Saso, Luciano

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orcid::0000-0003-4530-8706
  • Saso, Luciano (15)

Author's Bibliography

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

Vukelić, Dragana; Baralić, Katarina; Marić, Đurđica; Đukić-Ćosić, Danijela; Bulat, Zorica; Panieri, Emiliano; Saso, Luciano; Buha-Đorđević, Aleksandra

(Elsevier B.V., 2024)

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 . .

Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application

Brborić, Jasmina; Klisić, Aleksandra; Kotur-Stevuljević, Jelena; Delogu, Giovanna; Gjorgieva Ackova, Darinka; Kostić, Kristina; Dettori, Maria Antonietta; Fabbri, Davide; Carta, Paola; Saso, Luciano

(Termedia Publishing House, 2023)

TY  - JOUR
AU  - Brborić, Jasmina
AU  - Klisić, Aleksandra
AU  - Kotur-Stevuljević, Jelena
AU  - Delogu, Giovanna
AU  - Gjorgieva Ackova, Darinka
AU  - Kostić, Kristina
AU  - Dettori, Maria Antonietta
AU  - Fabbri, Davide
AU  - Carta, Paola
AU  - Saso, Luciano
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4964
AB  - Introduction: Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to perform in vitro screening of natural and natural-like phenol monomers and their C2-symmetric dimers (hydroxylated biphenyls) in order to identify those representatives whose pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods: Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of α-tocopherol, was used as a positive control. Results: In an assay consisting of pooled human serum, 6 of the 36 compounds showed significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27), whereas 4 showed extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising zingerone, dehydrozingerone, aurone, chalcone, and magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox’s activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions: In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for synthesis of novel polyphenolic molecules with potential therapeutic applications.
PB  - Termedia Publishing House
T2  - Archives of Medical Science
T1  - Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application
VL  - 19
IS  - 3
SP  - 651
EP  - 671
DO  - 10.5114/aoms/135379
ER  - 
@article{
author = "Brborić, Jasmina and Klisić, Aleksandra and Kotur-Stevuljević, Jelena and Delogu, Giovanna and Gjorgieva Ackova, Darinka and Kostić, Kristina and Dettori, Maria Antonietta and Fabbri, Davide and Carta, Paola and Saso, Luciano",
year = "2023",
abstract = "Introduction: Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to perform in vitro screening of natural and natural-like phenol monomers and their C2-symmetric dimers (hydroxylated biphenyls) in order to identify those representatives whose pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods: Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of α-tocopherol, was used as a positive control. Results: In an assay consisting of pooled human serum, 6 of the 36 compounds showed significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27), whereas 4 showed extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising zingerone, dehydrozingerone, aurone, chalcone, and magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox’s activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions: In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for synthesis of novel polyphenolic molecules with potential therapeutic applications.",
publisher = "Termedia Publishing House",
journal = "Archives of Medical Science",
title = "Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application",
volume = "19",
number = "3",
pages = "651-671",
doi = "10.5114/aoms/135379"
}
Brborić, J., Klisić, A., Kotur-Stevuljević, J., Delogu, G., Gjorgieva Ackova, D., Kostić, K., Dettori, M. A., Fabbri, D., Carta, P.,& Saso, L.. (2023). Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application. in Archives of Medical Science
Termedia Publishing House., 19(3), 651-671.
https://doi.org/10.5114/aoms/135379
Brborić J, Klisić A, Kotur-Stevuljević J, Delogu G, Gjorgieva Ackova D, Kostić K, Dettori MA, Fabbri D, Carta P, Saso L. Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application. in Archives of Medical Science. 2023;19(3):651-671.
doi:10.5114/aoms/135379 .
Brborić, Jasmina, Klisić, Aleksandra, Kotur-Stevuljević, Jelena, Delogu, Giovanna, Gjorgieva Ackova, Darinka, Kostić, Kristina, Dettori, Maria Antonietta, Fabbri, Davide, Carta, Paola, Saso, Luciano, "Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application" in Archives of Medical Science, 19, no. 3 (2023):651-671,
https://doi.org/10.5114/aoms/135379 . .
1
2
3

Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls

Kostić, Kristina; Brborić, Jasmina; Delogu, Giovanna; Simić, Milena; Samardžić, Stevan; Maksimović, Zoran; Dettori, Maria Antonietta; Fabbri, Davide; Kotur-Stevuljević, Jelena; Saso, Luciano

(MDPI, 2023)

TY  - JOUR
AU  - Kostić, Kristina
AU  - Brborić, Jasmina
AU  - Delogu, Giovanna
AU  - Simić, Milena
AU  - Samardžić, Stevan
AU  - Maksimović, Zoran
AU  - Dettori, Maria Antonietta
AU  - Fabbri, Davide
AU  - Kotur-Stevuljević, Jelena
AU  - Saso, Luciano
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4648
AB  - A comparative in vitro study of the antioxidant potential of natural phenols (zingerone, curcumin, raspberry ketone, magnolol) and their synthesized derivatives was performed. The antioxidant efficiency was evaluated in blood serum obtained from healthy individuals, by means of spectrophotometry, before and after the addition of pro-oxidant tert-butyl hydroperoxide (TBH). Moreover, the antioxidant effect of an equimolar mixture of curcumin and zingerone was investigated. Interpretation of our results reveals that in the blood serum of healthy individuals curcumin (C1), raspberry ketone (RK1), magnolol (M1) and synthesized derivative of zingerone (Z2) demonstrate remarkable antioxidant effects (p < 0.05). However, in the state of TBH-induced excessive oxidative stress natural magnolol and synthesized derivatives C1, Z1 and RK1 show powerful antioxidant activity and thus can be further investigated to obtain information about their metabolic transformations and their potential influence at the cellular level. Results obtained from measurements in an equimolar mixture of zingerone and curcumin indicate synergism (p < 0.05) between the two compounds. This combination is especially successful due to the fast and efficient neutralization of added pro-oxidant TBH. The commercial availability of turmeric and ginger and their frequent combined use in diet suggest ideas for further broader utilization of the beneficial synergistic effect of their phenolic components.
PB  - MDPI
T2  - Molecules
T1  - Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls
VL  - 28
IS  - 6
DO  - 10.3390/molecules28062646
ER  - 
@article{
author = "Kostić, Kristina and Brborić, Jasmina and Delogu, Giovanna and Simić, Milena and Samardžić, Stevan and Maksimović, Zoran and Dettori, Maria Antonietta and Fabbri, Davide and Kotur-Stevuljević, Jelena and Saso, Luciano",
year = "2023",
abstract = "A comparative in vitro study of the antioxidant potential of natural phenols (zingerone, curcumin, raspberry ketone, magnolol) and their synthesized derivatives was performed. The antioxidant efficiency was evaluated in blood serum obtained from healthy individuals, by means of spectrophotometry, before and after the addition of pro-oxidant tert-butyl hydroperoxide (TBH). Moreover, the antioxidant effect of an equimolar mixture of curcumin and zingerone was investigated. Interpretation of our results reveals that in the blood serum of healthy individuals curcumin (C1), raspberry ketone (RK1), magnolol (M1) and synthesized derivative of zingerone (Z2) demonstrate remarkable antioxidant effects (p < 0.05). However, in the state of TBH-induced excessive oxidative stress natural magnolol and synthesized derivatives C1, Z1 and RK1 show powerful antioxidant activity and thus can be further investigated to obtain information about their metabolic transformations and their potential influence at the cellular level. Results obtained from measurements in an equimolar mixture of zingerone and curcumin indicate synergism (p < 0.05) between the two compounds. This combination is especially successful due to the fast and efficient neutralization of added pro-oxidant TBH. The commercial availability of turmeric and ginger and their frequent combined use in diet suggest ideas for further broader utilization of the beneficial synergistic effect of their phenolic components.",
publisher = "MDPI",
journal = "Molecules",
title = "Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls",
volume = "28",
number = "6",
doi = "10.3390/molecules28062646"
}
Kostić, K., Brborić, J., Delogu, G., Simić, M., Samardžić, S., Maksimović, Z., Dettori, M. A., Fabbri, D., Kotur-Stevuljević, J.,& Saso, L.. (2023). Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls. in Molecules
MDPI., 28(6).
https://doi.org/10.3390/molecules28062646
Kostić K, Brborić J, Delogu G, Simić M, Samardžić S, Maksimović Z, Dettori MA, Fabbri D, Kotur-Stevuljević J, Saso L. Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls. in Molecules. 2023;28(6).
doi:10.3390/molecules28062646 .
Kostić, Kristina, Brborić, Jasmina, Delogu, Giovanna, Simić, Milena, Samardžić, Stevan, Maksimović, Zoran, Dettori, Maria Antonietta, Fabbri, Davide, Kotur-Stevuljević, Jelena, Saso, Luciano, "Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls" in Molecules, 28, no. 6 (2023),
https://doi.org/10.3390/molecules28062646 . .
2

PFAS Molecules: A Major Concern for the Human Health and the Environment

Panieri, Emiliano; Baralić, Katarina; Đukić-Ćosić, Danijela; Buha-Đorđević, Aleksandra; Saso, Luciano

(MDPI, 2022)

TY  - JOUR
AU  - Panieri, Emiliano
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Buha-Đorđević, Aleksandra
AU  - Saso, Luciano
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4354
AB  - Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.
PB  - MDPI
T2  - Toxics
T1  - PFAS Molecules: A Major Concern for the Human Health and the Environment
VL  - 10
IS  - 2
DO  - 10.3390/toxics10020044
ER  - 
@article{
author = "Panieri, Emiliano and Baralić, Katarina and Đukić-Ćosić, Danijela and Buha-Đorđević, Aleksandra and Saso, Luciano",
year = "2022",
abstract = "Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.",
publisher = "MDPI",
journal = "Toxics",
title = "PFAS Molecules: A Major Concern for the Human Health and the Environment",
volume = "10",
number = "2",
doi = "10.3390/toxics10020044"
}
Panieri, E., Baralić, K., Đukić-Ćosić, D., Buha-Đorđević, A.,& Saso, L.. (2022). PFAS Molecules: A Major Concern for the Human Health and the Environment. in Toxics
MDPI., 10(2).
https://doi.org/10.3390/toxics10020044
Panieri E, Baralić K, Đukić-Ćosić D, Buha-Đorđević A, Saso L. PFAS Molecules: A Major Concern for the Human Health and the Environment. in Toxics. 2022;10(2).
doi:10.3390/toxics10020044 .
Panieri, Emiliano, Baralić, Katarina, Đukić-Ćosić, Danijela, Buha-Đorđević, Aleksandra, Saso, Luciano, "PFAS Molecules: A Major Concern for the Human Health and the Environment" in Toxics, 10, no. 2 (2022),
https://doi.org/10.3390/toxics10020044 . .
118
87
75

The role of toxic metals and metalloids in nrf2 signaling

Buha, Aleksandra; Baralić, Katarina; Đukić-Ćosić, Danijela; Bulat, Zorica; Tinkov, Alexey; Panieri, Emiliano; Saso, Luciano

(MDPI AG, 2021)

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 . .
3
28
1
27

Potential applications of NRF2 modulators in cancer therapy

Panieri, Emiliano; Buha, Aleksandra; Telkoparan-Akillilar, Pelin; Cevik, Dilek; Kouretas, Demetrios; Veskoukis, Aristidis; Skaperda, Zoi; Tsatsakis, Aristidis; Wallace, David; Suzen, Sibel; Saso, Luciano

(MDPI, 2020)

TY  - JOUR
AU  - Panieri, Emiliano
AU  - Buha, Aleksandra
AU  - Telkoparan-Akillilar, Pelin
AU  - Cevik, Dilek
AU  - Kouretas, Demetrios
AU  - Veskoukis, Aristidis
AU  - Skaperda, Zoi
AU  - Tsatsakis, Aristidis
AU  - Wallace, David
AU  - Suzen, Sibel
AU  - Saso, Luciano
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3551
AB  - The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.
PB  - MDPI
T2  - Antioxidants
T1  - Potential applications of NRF2 modulators in cancer therapy
VL  - 9
IS  - 3
DO  - 10.3390/antiox9030193
ER  - 
@article{
author = "Panieri, Emiliano and Buha, Aleksandra and Telkoparan-Akillilar, Pelin and Cevik, Dilek and Kouretas, Demetrios and Veskoukis, Aristidis and Skaperda, Zoi and Tsatsakis, Aristidis and Wallace, David and Suzen, Sibel and Saso, Luciano",
year = "2020",
abstract = "The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Potential applications of NRF2 modulators in cancer therapy",
volume = "9",
number = "3",
doi = "10.3390/antiox9030193"
}
Panieri, E., Buha, A., Telkoparan-Akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A., Skaperda, Z., Tsatsakis, A., Wallace, D., Suzen, S.,& Saso, L.. (2020). Potential applications of NRF2 modulators in cancer therapy. in Antioxidants
MDPI., 9(3).
https://doi.org/10.3390/antiox9030193
Panieri E, Buha A, Telkoparan-Akillilar P, Cevik D, Kouretas D, Veskoukis A, Skaperda Z, Tsatsakis A, Wallace D, Suzen S, Saso L. Potential applications of NRF2 modulators in cancer therapy. in Antioxidants. 2020;9(3).
doi:10.3390/antiox9030193 .
Panieri, Emiliano, Buha, Aleksandra, Telkoparan-Akillilar, Pelin, Cevik, Dilek, Kouretas, Demetrios, Veskoukis, Aristidis, Skaperda, Zoi, Tsatsakis, Aristidis, Wallace, David, Suzen, Sibel, Saso, Luciano, "Potential applications of NRF2 modulators in cancer therapy" in Antioxidants, 9, no. 3 (2020),
https://doi.org/10.3390/antiox9030193 . .
6
102
55
93

Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents

Gjorgieva-Ackova, Darinka; Kotur-Stevuljević, Jelena; Mishra, Chandra Bhushan; Luthra, Pratibha Mehta; Saso, Luciano

(MDPI, Basel, 2019)

TY  - JOUR
AU  - Gjorgieva-Ackova, Darinka
AU  - Kotur-Stevuljević, Jelena
AU  - Mishra, Chandra Bhushan
AU  - Luthra, Pratibha Mehta
AU  - Saso, Luciano
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3327
AB  - Oxidant/antioxidant imbalance in the body has been implicated as one of the pathophysiological mechanisms leading to disease development. Therefore, we searched for a good antioxidant candidate that can be used as a therapeutic agent alone or in combination with other reported drugs. Earlier, we reported the A(2A) receptor antagonist properties of 7-Imino-3-substituted-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-urea derivatives (compounds 1-12) and the neuroprotective effect of compound 2. Therefore, in the present work, the antioxidant potential of compounds 1-12 was studied. Compounds 1-12 were screened using different (red/ox) tests, such as the Ferric Reducing Antioxidant Power (FRAP) assay, to determine total antioxidant activity, redox status tests (with and without prooxidants) such as Advanced Oxidation Protein Products (AOPP) and Total Oxidative Status (TOS) which measures H2O2 and lipid hydroperoxides, Paraoxonase-1 Enzyme Activity (PON1), Total SH-groups content, and Total Antioxidative Status (TAS) for antioxidant determination. The Prooxidative Score, Antioxidative Score, and Oxy Score were also calculated. From the obtained results, compounds 6 (8720 FRAP value and 39.31 Oxy Score) and 12 (7866 FRAP value and 36.41 Oxy Score) were found to possess significant antioxidant activity with reasonable potential for therapeutic activity.
PB  - MDPI, Basel
T2  - Applied Sciences, Basel
T1  - Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents
VL  - 9
IS  - 1
DO  - 10.3390/app9010113
ER  - 
@article{
author = "Gjorgieva-Ackova, Darinka and Kotur-Stevuljević, Jelena and Mishra, Chandra Bhushan and Luthra, Pratibha Mehta and Saso, Luciano",
year = "2019",
abstract = "Oxidant/antioxidant imbalance in the body has been implicated as one of the pathophysiological mechanisms leading to disease development. Therefore, we searched for a good antioxidant candidate that can be used as a therapeutic agent alone or in combination with other reported drugs. Earlier, we reported the A(2A) receptor antagonist properties of 7-Imino-3-substituted-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-urea derivatives (compounds 1-12) and the neuroprotective effect of compound 2. Therefore, in the present work, the antioxidant potential of compounds 1-12 was studied. Compounds 1-12 were screened using different (red/ox) tests, such as the Ferric Reducing Antioxidant Power (FRAP) assay, to determine total antioxidant activity, redox status tests (with and without prooxidants) such as Advanced Oxidation Protein Products (AOPP) and Total Oxidative Status (TOS) which measures H2O2 and lipid hydroperoxides, Paraoxonase-1 Enzyme Activity (PON1), Total SH-groups content, and Total Antioxidative Status (TAS) for antioxidant determination. The Prooxidative Score, Antioxidative Score, and Oxy Score were also calculated. From the obtained results, compounds 6 (8720 FRAP value and 39.31 Oxy Score) and 12 (7866 FRAP value and 36.41 Oxy Score) were found to possess significant antioxidant activity with reasonable potential for therapeutic activity.",
publisher = "MDPI, Basel",
journal = "Applied Sciences, Basel",
title = "Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents",
volume = "9",
number = "1",
doi = "10.3390/app9010113"
}
Gjorgieva-Ackova, D., Kotur-Stevuljević, J., Mishra, C. B., Luthra, P. M.,& Saso, L.. (2019). Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents. in Applied Sciences, Basel
MDPI, Basel., 9(1).
https://doi.org/10.3390/app9010113
Gjorgieva-Ackova D, Kotur-Stevuljević J, Mishra CB, Luthra PM, Saso L. Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents. in Applied Sciences, Basel. 2019;9(1).
doi:10.3390/app9010113 .
Gjorgieva-Ackova, Darinka, Kotur-Stevuljević, Jelena, Mishra, Chandra Bhushan, Luthra, Pratibha Mehta, Saso, Luciano, "Antioxidant Properties of Synthesized Bicyclic Thiazolopyrimidine Derivatives as Possible Therapeutic Agents" in Applied Sciences, Basel, 9, no. 1 (2019),
https://doi.org/10.3390/app9010113 . .
9
3
9

In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole

Đukić, Mirjana; Fesatidou, Mara; Xenikakis, Iakovos; Geronikaki, Athina; Angelova, Violina T.; Savić, Vladimir; Pasić, Marta; Krilović, Branislav; Đukić, Dušan; Gobeljić, Borko; Pavlica, Marina; Đurić, Ana; Stanojević, Ivan; Vojvodić, Danilo; Saso, Luciano

(Elsevier Ireland Ltd, Clare, 2018)

TY  - JOUR
AU  - Đukić, Mirjana
AU  - Fesatidou, Mara
AU  - Xenikakis, Iakovos
AU  - Geronikaki, Athina
AU  - Angelova, Violina T.
AU  - Savić, Vladimir
AU  - Pasić, Marta
AU  - Krilović, Branislav
AU  - Đukić, Dušan
AU  - Gobeljić, Borko
AU  - Pavlica, Marina
AU  - Đurić, Ana
AU  - Stanojević, Ivan
AU  - Vojvodić, Danilo
AU  - Saso, Luciano
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3154
AB  - The initial steps in preclinical drug developing research concern the synthesis of new compounds for specific therapeutic use which needs to be confirmed by in vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4-thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2-adamantylthiazol[3,2-b] [1,2,4] triazol-6(5H) ones (5-8); and an ethylaminothiazole-based chalcone (9), were tested for antioxidant activity (AOA) by using three in vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive substances test). Compounds 1-4 and 9 in particular are newly synthesized compounds. Also, traditional antioxidants Vitamins E and C and alpha-lipoic acid (alpha-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E 2.99% and alpha-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; alpha-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated similar to 50%; 3 and 8 displayed similar to 38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, similar to 100%, unlike alpha-LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox reaction principles between these assays dictate different AOA outcomes for a single compound. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbonyl functional domains and chelating ligand properties of the thiazolidinone derivatives correlated with AOA.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole
VL  - 286
SP  - 119
EP  - 131
DO  - 10.1016/j.cbi.2018.03.013
ER  - 
@article{
author = "Đukić, Mirjana and Fesatidou, Mara and Xenikakis, Iakovos and Geronikaki, Athina and Angelova, Violina T. and Savić, Vladimir and Pasić, Marta and Krilović, Branislav and Đukić, Dušan and Gobeljić, Borko and Pavlica, Marina and Đurić, Ana and Stanojević, Ivan and Vojvodić, Danilo and Saso, Luciano",
year = "2018",
abstract = "The initial steps in preclinical drug developing research concern the synthesis of new compounds for specific therapeutic use which needs to be confirmed by in vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4-thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2-adamantylthiazol[3,2-b] [1,2,4] triazol-6(5H) ones (5-8); and an ethylaminothiazole-based chalcone (9), were tested for antioxidant activity (AOA) by using three in vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive substances test). Compounds 1-4 and 9 in particular are newly synthesized compounds. Also, traditional antioxidants Vitamins E and C and alpha-lipoic acid (alpha-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E 2.99% and alpha-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; alpha-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated similar to 50%; 3 and 8 displayed similar to 38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, similar to 100%, unlike alpha-LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox reaction principles between these assays dictate different AOA outcomes for a single compound. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbonyl functional domains and chelating ligand properties of the thiazolidinone derivatives correlated with AOA.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole",
volume = "286",
pages = "119-131",
doi = "10.1016/j.cbi.2018.03.013"
}
Đukić, M., Fesatidou, M., Xenikakis, I., Geronikaki, A., Angelova, V. T., Savić, V., Pasić, M., Krilović, B., Đukić, D., Gobeljić, B., Pavlica, M., Đurić, A., Stanojević, I., Vojvodić, D.,& Saso, L.. (2018). In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 286, 119-131.
https://doi.org/10.1016/j.cbi.2018.03.013
Đukić M, Fesatidou M, Xenikakis I, Geronikaki A, Angelova VT, Savić V, Pasić M, Krilović B, Đukić D, Gobeljić B, Pavlica M, Đurić A, Stanojević I, Vojvodić D, Saso L. In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole. in Chemico-Biological Interactions. 2018;286:119-131.
doi:10.1016/j.cbi.2018.03.013 .
Đukić, Mirjana, Fesatidou, Mara, Xenikakis, Iakovos, Geronikaki, Athina, Angelova, Violina T., Savić, Vladimir, Pasić, Marta, Krilović, Branislav, Đukić, Dušan, Gobeljić, Borko, Pavlica, Marina, Đurić, Ana, Stanojević, Ivan, Vojvodić, Danilo, Saso, Luciano, "In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole" in Chemico-Biological Interactions, 286 (2018):119-131,
https://doi.org/10.1016/j.cbi.2018.03.013 . .
80
44
82

Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium

Begić, Aida; Đurić, Ana; Ninković, Milica; Stevanović, Ivana; Đurđević, Dragan; Pavlović, Miloš; Jelić, Katarina; Pantelić, Ana; Zebić, Goran; Dejanović, Bratislav; Stanojević, Ivan; Vojvodić, Danilo; Milosavljević, Petar; Đukić, Mirjana; Saso, Luciano

(Taylor & Francis Ltd, Abingdon, 2017)

TY  - JOUR
AU  - Begić, Aida
AU  - Đurić, Ana
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Đurđević, Dragan
AU  - Pavlović, Miloš
AU  - Jelić, Katarina
AU  - Pantelić, Ana
AU  - Zebić, Goran
AU  - Dejanović, Bratislav
AU  - Stanojević, Ivan
AU  - Vojvodić, Danilo
AU  - Milosavljević, Petar
AU  - Đukić, Mirjana
AU  - Saso, Luciano
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2963
AB  - Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O-2(center dot-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium
VL  - 32
IS  - 1
SP  - 478
EP  - 489
DO  - 10.1080/14756366.2016.1261132
ER  - 
@article{
author = "Begić, Aida and Đurić, Ana and Ninković, Milica and Stevanović, Ivana and Đurđević, Dragan and Pavlović, Miloš and Jelić, Katarina and Pantelić, Ana and Zebić, Goran and Dejanović, Bratislav and Stanojević, Ivan and Vojvodić, Danilo and Milosavljević, Petar and Đukić, Mirjana and Saso, Luciano",
year = "2017",
abstract = "Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O-2(center dot-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium",
volume = "32",
number = "1",
pages = "478-489",
doi = "10.1080/14756366.2016.1261132"
}
Begić, A., Đurić, A., Ninković, M., Stevanović, I., Đurđević, D., Pavlović, M., Jelić, K., Pantelić, A., Zebić, G., Dejanović, B., Stanojević, I., Vojvodić, D., Milosavljević, P., Đukić, M.,& Saso, L.. (2017). Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium. in Journal of Enzyme Inhibition and Medicinal Chemistry
Taylor & Francis Ltd, Abingdon., 32(1), 478-489.
https://doi.org/10.1080/14756366.2016.1261132
Begić A, Đurić A, Ninković M, Stevanović I, Đurđević D, Pavlović M, Jelić K, Pantelić A, Zebić G, Dejanović B, Stanojević I, Vojvodić D, Milosavljević P, Đukić M, Saso L. Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2017;32(1):478-489.
doi:10.1080/14756366.2016.1261132 .
Begić, Aida, Đurić, Ana, Ninković, Milica, Stevanović, Ivana, Đurđević, Dragan, Pavlović, Miloš, Jelić, Katarina, Pantelić, Ana, Zebić, Goran, Dejanović, Bratislav, Stanojević, Ivan, Vojvodić, Danilo, Milosavljević, Petar, Đukić, Mirjana, Saso, Luciano, "Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium" in Journal of Enzyme Inhibition and Medicinal Chemistry, 32, no. 1 (2017):478-489,
https://doi.org/10.1080/14756366.2016.1261132 . .
11
6
11

The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue

Begić, Aida; Đurić, Ana; Gobeljić, Borko; Stevanović, Ivana; Lukić, Vera; Stanojević, Ivan; Ninković, Milica; Saso, Luciano; Vojvodić, Danilo; Đukić, Mirjana

(Akademiai Kiado Rt, Budapest, 2017)

TY  - JOUR
AU  - Begić, Aida
AU  - Đurić, Ana
AU  - Gobeljić, Borko
AU  - Stevanović, Ivana
AU  - Lukić, Vera
AU  - Stanojević, Ivan
AU  - Ninković, Milica
AU  - Saso, Luciano
AU  - Vojvodić, Danilo
AU  - Đukić, Mirjana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2952
AB  - The aim of our work was to optimize and apply simple high-performance liquid chromatography method with ultraviolet detection (HPLC-UV) for simultaneous determination of reduced (GSH) and oxidized (GSSG) glutathione in biological matrix (specifically, the rat liver tissue was used herein), since the ratio between oxidized and reduced glutathione forms (GSSG-GSH) has been recognized as an important biological marker of oxidatively depleted GSH in oxidative stress (OS)-associated diseases and poisonings. An isocratic chromatographic separation of GSH and GSSG (2.8 min and 6.3 min, respectively) was performed with the mobile phase consisted of sodium perchlorate solution (pH adjusted to 2.8) at flow rate of 1 mL min(-1), detection set at 215 nm, and column temperature of 40 degrees C. The method offers short run time, linearity in the range of 0.01-200 mu M concentration for both compounds (R-2 = 1), low limits of detection and quantification (GSH: 0.18 mu M and 0.56 mu M, GSSG: 0.52 mu M and 1.58 mu M, respectively), precision, accuracy (bias  lt 2%), and high reproducibility. Through suitable sample handling, an overestimation of GSSG was prevented. High recovery (>99%) was achieved. The method was successfully applied for the analysis of GSH and GSSG in liver homogenates of Wistar rats intraperitoneally exposed to cadmium (Cd) (1 mg kg(-1) CdCl2/21 days). Regardless of other Cd-mediated hepatotoxicity mechanisms, herein, we have exclusively interpreted/emphasized oxidative GSH depletion. The presented method is acceptable for a routine analysis of GSH and GSSG in biological matrix, while the calculated ratio GSSG-GSH is considered as a valuable OS marker.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue
VL  - 29
IS  - 1
SP  - 67
EP  - 84
DO  - 10.1556/1326.2017.29.1.5
ER  - 
@article{
author = "Begić, Aida and Đurić, Ana and Gobeljić, Borko and Stevanović, Ivana and Lukić, Vera and Stanojević, Ivan and Ninković, Milica and Saso, Luciano and Vojvodić, Danilo and Đukić, Mirjana",
year = "2017",
abstract = "The aim of our work was to optimize and apply simple high-performance liquid chromatography method with ultraviolet detection (HPLC-UV) for simultaneous determination of reduced (GSH) and oxidized (GSSG) glutathione in biological matrix (specifically, the rat liver tissue was used herein), since the ratio between oxidized and reduced glutathione forms (GSSG-GSH) has been recognized as an important biological marker of oxidatively depleted GSH in oxidative stress (OS)-associated diseases and poisonings. An isocratic chromatographic separation of GSH and GSSG (2.8 min and 6.3 min, respectively) was performed with the mobile phase consisted of sodium perchlorate solution (pH adjusted to 2.8) at flow rate of 1 mL min(-1), detection set at 215 nm, and column temperature of 40 degrees C. The method offers short run time, linearity in the range of 0.01-200 mu M concentration for both compounds (R-2 = 1), low limits of detection and quantification (GSH: 0.18 mu M and 0.56 mu M, GSSG: 0.52 mu M and 1.58 mu M, respectively), precision, accuracy (bias  lt 2%), and high reproducibility. Through suitable sample handling, an overestimation of GSSG was prevented. High recovery (>99%) was achieved. The method was successfully applied for the analysis of GSH and GSSG in liver homogenates of Wistar rats intraperitoneally exposed to cadmium (Cd) (1 mg kg(-1) CdCl2/21 days). Regardless of other Cd-mediated hepatotoxicity mechanisms, herein, we have exclusively interpreted/emphasized oxidative GSH depletion. The presented method is acceptable for a routine analysis of GSH and GSSG in biological matrix, while the calculated ratio GSSG-GSH is considered as a valuable OS marker.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue",
volume = "29",
number = "1",
pages = "67-84",
doi = "10.1556/1326.2017.29.1.5"
}
Begić, A., Đurić, A., Gobeljić, B., Stevanović, I., Lukić, V., Stanojević, I., Ninković, M., Saso, L., Vojvodić, D.,& Đukić, M.. (2017). The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 29(1), 67-84.
https://doi.org/10.1556/1326.2017.29.1.5
Begić A, Đurić A, Gobeljić B, Stevanović I, Lukić V, Stanojević I, Ninković M, Saso L, Vojvodić D, Đukić M. The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue. in Acta Chromatographica. 2017;29(1):67-84.
doi:10.1556/1326.2017.29.1.5 .
Begić, Aida, Đurić, Ana, Gobeljić, Borko, Stevanović, Ivana, Lukić, Vera, Stanojević, Ivan, Ninković, Milica, Saso, Luciano, Vojvodić, Danilo, Đukić, Mirjana, "The Simple Isocratic HPLC-UV Method for the Simultaneous Determination of Reduced and Oxidized Glutathione in Animal Tissue" in Acta Chromatographica, 29, no. 1 (2017):67-84,
https://doi.org/10.1556/1326.2017.29.1.5 . .
11
4
12

Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold

Angelova, Violina T.; Valcheva, Violeta; Vassilev, Nikolay G.; Buyukliev, Rosen; Momekov, Georgi; Dimitrov, Ivan; Saso, Luciano; Đukić, Mirjana; Shivachev, Boris

(Pergamon-Elsevier Science Ltd, Oxford, 2017)

TY  - JOUR
AU  - Angelova, Violina T.
AU  - Valcheva, Violeta
AU  - Vassilev, Nikolay G.
AU  - Buyukliev, Rosen
AU  - Momekov, Georgi
AU  - Dimitrov, Ivan
AU  - Saso, Luciano
AU  - Đukić, Mirjana
AU  - Shivachev, Boris
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2940
AB  - This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 mu M), 7o (MIC 0.15 mu M) and 7k (MIC 0.17 mu M) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry Letters
T1  - Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold
VL  - 27
IS  - 2
SP  - 223
EP  - 227
DO  - 10.1016/j.bmcl.2016.11.071
ER  - 
@article{
author = "Angelova, Violina T. and Valcheva, Violeta and Vassilev, Nikolay G. and Buyukliev, Rosen and Momekov, Georgi and Dimitrov, Ivan and Saso, Luciano and Đukić, Mirjana and Shivachev, Boris",
year = "2017",
abstract = "This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 mu M), 7o (MIC 0.15 mu M) and 7k (MIC 0.17 mu M) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry Letters",
title = "Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold",
volume = "27",
number = "2",
pages = "223-227",
doi = "10.1016/j.bmcl.2016.11.071"
}
Angelova, V. T., Valcheva, V., Vassilev, N. G., Buyukliev, R., Momekov, G., Dimitrov, I., Saso, L., Đukić, M.,& Shivachev, B.. (2017). Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold. in Bioorganic & Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd, Oxford., 27(2), 223-227.
https://doi.org/10.1016/j.bmcl.2016.11.071
Angelova VT, Valcheva V, Vassilev NG, Buyukliev R, Momekov G, Dimitrov I, Saso L, Đukić M, Shivachev B. Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold. in Bioorganic & Medicinal Chemistry Letters. 2017;27(2):223-227.
doi:10.1016/j.bmcl.2016.11.071 .
Angelova, Violina T., Valcheva, Violeta, Vassilev, Nikolay G., Buyukliev, Rosen, Momekov, Georgi, Dimitrov, Ivan, Saso, Luciano, Đukić, Mirjana, Shivachev, Boris, "Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold" in Bioorganic & Medicinal Chemistry Letters, 27, no. 2 (2017):223-227,
https://doi.org/10.1016/j.bmcl.2016.11.071 . .
62
42
67

Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins

Aminjafari, Akram; Miroliaei, Mehran; Angelova, Violina T.; Emamzadeh, Rahman; Đukić, Mirjana; Đurić, Ana; Saso, Luciano

(Univ Catolica de Valparaiso, Valparaiso, 2016)

TY  - JOUR
AU  - Aminjafari, Akram
AU  - Miroliaei, Mehran
AU  - Angelova, Violina T.
AU  - Emamzadeh, Rahman
AU  - Đukić, Mirjana
AU  - Đurić, Ana
AU  - Saso, Luciano
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2679
AB  - Background: Synthesized aminocoumarins are heterocyclic compounds possessing potential for the treatment of insulin-dependent diabetes mellitus with unexplored anti-glycative action. Results: In this study 4-aminocoumarin derivatives (4-ACDs) were evaluated in vitro for antiglycation (AG) activities by using the human serum albumin (HSA)/glucose system, for 8 weeks of incubation. The glycation and conformational alteration of HSA in the presence of the tested compounds were evaluated by Congo red assay, fluorescence and circular dichroism spectroscopy. The antioxidant (AO) capacity were also tested by four different assays including: DPPH (2,2'-diphenyl-1-picrylhydrazyl radical), ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulphonate) diammonium salt), FRAP (ferric reducing antioxidant power) and beta-carotene-linoleic acid assay. The tested compounds showed AG and AO effects. The intensity of the accomplished AO potential is related to the type of the used assay. Significant alterations in the secondary (monitored by CD spectropolarimetry) and tertiary structure (assessed by spectrofluorimetry) of HSA upon glycation were mitigated by the 4-ACDs, suggesting their suppressive role in the late stage (post-Amadori) of the HSA glycation. Conclusions: By the analogues, in vitro ascertained AO and AG properties of 4-ACDmay be recognized as rationale for their protective role against oxidative changes of proteins, thereby precluding diabetic complications in humans.
PB  - Univ Catolica de Valparaiso, Valparaiso
T2  - Electronic Journal of Biotechnology
T1  - Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins
VL  - 24
SP  - 43
EP  - 48
DO  - 10.1016/j.ejbt.2016.08.004
ER  - 
@article{
author = "Aminjafari, Akram and Miroliaei, Mehran and Angelova, Violina T. and Emamzadeh, Rahman and Đukić, Mirjana and Đurić, Ana and Saso, Luciano",
year = "2016",
abstract = "Background: Synthesized aminocoumarins are heterocyclic compounds possessing potential for the treatment of insulin-dependent diabetes mellitus with unexplored anti-glycative action. Results: In this study 4-aminocoumarin derivatives (4-ACDs) were evaluated in vitro for antiglycation (AG) activities by using the human serum albumin (HSA)/glucose system, for 8 weeks of incubation. The glycation and conformational alteration of HSA in the presence of the tested compounds were evaluated by Congo red assay, fluorescence and circular dichroism spectroscopy. The antioxidant (AO) capacity were also tested by four different assays including: DPPH (2,2'-diphenyl-1-picrylhydrazyl radical), ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulphonate) diammonium salt), FRAP (ferric reducing antioxidant power) and beta-carotene-linoleic acid assay. The tested compounds showed AG and AO effects. The intensity of the accomplished AO potential is related to the type of the used assay. Significant alterations in the secondary (monitored by CD spectropolarimetry) and tertiary structure (assessed by spectrofluorimetry) of HSA upon glycation were mitigated by the 4-ACDs, suggesting their suppressive role in the late stage (post-Amadori) of the HSA glycation. Conclusions: By the analogues, in vitro ascertained AO and AG properties of 4-ACDmay be recognized as rationale for their protective role against oxidative changes of proteins, thereby precluding diabetic complications in humans.",
publisher = "Univ Catolica de Valparaiso, Valparaiso",
journal = "Electronic Journal of Biotechnology",
title = "Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins",
volume = "24",
pages = "43-48",
doi = "10.1016/j.ejbt.2016.08.004"
}
Aminjafari, A., Miroliaei, M., Angelova, V. T., Emamzadeh, R., Đukić, M., Đurić, A.,& Saso, L.. (2016). Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins. in Electronic Journal of Biotechnology
Univ Catolica de Valparaiso, Valparaiso., 24, 43-48.
https://doi.org/10.1016/j.ejbt.2016.08.004
Aminjafari A, Miroliaei M, Angelova VT, Emamzadeh R, Đukić M, Đurić A, Saso L. Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins. in Electronic Journal of Biotechnology. 2016;24:43-48.
doi:10.1016/j.ejbt.2016.08.004 .
Aminjafari, Akram, Miroliaei, Mehran, Angelova, Violina T., Emamzadeh, Rahman, Đukić, Mirjana, Đurić, Ana, Saso, Luciano, "Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins" in Electronic Journal of Biotechnology, 24 (2016):43-48,
https://doi.org/10.1016/j.ejbt.2016.08.004 . .
1
19
12
17

Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma

Jović, Milena; Cerović, Snežana; Zolotarevska, Lidija; Gačević, Milomir; Stanojević, Ivan; Miller, Karolina; Đukić, Mirjana; Saso, Luciano; Jauković, Ljiljana; Vojvodić, Danilo

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2016)

TY  - JOUR
AU  - Jović, Milena
AU  - Cerović, Snežana
AU  - Zolotarevska, Lidija
AU  - Gačević, Milomir
AU  - Stanojević, Ivan
AU  - Miller, Karolina
AU  - Đukić, Mirjana
AU  - Saso, Luciano
AU  - Jauković, Ljiljana
AU  - Vojvodić, Danilo
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2634
AB  - Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.
AB  - Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma
T1  - Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože
VL  - 73
IS  - 11
SP  - 1022
EP  - 1029
DO  - 10.2298/VSP150519119J
ER  - 
@article{
author = "Jović, Milena and Cerović, Snežana and Zolotarevska, Lidija and Gačević, Milomir and Stanojević, Ivan and Miller, Karolina and Đukić, Mirjana and Saso, Luciano and Jauković, Ljiljana and Vojvodić, Danilo",
year = "2016",
abstract = "Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI., Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma, Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože",
volume = "73",
number = "11",
pages = "1022-1029",
doi = "10.2298/VSP150519119J"
}
Jović, M., Cerović, S., Zolotarevska, L., Gačević, M., Stanojević, I., Miller, K., Đukić, M., Saso, L., Jauković, L.,& Vojvodić, D.. (2016). Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 73(11), 1022-1029.
https://doi.org/10.2298/VSP150519119J
Jović M, Cerović S, Zolotarevska L, Gačević M, Stanojević I, Miller K, Đukić M, Saso L, Jauković L, Vojvodić D. Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma. in Vojnosanitetski pregled. 2016;73(11):1022-1029.
doi:10.2298/VSP150519119J .
Jović, Milena, Cerović, Snežana, Zolotarevska, Lidija, Gačević, Milomir, Stanojević, Ivan, Miller, Karolina, Đukić, Mirjana, Saso, Luciano, Jauković, Ljiljana, Vojvodić, Danilo, "Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma" in Vojnosanitetski pregled, 73, no. 11 (2016):1022-1029,
https://doi.org/10.2298/VSP150519119J . .
1
1

Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety

Angelova, Violina T.; Vassilev, Nikolay G.; Nikolova-Mladenova, Boryana; Vitas, Jasmina; Malbasa, Radomir; Momekov, Georgi; Đukić, Mirjana; Saso, Luciano

(Springer Birkhauser, New York, 2016)

TY  - JOUR
AU  - Angelova, Violina T.
AU  - Vassilev, Nikolay G.
AU  - Nikolova-Mladenova, Boryana
AU  - Vitas, Jasmina
AU  - Malbasa, Radomir
AU  - Momekov, Georgi
AU  - Đukić, Mirjana
AU  - Saso, Luciano
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2760
AB  - A series of new hybrid molecules with a hydrazone fragment were synthesized and characterized by Fourier transform-infrared spectroscopy, nuclear magnetic resonance, mass spectrometry, and elemental analysis. The nuclear magnetic resonance spectra of the hydrazones 4a-c showed exchange of syn and antiperiplanar conformers around the amide bond, the more stable being the antiperiplanar one. The nuclear Overhauser effect spectroscopy (NOESY) spectra confirm E configuration around C=N bond. The tested compounds exhibited concentration-dependent cytotoxic effects against human tumor cell lines in a micromolar range (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay). Hydrazone 4a proved to be the most potent antiproliferative agent of the series. Within the antioxidant screening 8b exhibited the highest radical scavenging activity (% RSA max) and the largest rate constant for the reaction with 2,2-diphenyl-1-picrylhydrazyl.
PB  - Springer Birkhauser, New York
T2  - Medicinal Chemistry Research
T1  - Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety
VL  - 25
IS  - 9
SP  - 2082
EP  - 2092
DO  - 10.1007/s00044-016-1661-4
ER  - 
@article{
author = "Angelova, Violina T. and Vassilev, Nikolay G. and Nikolova-Mladenova, Boryana and Vitas, Jasmina and Malbasa, Radomir and Momekov, Georgi and Đukić, Mirjana and Saso, Luciano",
year = "2016",
abstract = "A series of new hybrid molecules with a hydrazone fragment were synthesized and characterized by Fourier transform-infrared spectroscopy, nuclear magnetic resonance, mass spectrometry, and elemental analysis. The nuclear magnetic resonance spectra of the hydrazones 4a-c showed exchange of syn and antiperiplanar conformers around the amide bond, the more stable being the antiperiplanar one. The nuclear Overhauser effect spectroscopy (NOESY) spectra confirm E configuration around C=N bond. The tested compounds exhibited concentration-dependent cytotoxic effects against human tumor cell lines in a micromolar range (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay). Hydrazone 4a proved to be the most potent antiproliferative agent of the series. Within the antioxidant screening 8b exhibited the highest radical scavenging activity (% RSA max) and the largest rate constant for the reaction with 2,2-diphenyl-1-picrylhydrazyl.",
publisher = "Springer Birkhauser, New York",
journal = "Medicinal Chemistry Research",
title = "Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety",
volume = "25",
number = "9",
pages = "2082-2092",
doi = "10.1007/s00044-016-1661-4"
}
Angelova, V. T., Vassilev, N. G., Nikolova-Mladenova, B., Vitas, J., Malbasa, R., Momekov, G., Đukić, M.,& Saso, L.. (2016). Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety. in Medicinal Chemistry Research
Springer Birkhauser, New York., 25(9), 2082-2092.
https://doi.org/10.1007/s00044-016-1661-4
Angelova VT, Vassilev NG, Nikolova-Mladenova B, Vitas J, Malbasa R, Momekov G, Đukić M, Saso L. Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety. in Medicinal Chemistry Research. 2016;25(9):2082-2092.
doi:10.1007/s00044-016-1661-4 .
Angelova, Violina T., Vassilev, Nikolay G., Nikolova-Mladenova, Boryana, Vitas, Jasmina, Malbasa, Radomir, Momekov, Georgi, Đukić, Mirjana, Saso, Luciano, "Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety" in Medicinal Chemistry Research, 25, no. 9 (2016):2082-2092,
https://doi.org/10.1007/s00044-016-1661-4 . .
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Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium

Đurić, Ana; Begić, Aida; Gobeljić, Borko; Stanojević, Ivan; Ninković, Milica; Vojvodić, Danilo; Pantelić, Ana; Zebić, Goran; Prokić, Vera; Dejanović, Bratislav; Stojanović, Ivana; Pavlica, Marina; Đukić, Dušan; Saso, Luciano; Đurđević, Dragan; Pavlović, Miloš; Topić, Aleksandra; Vujanović, Dragana; Stevnović, Ivana; Đukić, Mirjana

(Pergamon-Elsevier Science Ltd, Oxford, 2015)

TY  - JOUR
AU  - Đurić, Ana
AU  - Begić, Aida
AU  - Gobeljić, Borko
AU  - Stanojević, Ivan
AU  - Ninković, Milica
AU  - Vojvodić, Danilo
AU  - Pantelić, Ana
AU  - Zebić, Goran
AU  - Prokić, Vera
AU  - Dejanović, Bratislav
AU  - Stojanović, Ivana
AU  - Pavlica, Marina
AU  - Đukić, Dušan
AU  - Saso, Luciano
AU  - Đurđević, Dragan
AU  - Pavlović, Miloš
AU  - Topić, Aleksandra
AU  - Vujanović, Dragana
AU  - Stevnović, Ivana
AU  - Đukić, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2364
AB  - The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 121 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O-2(center dot-)) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium
VL  - 86
SP  - 25
EP  - 33
DO  - 10.1016/j.fct.2015.09.004
ER  - 
@article{
author = "Đurić, Ana and Begić, Aida and Gobeljić, Borko and Stanojević, Ivan and Ninković, Milica and Vojvodić, Danilo and Pantelić, Ana and Zebić, Goran and Prokić, Vera and Dejanović, Bratislav and Stojanović, Ivana and Pavlica, Marina and Đukić, Dušan and Saso, Luciano and Đurđević, Dragan and Pavlović, Miloš and Topić, Aleksandra and Vujanović, Dragana and Stevnović, Ivana and Đukić, Mirjana",
year = "2015",
abstract = "The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 121 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O-2(center dot-)) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium",
volume = "86",
pages = "25-33",
doi = "10.1016/j.fct.2015.09.004"
}
Đurić, A., Begić, A., Gobeljić, B., Stanojević, I., Ninković, M., Vojvodić, D., Pantelić, A., Zebić, G., Prokić, V., Dejanović, B., Stojanović, I., Pavlica, M., Đukić, D., Saso, L., Đurđević, D., Pavlović, M., Topić, A., Vujanović, D., Stevnović, I.,& Đukić, M.. (2015). Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium. in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 86, 25-33.
https://doi.org/10.1016/j.fct.2015.09.004
Đurić A, Begić A, Gobeljić B, Stanojević I, Ninković M, Vojvodić D, Pantelić A, Zebić G, Prokić V, Dejanović B, Stojanović I, Pavlica M, Đukić D, Saso L, Đurđević D, Pavlović M, Topić A, Vujanović D, Stevnović I, Đukić M. Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium. in Food and Chemical Toxicology. 2015;86:25-33.
doi:10.1016/j.fct.2015.09.004 .
Đurić, Ana, Begić, Aida, Gobeljić, Borko, Stanojević, Ivan, Ninković, Milica, Vojvodić, Danilo, Pantelić, Ana, Zebić, Goran, Prokić, Vera, Dejanović, Bratislav, Stojanović, Ivana, Pavlica, Marina, Đukić, Dušan, Saso, Luciano, Đurđević, Dragan, Pavlović, Miloš, Topić, Aleksandra, Vujanović, Dragana, Stevnović, Ivana, Đukić, Mirjana, "Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium" in Food and Chemical Toxicology, 86 (2015):25-33,
https://doi.org/10.1016/j.fct.2015.09.004 . .
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