64.
https://hdl.handle.net/21.15107/rcub_farfar_5426 .

Marić, Đurđica, Baralić, Katarina, Vukelić, Dragana, Mandić-Rajčević, Stefan, Žarković, Miloš, Antonijević, Biljana, Đukić-Ćosić, Danijela, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Veza između izloženosti niklu i poremećaja funkcije štitaste žlezde - rezultati studije humanog biomonitoringa" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book (2023):63-64,
https://hdl.handle.net/21.15107/rcub_farfar_5426 .

TY  - JOUR
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Mandić-Rajčević, Stefan
AU  - Žarković, Miloš
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5144
AB  - Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept. Methods: Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results. Results and discussion: The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances. Copyright
PB  - Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Nickel as a potential disruptor of thyroid function: benchmark modelling of human data
VL  - 14
DO  - 10.3389/fendo.2023.1145153
ER  - 

@article{
author = "Marić, Đurđica and Baralić, Katarina and Javorac, Dragana and Mandić-Rajčević, Stefan and Žarković, Miloš and Antonijević, Biljana and Đukić-Ćosić, Danijela and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept. Methods: Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results. Results and discussion: The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances. Copyright",
publisher = "Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Nickel as a potential disruptor of thyroid function: benchmark modelling of human data",
volume = "14",
doi = "10.3389/fendo.2023.1145153"
}

Marić, Đ., Baralić, K., Javorac, D., Mandić-Rajčević, S., Žarković, M., Antonijević, B., Đukić-Ćosić, D., Bulat, Z.,& Buha-Đorđević, A.. (2023). Nickel as a potential disruptor of thyroid function: benchmark modelling of human data. in Frontiers in Endocrinology
Frontiers Media SA., 14.
https://doi.org/10.3389/fendo.2023.1145153

Marić Đ, Baralić K, Javorac D, Mandić-Rajčević S, Žarković M, Antonijević B, Đukić-Ćosić D, Bulat Z, Buha-Đorđević A. Nickel as a potential disruptor of thyroid function: benchmark modelling of human data. in Frontiers in Endocrinology. 2023;14.
doi:10.3389/fendo.2023.1145153 .

Marić, Đurđica, Baralić, Katarina, Javorac, Dragana, Mandić-Rajčević, Stefan, Žarković, Miloš, Antonijević, Biljana, Đukić-Ćosić, Danijela, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Nickel as a potential disruptor of thyroid function: benchmark modelling of human data" in Frontiers in Endocrinology, 14 (2023),
https://doi.org/10.3389/fendo.2023.1145153 . .

TY  - CONF
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Marić, Đurđica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5174
AB  - Toxic metal(oid)s are being frequently referred to as endocrine-disrupting chemicals (EDCs), and as they are prevalent in nature, they may be linked to the current reproductive issues confronting the female population. [1,2]  ...
PB  - Elsevier
C3  - Toxicology Letters
T1  - Metals in the Mix: Uncovering the Link Between Real-Life Environmental Exposures, Hormone Disruption, and Female Reproductive Health using Human and Animal Data
VL  - 384
IS  - S1
SP  - S145
EP  - S145
DO  - 10.1016/S0378-4274(23)00609-4
ER  - 

@conference{
author = "Baralić, Katarina and Vukelić, Dragana and Marić, Đurđica and Antonijević, Biljana and Đukić-Ćosić, Danijela and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Toxic metal(oid)s are being frequently referred to as endocrine-disrupting chemicals (EDCs), and as they are prevalent in nature, they may be linked to the current reproductive issues confronting the female population. [1,2]  ...",
publisher = "Elsevier",
journal = "Toxicology Letters",
title = "Metals in the Mix: Uncovering the Link Between Real-Life Environmental Exposures, Hormone Disruption, and Female Reproductive Health using Human and Animal Data",
volume = "384",
number = "S1",
pages = "S145-S145",
doi = "10.1016/S0378-4274(23)00609-4"
}

Baralić, K., Vukelić, D., Marić, Đ., Antonijević, B., Đukić-Ćosić, D., Bulat, Z.,& Buha-Đorđević, A.. (2023). Metals in the Mix: Uncovering the Link Between Real-Life Environmental Exposures, Hormone Disruption, and Female Reproductive Health using Human and Animal Data. in Toxicology Letters
Elsevier., 384(S1), S145-S145.
https://doi.org/10.1016/S0378-4274(23)00609-4

Baralić K, Vukelić D, Marić Đ, Antonijević B, Đukić-Ćosić D, Bulat Z, Buha-Đorđević A. Metals in the Mix: Uncovering the Link Between Real-Life Environmental Exposures, Hormone Disruption, and Female Reproductive Health using Human and Animal Data. in Toxicology Letters. 2023;384(S1):S145-S145.
doi:10.1016/S0378-4274(23)00609-4 .

Baralić, Katarina, Vukelić, Dragana, Marić, Đurđica, Antonijević, Biljana, Đukić-Ćosić, Danijela, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Metals in the Mix: Uncovering the Link Between Real-Life Environmental Exposures, Hormone Disruption, and Female Reproductive Health using Human and Animal Data" in Toxicology Letters, 384, no. S1 (2023):S145-S145,
https://doi.org/10.1016/S0378-4274(23)00609-4 . .

TY  - CONF
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5173
AB  - Infertility and other reproductive health issues have emerged as one of the world’s foremost challenges in recent decades. Globally, around 15% of couples suffer from infertility, and male partners are shown to be responsible for about 20–30% of infertility cases. ...
PB  - Elsevier
C3  - Toxicology Letters
T1  - The effect of real-life toxic metal(oid)s mixture on the redox status in testicular tissues of rats
VL  - 384
IS  - S1
SP  - S144
EP  - S144
DO  - 10.1016/S0378-4274(23)00607-0
ER  - 

@conference{
author = "Marić, Đurđica and Baralić, Katarina and Vukelić, Dragana and Đukić-Ćosić, Danijela and Bulat, Zorica and Antonijević, Biljana and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Infertility and other reproductive health issues have emerged as one of the world’s foremost challenges in recent decades. Globally, around 15% of couples suffer from infertility, and male partners are shown to be responsible for about 20–30% of infertility cases. ...",
publisher = "Elsevier",
journal = "Toxicology Letters",
title = "The effect of real-life toxic metal(oid)s mixture on the redox status in testicular tissues of rats",
volume = "384",
number = "S1",
pages = "S144-S144",
doi = "10.1016/S0378-4274(23)00607-0"
}

Marić, Đ., Baralić, K., Vukelić, D., Đukić-Ćosić, D., Bulat, Z., Antonijević, B.,& Buha-Đorđević, A.. (2023). The effect of real-life toxic metal(oid)s mixture on the redox status in testicular tissues of rats. in Toxicology Letters
Elsevier., 384(S1), S144-S144.
https://doi.org/10.1016/S0378-4274(23)00607-0

Marić Đ, Baralić K, Vukelić D, Đukić-Ćosić D, Bulat Z, Antonijević B, Buha-Đorđević A. The effect of real-life toxic metal(oid)s mixture on the redox status in testicular tissues of rats. in Toxicology Letters. 2023;384(S1):S144-S144.
doi:10.1016/S0378-4274(23)00607-0 .

Marić, Đurđica, Baralić, Katarina, Vukelić, Dragana, Đukić-Ćosić, Danijela, Bulat, Zorica, Antonijević, Biljana, Buha-Đorđević, Aleksandra, "The effect of real-life toxic metal(oid)s mixture on the redox status in testicular tissues of rats" in Toxicology Letters, 384, no. S1 (2023):S144-S144,
https://doi.org/10.1016/S0378-4274(23)00607-0 . .

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 . .

TY  - JOUR
AU  - Đukić-Ćosić, Danijela
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Bulat, Zorica
AU  - Ćurčić, Marijana
AU  - Antonijević, Biljana
AU  - Đorđević, Vladimir
AU  - Repić, Aleksandra
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4277
AB  - The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) μg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.
PB  - Elsevier Inc
T2  - Environmental Research
T1  - Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor
VL  - 215
DO  - 10.1016/j.envres.2022.114283
ER  - 

@article{
author = "Đukić-Ćosić, Danijela and Baralić, Katarina and Javorac, Dragana and Bulat, Zorica and Ćurčić, Marijana and Antonijević, Biljana and Đorđević, Vladimir and Repić, Aleksandra and Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) μg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.",
publisher = "Elsevier Inc",
journal = "Environmental Research",
title = "Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor",
volume = "215",
doi = "10.1016/j.envres.2022.114283"
}

Đukić-Ćosić, D., Baralić, K., Javorac, D., Bulat, Z., Ćurčić, M., Antonijević, B., Đorđević, V., Repić, A.,& Buha-Đorđević, A.. (2022). Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor. in Environmental Research
Elsevier Inc., 215.
https://doi.org/10.1016/j.envres.2022.114283

Đukić-Ćosić D, Baralić K, Javorac D, Bulat Z, Ćurčić M, Antonijević B, Đorđević V, Repić A, Buha-Đorđević A. Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor. in Environmental Research. 2022;215.
doi:10.1016/j.envres.2022.114283 .

Đukić-Ćosić, Danijela, Baralić, Katarina, Javorac, Dragana, Bulat, Zorica, Ćurčić, Marijana, Antonijević, Biljana, Đorđević, Vladimir, Repić, Aleksandra, Buha-Đorđević, Aleksandra, "Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor" in Environmental Research, 215 (2022),
https://doi.org/10.1016/j.envres.2022.114283 . .

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 .

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 . .

TY  - CONF
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Mandić-Rajčević, Stefan
AU  - Đorđević, Vladimir
AU  - Đukić-Ćosić, Danijela
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4353
PB  - Elsevier B.V.
C3  - Toxicology Letters
T1  - Arsenic - effect on insulin level in the general population of Serbia
VL  - 368
IS  - Supplement
SP  - S276
EP  - S276
DO  - 10.1016/j.toxlet.2022.07.730
ER  - 

@conference{
author = "Marić, Đurđica and Baralić, Katarina and Javorac, Dragana and Mandić-Rajčević, Stefan and Đorđević, Vladimir and Đukić-Ćosić, Danijela and Ćurčić, Marijana and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2022",
publisher = "Elsevier B.V.",
journal = "Toxicology Letters",
title = "Arsenic - effect on insulin level in the general population of Serbia",
volume = "368",
number = "Supplement",
pages = "S276-S276",
doi = "10.1016/j.toxlet.2022.07.730"
}

Marić, Đ., Baralić, K., Javorac, D., Mandić-Rajčević, S., Đorđević, V., Đukić-Ćosić, D., Ćurčić, M., Bulat, Z.,& Buha-Đorđević, A.. (2022). Arsenic - effect on insulin level in the general population of Serbia. in Toxicology Letters
Elsevier B.V.., 368(Supplement), S276-S276.
https://doi.org/10.1016/j.toxlet.2022.07.730

Marić Đ, Baralić K, Javorac D, Mandić-Rajčević S, Đorđević V, Đukić-Ćosić D, Ćurčić M, Bulat Z, Buha-Đorđević A. Arsenic - effect on insulin level in the general population of Serbia. in Toxicology Letters. 2022;368(Supplement):S276-S276.
doi:10.1016/j.toxlet.2022.07.730 .

Marić, Đurđica, Baralić, Katarina, Javorac, Dragana, Mandić-Rajčević, Stefan, Đorđević, Vladimir, Đukić-Ćosić, Danijela, Ćurčić, Marijana, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Arsenic - effect on insulin level in the general population of Serbia" in Toxicology Letters, 368, no. Supplement (2022):S276-S276,
https://doi.org/10.1016/j.toxlet.2022.07.730 . .

TY  - CONF
AU  - Baralić, Katarina
AU  - Javorac, Dragana
AU  - Marić, Đurđica
AU  - Antonijević-Mljaković, Evica
AU  - Đukić-Ćosić, Danijela
AU  - Zarković, Miloš
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4347
PB  - Elsevier B.V.
C3  - Toxicology Letters
T1  - Mercury-induced changes in serum insulin level: Benchmark modeling approach
VL  - 368
IS  - Supplement
SP  - S276
EP  - S276
DO  - 10.1016/j.toxlet.2022.07.729
ER  - 

@conference{
author = "Baralić, Katarina and Javorac, Dragana and Marić, Đurđica and Antonijević-Mljaković, Evica and Đukić-Ćosić, Danijela and Zarković, Miloš and Antonijević, Biljana and Bulat, Zorica and Buha-Đorđević, Aleksandra",
year = "2022",
publisher = "Elsevier B.V.",
journal = "Toxicology Letters",
title = "Mercury-induced changes in serum insulin level: Benchmark modeling approach",
volume = "368",
number = "Supplement",
pages = "S276-S276",
doi = "10.1016/j.toxlet.2022.07.729"
}

Baralić, K., Javorac, D., Marić, Đ., Antonijević-Mljaković, E., Đukić-Ćosić, D., Zarković, M., Antonijević, B., Bulat, Z.,& Buha-Đorđević, A.. (2022). Mercury-induced changes in serum insulin level: Benchmark modeling approach. in Toxicology Letters
Elsevier B.V.., 368(Supplement), S276-S276.
https://doi.org/10.1016/j.toxlet.2022.07.729

Baralić K, Javorac D, Marić Đ, Antonijević-Mljaković E, Đukić-Ćosić D, Zarković M, Antonijević B, Bulat Z, Buha-Đorđević A. Mercury-induced changes in serum insulin level: Benchmark modeling approach. in Toxicology Letters. 2022;368(Supplement):S276-S276.
doi:10.1016/j.toxlet.2022.07.729 .

Baralić, Katarina, Javorac, Dragana, Marić, Đurđica, Antonijević-Mljaković, Evica, Đukić-Ćosić, Danijela, Zarković, Miloš, Antonijević, Biljana, Bulat, Zorica, Buha-Đorđević, Aleksandra, "Mercury-induced changes in serum insulin level: Benchmark modeling approach" in Toxicology Letters, 368, no. Supplement (2022):S276-S276,
https://doi.org/10.1016/j.toxlet.2022.07.729 . .

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 . .

TY  - CONF
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4488
AB  - The term exposome describes every exposure from the environment to which an
individual is subjected from conception to death. Rapidly increasing evidence has
documented that exposure to endocrine-disrupting chemicals (EDCs), an important part of
the exposome, substantially contributes to disease and dysfunction across the life span. To
date, however, there have been few studies investigating simultaneous exposure to multiple
EDCs in mixtures, although this scenario entails real-life exposures. This paper will present
the “Decoding the role of exposome in endocrine health” – DecodExpo project funded by the
Science Fund of the Republic of Serbia. The project aims to provide scientific evidence for the
role of toxic metal(oid)s mixtures (As, Pb, Hg, Cd, Cr, and Ni) in the development of various
endocrine disorders. The project consists of human biomonitoring (HBM), exposome-wide
association, and animal studies. Namely, data on blood levels of toxic metal(oid)s in different
cohort groups within the Serbian general population were collected (435 participants) and,
by performing mathematical modelling, dose-response relationships were determined
between certain toxic metals and hormone blood levels. The study protocol for the animal
study was chosen based on the results of the HBM study, to address the main challenges in
studies on EDCs (non-monotonic dose-response, long-term exposure to low doses, exposure
to mixtures of EDCs, sex differences). Furthermore, various endpoints are tested to ensure
better insight into molecular, biochemical, and structural changes in the endocrine system.
The project revealed an important role of exposure to the investigated toxic metal(oid)s
mixture in human endocrine health.
AB  - Izraz ekspozom opisuje sve uticaje iz životne sredine kojima je pojedinac izložen od
začeć a do smrti. Brojni naučni dokazi ukazuju da izloženost hemikalijama koje ometaju rad
endokrinog sistema, endokrinim ometačima, važnim komponentama ekspozoma, značajno
doprinosi nastanku bolesti i različitim poremećajima tokom životnog veka. Međutim, malo je
studija koje istražuju istovremenu izloženost endokrinim ometačima koji su u prirodi
prisutni u smešama, iako baš ovaj scenario odslikava izloženost u stvarnom životu. Ovo
predavanje daje kratak prikaz projekta „Dekodiranje uloge ekspozoma u endokrinom
zdravlju” – DecodExpo koji finansira Fond za nauku Republike Srbije u okviru PROMIS
programa. Projekat ima za cilj da pruži naučne dokaze o ulozi smeše toksičnih metal(oid)a
(As, Pb, Hg, Cd, Cr, i Ni) u razvoju različitih endokrinih poremeć aja i bolesti. Ovo istraživanje
obuhvatilo je studije humanog biomonitoringa (HBM), ispitivanje veze ekspozoma i zdravlje,
te studije na životinjama. Naime, prikupljeni su podaci o nivoima toksičnih metala u krvi kod
ispitanika iz opšte populacije Srbije (435 učesnika) i matematičkim modeliranjem utvrđeni
su odnosi doza-odgovor između nivoa pojedinih metal(oida)a i nivoa hormona u krvi.
Protokol studije na životinjama izabran je na osnovu rezultata HBM studije, kako bi se
odgovorilo na glavne izazove sa kojima se naučnici suočavaju pri sprovođenju studija o
endokrinim ometačima (nemonotoni odnos doza-odgovor, dugotrajno izlaganje niskim
dozama, izloženost smešama, razlike među polovima). Pored toga, ispitani su različiti
parametri kako bi se obezbedio bolji uvid u molekularne, biohemijske i strukturne promene
u endokrinom sistemu. Projekat otkriva važnu ulogu koju izloženost ovoj toksičnoj smeši
metal(oid)a ima u ljudskom endokrinom zdravlju.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Exposome and endocrine health
T1  - Ekspozom i endokrino zdravlje ljudi
VL  - 72
IS  - 4 suplement
SP  - S176
EP  - S177
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4488
ER  - 

@conference{
author = "Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "The term exposome describes every exposure from the environment to which an
individual is subjected from conception to death. Rapidly increasing evidence has
documented that exposure to endocrine-disrupting chemicals (EDCs), an important part of
the exposome, substantially contributes to disease and dysfunction across the life span. To
date, however, there have been few studies investigating simultaneous exposure to multiple
EDCs in mixtures, although this scenario entails real-life exposures. This paper will present
the “Decoding the role of exposome in endocrine health” – DecodExpo project funded by the
Science Fund of the Republic of Serbia. The project aims to provide scientific evidence for the
role of toxic metal(oid)s mixtures (As, Pb, Hg, Cd, Cr, and Ni) in the development of various
endocrine disorders. The project consists of human biomonitoring (HBM), exposome-wide
association, and animal studies. Namely, data on blood levels of toxic metal(oid)s in different
cohort groups within the Serbian general population were collected (435 participants) and,
by performing mathematical modelling, dose-response relationships were determined
between certain toxic metals and hormone blood levels. The study protocol for the animal
study was chosen based on the results of the HBM study, to address the main challenges in
studies on EDCs (non-monotonic dose-response, long-term exposure to low doses, exposure
to mixtures of EDCs, sex differences). Furthermore, various endpoints are tested to ensure
better insight into molecular, biochemical, and structural changes in the endocrine system.
The project revealed an important role of exposure to the investigated toxic metal(oid)s
mixture in human endocrine health., Izraz ekspozom opisuje sve uticaje iz životne sredine kojima je pojedinac izložen od
začeć a do smrti. Brojni naučni dokazi ukazuju da izloženost hemikalijama koje ometaju rad
endokrinog sistema, endokrinim ometačima, važnim komponentama ekspozoma, značajno
doprinosi nastanku bolesti i različitim poremećajima tokom životnog veka. Međutim, malo je
studija koje istražuju istovremenu izloženost endokrinim ometačima koji su u prirodi
prisutni u smešama, iako baš ovaj scenario odslikava izloženost u stvarnom životu. Ovo
predavanje daje kratak prikaz projekta „Dekodiranje uloge ekspozoma u endokrinom
zdravlju” – DecodExpo koji finansira Fond za nauku Republike Srbije u okviru PROMIS
programa. Projekat ima za cilj da pruži naučne dokaze o ulozi smeše toksičnih metal(oid)a
(As, Pb, Hg, Cd, Cr, i Ni) u razvoju različitih endokrinih poremeć aja i bolesti. Ovo istraživanje
obuhvatilo je studije humanog biomonitoringa (HBM), ispitivanje veze ekspozoma i zdravlje,
te studije na životinjama. Naime, prikupljeni su podaci o nivoima toksičnih metala u krvi kod
ispitanika iz opšte populacije Srbije (435 učesnika) i matematičkim modeliranjem utvrđeni
su odnosi doza-odgovor između nivoa pojedinih metal(oida)a i nivoa hormona u krvi.
Protokol studije na životinjama izabran je na osnovu rezultata HBM studije, kako bi se
odgovorilo na glavne izazove sa kojima se naučnici suočavaju pri sprovođenju studija o
endokrinim ometačima (nemonotoni odnos doza-odgovor, dugotrajno izlaganje niskim
dozama, izloženost smešama, razlike među polovima). Pored toga, ispitani su različiti
parametri kako bi se obezbedio bolji uvid u molekularne, biohemijske i strukturne promene
u endokrinom sistemu. Projekat otkriva važnu ulogu koju izloženost ovoj toksičnoj smeši
metal(oid)a ima u ljudskom endokrinom zdravlju.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Exposome and endocrine health, Ekspozom i endokrino zdravlje ljudi",
volume = "72",
number = "4 suplement",
pages = "S176-S177",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4488"
}

Buha-Đorđević, A.. (2022). Exposome and endocrine health. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S176-S177.
https://hdl.handle.net/21.15107/rcub_farfar_4488

Buha-Đorđević A. Exposome and endocrine health. in Arhiv za farmaciju. 2022;72(4 suplement):S176-S177.
https://hdl.handle.net/21.15107/rcub_farfar_4488 .

Buha-Đorđević, Aleksandra, "Exposome and endocrine health" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S176-S177,
https://hdl.handle.net/21.15107/rcub_farfar_4488 .

TY  - CONF
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4459
AB  - The human population is exposed to a vast number of chemicals that are known or
suspected endocrine disruptors. Although thresholds are mainly determined concerning a
single compound, in real life we are indeed exposed to multiple chemicals in mixtures, i.e.
toxic cocktails. The focus of this research was to determine the effects that toxic cocktails of
metal(oid)s have on human endocrine health The study involved 435 participants from the
general population of Serbia (218 women and 217 men) from five different cohorts (prostate
and testes cancer patients, breast cancer and benign breast dysplasia, pancreatic cancer,
thyroid, and metabolic disorders patients, and healthy volunteers). Blood cadmium (Cd),
lead (Pb), arsenic (As), mercury (Hg), nickel (Ni), and chromium (Cr) levels and serum levels
of various hormones were measured in all collected samples. The statistical analyses were
performed using the R language while dose-response analysis was performed in PROAST
software. Levels estimated to produce the 10% extra risk of testosterone serum levels
disturbances were lower than median Hg levels measured in the general population. The
obtained results also provided support for the positive association between Pb exposure and
higher insulin levels. Similarly, the calculated levels that can produce 10% of extra risk for
the disturbances in free thyroxine levels were lower than the medium determined As levels.
These findings provide strong support for the endocrine-disrupting effects of the
investigated toxic cocktail of metal(oid)s present in our environment and suggest that
threshold values for such effects might be lower than those currently implemented.
AB  - Opšta populacija je svakodnevno izložena velikom broju hemikalija za koje se zna ili se
sumnja da su endokrini ometači. Iako se referentne doze uglavnom određuju za pojedinačne
hemikalije, u stvarnom životu smo zapravo izloženi hemikalijama u smešama, odnosno
toksičnim koktelima. Fokus istraživanja bio je na utvrđivanju uticaja koje toksični koktel
metala(oida) imaju na endokrino zdravlje ljudi. Istraživanje je obuhvatilo 435 učesnika iz
opšte populacije Republike Srbije (218 žena i 217 muškaraca) iz pet različitih kohorti
(pacijenti sa: karcinomima prostate ili testisa, karcinomom dojke ili benignom displazijom
dojke, karcinomom pankreasa, poremećajima štitaste žlezde i metaboličkim poremeć ajima,
te zdravi dobrovoljci). U prikupljenim uzorcima mereni su nivoi kadmijuma (Cd), olova (Pb),
arsena (As), žive (Hg), nikla (Ni) i hroma (Cr) u krvi, kao i nivoi različitih hormona u serumu.
Statističke analize su obavljene korišćenjem R statističkog paketa, dok je doza-odgovor
analiza vršena u PROAST softveru (RIVM, Holandija). Nivoi za koje se procenjuje da dovode
do dodatnog rizika od 10% za nastanak poremeć aja nivoa testosterona u serumu bili su niži
od medijane izmerenih nivoa Hg kod ispitanika. Dobijeni rezultati su takođe pružili podršku
postojanju veze između nivoa izloženosti Pb i viših nivoa insulina. Slično, izračunati nivoi As
u krvi koji mogu da izazovu 10% dodatnog rizika za poremeć aje nivoa slobodnog tiroksina
bili su niži od izračunate medijane za nivoe ovog metaloida u krvi. Ovi nalazi pružaju dokaze
o endokrinim efektima ispitivanog koktela toksičnih metal(oid)a i sugerišu da bi granične
vrednosti za takve efekte mogle biti niže od onih koje se trenutno primenjuju.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Decoding the role of toxic coctails of metals in endocrine health: the study in the general population of the Republic of Serbia
T1  - Dekodiranje uloge koktela toksičnih metala u endokrinom zdravlju: studija na opštoj populaciji Republike Srbije
VL  - 72
IS  - 4 suplement
SP  - S98
EP  - S99
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4459
ER  - 

@conference{
author = "Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "The human population is exposed to a vast number of chemicals that are known or
suspected endocrine disruptors. Although thresholds are mainly determined concerning a
single compound, in real life we are indeed exposed to multiple chemicals in mixtures, i.e.
toxic cocktails. The focus of this research was to determine the effects that toxic cocktails of
metal(oid)s have on human endocrine health The study involved 435 participants from the
general population of Serbia (218 women and 217 men) from five different cohorts (prostate
and testes cancer patients, breast cancer and benign breast dysplasia, pancreatic cancer,
thyroid, and metabolic disorders patients, and healthy volunteers). Blood cadmium (Cd),
lead (Pb), arsenic (As), mercury (Hg), nickel (Ni), and chromium (Cr) levels and serum levels
of various hormones were measured in all collected samples. The statistical analyses were
performed using the R language while dose-response analysis was performed in PROAST
software. Levels estimated to produce the 10% extra risk of testosterone serum levels
disturbances were lower than median Hg levels measured in the general population. The
obtained results also provided support for the positive association between Pb exposure and
higher insulin levels. Similarly, the calculated levels that can produce 10% of extra risk for
the disturbances in free thyroxine levels were lower than the medium determined As levels.
These findings provide strong support for the endocrine-disrupting effects of the
investigated toxic cocktail of metal(oid)s present in our environment and suggest that
threshold values for such effects might be lower than those currently implemented., Opšta populacija je svakodnevno izložena velikom broju hemikalija za koje se zna ili se
sumnja da su endokrini ometači. Iako se referentne doze uglavnom određuju za pojedinačne
hemikalije, u stvarnom životu smo zapravo izloženi hemikalijama u smešama, odnosno
toksičnim koktelima. Fokus istraživanja bio je na utvrđivanju uticaja koje toksični koktel
metala(oida) imaju na endokrino zdravlje ljudi. Istraživanje je obuhvatilo 435 učesnika iz
opšte populacije Republike Srbije (218 žena i 217 muškaraca) iz pet različitih kohorti
(pacijenti sa: karcinomima prostate ili testisa, karcinomom dojke ili benignom displazijom
dojke, karcinomom pankreasa, poremećajima štitaste žlezde i metaboličkim poremeć ajima,
te zdravi dobrovoljci). U prikupljenim uzorcima mereni su nivoi kadmijuma (Cd), olova (Pb),
arsena (As), žive (Hg), nikla (Ni) i hroma (Cr) u krvi, kao i nivoi različitih hormona u serumu.
Statističke analize su obavljene korišćenjem R statističkog paketa, dok je doza-odgovor
analiza vršena u PROAST softveru (RIVM, Holandija). Nivoi za koje se procenjuje da dovode
do dodatnog rizika od 10% za nastanak poremeć aja nivoa testosterona u serumu bili su niži
od medijane izmerenih nivoa Hg kod ispitanika. Dobijeni rezultati su takođe pružili podršku
postojanju veze između nivoa izloženosti Pb i viših nivoa insulina. Slično, izračunati nivoi As
u krvi koji mogu da izazovu 10% dodatnog rizika za poremeć aje nivoa slobodnog tiroksina
bili su niži od izračunate medijane za nivoe ovog metaloida u krvi. Ovi nalazi pružaju dokaze
o endokrinim efektima ispitivanog koktela toksičnih metal(oid)a i sugerišu da bi granične
vrednosti za takve efekte mogle biti niže od onih koje se trenutno primenjuju.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Decoding the role of toxic coctails of metals in endocrine health: the study in the general population of the Republic of Serbia, Dekodiranje uloge koktela toksičnih metala u endokrinom zdravlju: studija na opštoj populaciji Republike Srbije",
volume = "72",
number = "4 suplement",
pages = "S98-S99",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4459"
}

Buha-Đorđević, A.. (2022). Decoding the role of toxic coctails of metals in endocrine health: the study in the general population of the Republic of Serbia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S98-S99.
https://hdl.handle.net/21.15107/rcub_farfar_4459

Buha-Đorđević A. Decoding the role of toxic coctails of metals in endocrine health: the study in the general population of the Republic of Serbia. in Arhiv za farmaciju. 2022;72(4 suplement):S98-S99.
https://hdl.handle.net/21.15107/rcub_farfar_4459 .

Buha-Đorđević, Aleksandra, "Decoding the role of toxic coctails of metals in endocrine health: the study in the general population of the Republic of Serbia" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S98-S99,
https://hdl.handle.net/21.15107/rcub_farfar_4459 .

TY  - JOUR
AU  - Anđelković, Milena
AU  - Kačavenda, Elena
AU  - Javorac, Dragana
AU  - Antonijević-Miljaković, Evica
AU  - Marić, Đurđica
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Ćurčić, Marijana
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4074
AB  - Cadmium (Cd), one of the most abundant environmental pollutants, is considered to have endocrine disrupting properties. However, data on the dose-response relationship between Cd dose and levels of hormones have been insufficiently studied, especially in human data sets. Thus, the aim of this study was to determine the possibility of analyzing data obtained from a case- control study in female patients with benign/malignant breast tumors, using the Benchmark dose (BMD) concept. The collected data on Cd levels in breast tissue and estrogen serum levels were processed in PROAST software using different variables. The dose-response relationship between the internal dose of Cd and estradiol levels in the serum was investigated and BMD intervals were calculated. The dose-response relationship between the Cd concentration in breast tissue and the estradiol serum level was shown, indicating lower estradiol serum levels as a consequence of higher Cd concentrations in breast tissue. As one of the few studies analyzing human data using the BMD approach, these findings could have a pivotal role in dose response analysis of data collected from human studies.
AB  - Kadmijum (Cd), jedan od najzastupljenijih zagađivača životne sredine, dokazan je endokrini ometač. Međutim, podaci o postojanju odnosa između doze Cd i odgovora-nivoa hormona nisu dovoljno istraženi, posebno podaci sakupljeni iz studija na ljudima. Stoga je cilj ove studije bio da se utvrdi mogućnost analize podataka dobijenih iz studije slučaja-kontrole kod pacijentkinja sa benignim/malignim tumorom dojke, primenom koncepta Benčmark doze (BMD). Prikupljeni podaci o nivoima Cd u tkivu dojke i serumskim nivoima estrogena obrađeni su u PROAST softveru uz korišćenje različitih varijabli. Ispitivan je odnos doza-odgovor između unutrašnje doze Cd (koncentracije u tkivu dojke) i estradiola u serumu i izračunati BMD intervali. Utvrđeno je postojanje odnosa između koncentracije Cd u tkivu dojke i nivoa estradiola u serumu koje ukazuje na niže nivoe estradiola u serumu kao posledica veće koncentracije Cd u tkivu dojke. Kao jedno od retkih istraživanja ovog tipa, dobijeni rezultati mogli bi predstavljati početak otkrivanja mogućnosti analize podataka prikupljenih u studijama na ljudima primenom BMD pristupa.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Cadmium levels in human breast tissue and
estradiol serum levels:
Is there a connection?
T1  - Nivoi kadmijuma u humanom tkivu dojke i nivoi
estradiola u serumu:
Postoji li veza?
VL  - 71
IS  - 6
SP  - 581
EP  - 595
DO  - 10.5937/ARHFARM71-34280
ER  - 

@article{
author = "Anđelković, Milena and Kačavenda, Elena and Javorac, Dragana and Antonijević-Miljaković, Evica and Marić, Đurđica and Baralić, Katarina and Đukić-Ćosić, Danijela and Ćurčić, Marijana and Antonijević, Biljana and Bulat, Zorica",
year = "2021",
abstract = "Cadmium (Cd), one of the most abundant environmental pollutants, is considered to have endocrine disrupting properties. However, data on the dose-response relationship between Cd dose and levels of hormones have been insufficiently studied, especially in human data sets. Thus, the aim of this study was to determine the possibility of analyzing data obtained from a case- control study in female patients with benign/malignant breast tumors, using the Benchmark dose (BMD) concept. The collected data on Cd levels in breast tissue and estrogen serum levels were processed in PROAST software using different variables. The dose-response relationship between the internal dose of Cd and estradiol levels in the serum was investigated and BMD intervals were calculated. The dose-response relationship between the Cd concentration in breast tissue and the estradiol serum level was shown, indicating lower estradiol serum levels as a consequence of higher Cd concentrations in breast tissue. As one of the few studies analyzing human data using the BMD approach, these findings could have a pivotal role in dose response analysis of data collected from human studies., Kadmijum (Cd), jedan od najzastupljenijih zagađivača životne sredine, dokazan je endokrini ometač. Međutim, podaci o postojanju odnosa između doze Cd i odgovora-nivoa hormona nisu dovoljno istraženi, posebno podaci sakupljeni iz studija na ljudima. Stoga je cilj ove studije bio da se utvrdi mogućnost analize podataka dobijenih iz studije slučaja-kontrole kod pacijentkinja sa benignim/malignim tumorom dojke, primenom koncepta Benčmark doze (BMD). Prikupljeni podaci o nivoima Cd u tkivu dojke i serumskim nivoima estrogena obrađeni su u PROAST softveru uz korišćenje različitih varijabli. Ispitivan je odnos doza-odgovor između unutrašnje doze Cd (koncentracije u tkivu dojke) i estradiola u serumu i izračunati BMD intervali. Utvrđeno je postojanje odnosa između koncentracije Cd u tkivu dojke i nivoa estradiola u serumu koje ukazuje na niže nivoe estradiola u serumu kao posledica veće koncentracije Cd u tkivu dojke. Kao jedno od retkih istraživanja ovog tipa, dobijeni rezultati mogli bi predstavljati početak otkrivanja mogućnosti analize podataka prikupljenih u studijama na ljudima primenom BMD pristupa.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Cadmium levels in human breast tissue and
estradiol serum levels:
Is there a connection?, Nivoi kadmijuma u humanom tkivu dojke i nivoi
estradiola u serumu:
Postoji li veza?",
volume = "71",
number = "6",
pages = "581-595",
doi = "10.5937/ARHFARM71-34280"
}

Anđelković, M., Kačavenda, E., Javorac, D., Antonijević-Miljaković, E., Marić, Đ., Baralić, K., Đukić-Ćosić, D., Ćurčić, M., Antonijević, B.,& Bulat, Z.. (2021). Cadmium levels in human breast tissue and
estradiol serum levels:
Is there a connection?. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 71(6), 581-595.
https://doi.org/10.5937/ARHFARM71-34280

Anđelković M, Kačavenda E, Javorac D, Antonijević-Miljaković E, Marić Đ, Baralić K, Đukić-Ćosić D, Ćurčić M, Antonijević B, Bulat Z. Cadmium levels in human breast tissue and
estradiol serum levels:
Is there a connection?. in Arhiv za farmaciju. 2021;71(6):581-595.
doi:10.5937/ARHFARM71-34280 .

Anđelković, Milena, Kačavenda, Elena, Javorac, Dragana, Antonijević-Miljaković, Evica, Marić, Đurđica, Baralić, Katarina, Đukić-Ćosić, Danijela, Ćurčić, Marijana, Antonijević, Biljana, Bulat, Zorica, "Cadmium levels in human breast tissue and
estradiol serum levels:
Is there a connection?" in Arhiv za farmaciju, 71, no. 6 (2021):581-595,
https://doi.org/10.5937/ARHFARM71-34280 . .

TY  - JOUR
AU  - Buha, Aleksandra
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Tinkov, Alexey
AU  - Panieri, Emiliano
AU  - Saso, Luciano
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3824
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resis-tance to oxidants, serves as one of the key defensive factors against a range of pathological processessuch as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals.An increase in human exposure to toxic metals via air, food, and water has been recently observed,which is mainly due to anthropogenic activities. The relationship between environmental exposureto heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well asmetaloid arsenic (As), and transition metal chromium (Cr), and the development of various humandiseases has been extensively investigated.  Their ability to induce reactive oxygen species (ROS)production through direct and indirect actions and cause oxidative stress has been documentedin various organs.  Taking into account that Nrf2 signaling represents an important pathway inmaintaining antioxidant balance, recent research indicates that it can play a dual role depending onthe specific biological context. On one side, Nrf2 represents a potential crucial protective mechanismin metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogen-esis under conditions of prolonged exposure and continuous activation. Thus, this review aims tosummarize the state-of-the-art knowledge regarding the functional interrelation between the toxicmetals and Nrf2 signaling.
PB  - MDPI AG
T2  - Antioxidants
T1  - The role of toxic metals and metalloids in nrf2 signaling
VL  - 10
IS  - 5
DO  - 10.3390/antiox10050630
ER  - 

@article{
author = "Buha, Aleksandra and Baralić, Katarina and Đukić-Ćosić, Danijela and Bulat, Zorica and Tinkov, Alexey and Panieri, Emiliano and Saso, Luciano",
year = "2021",
abstract = "Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resis-tance to oxidants, serves as one of the key defensive factors against a range of pathological processessuch as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals.An increase in human exposure to toxic metals via air, food, and water has been recently observed,which is mainly due to anthropogenic activities. The relationship between environmental exposureto heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well asmetaloid arsenic (As), and transition metal chromium (Cr), and the development of various humandiseases has been extensively investigated.  Their ability to induce reactive oxygen species (ROS)production through direct and indirect actions and cause oxidative stress has been documentedin various organs.  Taking into account that Nrf2 signaling represents an important pathway inmaintaining antioxidant balance, recent research indicates that it can play a dual role depending onthe specific biological context. On one side, Nrf2 represents a potential crucial protective mechanismin metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogen-esis under conditions of prolonged exposure and continuous activation. Thus, this review aims tosummarize the state-of-the-art knowledge regarding the functional interrelation between the toxicmetals and Nrf2 signaling.",
publisher = "MDPI AG",
journal = "Antioxidants",
title = "The role of toxic metals and metalloids in nrf2 signaling",
volume = "10",
number = "5",
doi = "10.3390/antiox10050630"
}

Buha, A., Baralić, K., Đukić-Ćosić, D., Bulat, Z., Tinkov, A., Panieri, E.,& Saso, L.. (2021). The role of toxic metals and metalloids in nrf2 signaling. in Antioxidants
MDPI AG., 10(5).
https://doi.org/10.3390/antiox10050630

Buha A, Baralić K, Đukić-Ćosić D, Bulat Z, Tinkov A, Panieri E, Saso L. The role of toxic metals and metalloids in nrf2 signaling. in Antioxidants. 2021;10(5).
doi:10.3390/antiox10050630 .

Buha, Aleksandra, Baralić, Katarina, Đukić-Ćosić, Danijela, Bulat, Zorica, Tinkov, Alexey, Panieri, Emiliano, Saso, Luciano, "The role of toxic metals and metalloids in nrf2 signaling" in Antioxidants, 10, no. 5 (2021),
https://doi.org/10.3390/antiox10050630 . .

TY  - JOUR
AU  - Tinkov, Alexey
AU  - Nguyen, Thuy
AU  - Santamaria, Abe
AU  - Bowman, Aaron
AU  - Buha-Đorđević, Aleksandra
AU  - Paoliello, Monica Maria
AU  - Skalny, Anatoly
AU  - Aschner, Michael
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3910
AB  - Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.
PB  - Springer
T2  - Archives of Toxicology
T1  - Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity
DO  - 10.1007/s00204-021-03048-6
ER  - 

@article{
author = "Tinkov, Alexey and Nguyen, Thuy and Santamaria, Abe and Bowman, Aaron and Buha-Đorđević, Aleksandra and Paoliello, Monica Maria and Skalny, Anatoly and Aschner, Michael",
year = "2021",
abstract = "Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.",
publisher = "Springer",
journal = "Archives of Toxicology",
title = "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity",
doi = "10.1007/s00204-021-03048-6"
}

Tinkov, A., Nguyen, T., Santamaria, A., Bowman, A., Buha-Đorđević, A., Paoliello, M. M., Skalny, A.,& Aschner, M.. (2021). Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology
Springer..
https://doi.org/10.1007/s00204-021-03048-6

Tinkov A, Nguyen T, Santamaria A, Bowman A, Buha-Đorđević A, Paoliello MM, Skalny A, Aschner M. Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology. 2021;.
doi:10.1007/s00204-021-03048-6 .

Tinkov, Alexey, Nguyen, Thuy, Santamaria, Abe, Bowman, Aaron, Buha-Đorđević, Aleksandra, Paoliello, Monica Maria, Skalny, Anatoly, Aschner, Michael, "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity" in Archives of Toxicology (2021),
https://doi.org/10.1007/s00204-021-03048-6 . .