TY  - JOUR
AU  - Platanić Arizanović, Lena
AU  - Nikolić-Kokić, Aleksandra
AU  - Brkljačić, Jelena
AU  - Tatalović, Nikola
AU  - Miler, Marko
AU  - Oreščanin-Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško P.
AU  - Spasić, Snežana
AU  - Miljević, Čedo
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33234086
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/4778
AB  - Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.
PB  - Taylor and Francis
T2  - Journal of Toxicology and Environmental Health. Part A
T2  - Journal of Toxicology and Environmental Health. Part AJ Toxicol Environ Health A
T1  - Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction
VL  - 84
IS  - 4
SP  - 173
EP  - 182
DO  - 10.1080/15287394.2020.1844827
ER  - 

@article{
author = "Platanić Arizanović, Lena and Nikolić-Kokić, Aleksandra and Brkljačić, Jelena and Tatalović, Nikola and Miler, Marko and Oreščanin-Dušić, Zorana and Vidonja Uzelac, Teodora and Nikolić, Milan and Milošević, Verica and Blagojević, Duško P. and Spasić, Snežana and Miljević, Čedo",
year = "2021",
abstract = "Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.",
publisher = "Taylor and Francis",
journal = "Journal of Toxicology and Environmental Health. Part A, Journal of Toxicology and Environmental Health. Part AJ Toxicol Environ Health A",
title = "Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction",
volume = "84",
number = "4",
pages = "173-182",
doi = "10.1080/15287394.2020.1844827"
}

Platanić Arizanović, L., Nikolić-Kokić, A., Brkljačić, J., Tatalović, N., Miler, M., Oreščanin-Dušić, Z., Vidonja Uzelac, T., Nikolić, M., Milošević, V., Blagojević, D. P., Spasić, S.,& Miljević, Č.. (2021). Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction. in Journal of Toxicology and Environmental Health. Part A
Taylor and Francis., 84(4), 173-182.
https://doi.org/10.1080/15287394.2020.1844827

Platanić Arizanović L, Nikolić-Kokić A, Brkljačić J, Tatalović N, Miler M, Oreščanin-Dušić Z, Vidonja Uzelac T, Nikolić M, Milošević V, Blagojević DP, Spasić S, Miljević Č. Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction. in Journal of Toxicology and Environmental Health. Part A. 2021;84(4):173-182.
doi:10.1080/15287394.2020.1844827 .

Platanić Arizanović, Lena, Nikolić-Kokić, Aleksandra, Brkljačić, Jelena, Tatalović, Nikola, Miler, Marko, Oreščanin-Dušić, Zorana, Vidonja Uzelac, Teodora, Nikolić, Milan, Milošević, Verica, Blagojević, Duško P., Spasić, Snežana, Miljević, Čedo, "Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction" in Journal of Toxicology and Environmental Health. Part A, 84, no. 4 (2021):173-182,
https://doi.org/10.1080/15287394.2020.1844827 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Nestorov, Jelena
AU  - Mijović, Milica
AU  - Mijušković, Ana
AU  - Miler, Marko
AU  - Oreščanin-Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško P.
AU  - Spasic, Mihajlo
AU  - Miljević, Čedo
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2206
AB  - Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity.Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- , tumor necrosis factor alpha.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Toxicology and Environmental Health. Part A
T1  - Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
VL  - 81
IS  - 17
SP  - 844
EP  - 853
DO  - 10.1080/15287394.2018.1495587
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Nestorov, Jelena and Mijović, Milica and Mijušković, Ana and Miler, Marko and Oreščanin-Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško P. and Spasic, Mihajlo and Miljević, Čedo",
year = "2018",
abstract = "Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity.Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- , tumor necrosis factor alpha.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Toxicology and Environmental Health. Part A",
title = "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function",
volume = "81",
number = "17",
pages = "844-853",
doi = "10.1080/15287394.2018.1495587"
}

Nikolić-Kokić, A., Tatalović, N., Nestorov, J., Mijović, M., Mijušković, A., Miler, M., Oreščanin-Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D. P., Spasic, M.,& Miljević, Č.. (2018). Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health. Part A
Taylor & Francis Inc, Philadelphia., 81(17), 844-853.
https://doi.org/10.1080/15287394.2018.1495587

Nikolić-Kokić A, Tatalović N, Nestorov J, Mijović M, Mijušković A, Miler M, Oreščanin-Dušić Z, Nikolić M, Milošević V, Blagojević DP, Spasic M, Miljević Č. Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health. Part A. 2018;81(17):844-853.
doi:10.1080/15287394.2018.1495587 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Nestorov, Jelena, Mijović, Milica, Mijušković, Ana, Miler, Marko, Oreščanin-Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško P., Spasic, Mihajlo, Miljević, Čedo, "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function" in Journal of Toxicology and Environmental Health. Part A, 81, no. 17 (2018):844-853,
https://doi.org/10.1080/15287394.2018.1495587 . .