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dc.creatorPlatanović Arizanović, Lena
dc.creatorNikolić-Kokić, Aleksandra
dc.creatorBrkljačić, Jelena
dc.creatorTatalović, Nikola
dc.creatorMiler, Marko
dc.creatorOreščanin-Dušić, Zorana
dc.creatorVidonja Uzelac, Teodora
dc.creatorNikolić, Milan
dc.creatorMilošević, Verica
dc.creatorBlagojević, Duško
dc.creatorSpasić, Snežana
dc.creatorMiljević, Čedo
dc.date.accessioned2020-12-03T20:00:44Z
dc.date.available2020-12-03T20:00:44Z
dc.date.issued2021
dc.identifier.issn1528-7394
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/3967
dc.description.abstractChronic 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.en
dc.language.isoensr
dc.publisherTaylor & Francissr
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200007/RS//sr
dc.rightsrestrictedAccesssr
dc.sourceJournal of Toxicology and Environmental Health, Part Asr
dc.subjectClozapinesr
dc.subjectsertindolesr
dc.subjectziprasidonesr
dc.subjectantioxidative enzymessr
dc.subjectliversr
dc.titleEffects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunctionen
dc.typearticlesr
dc.rights.licenseARRsr
dcterms.abstractБркљачић, Јелена; Таталовић, Никола; Милер, Марко; Орешчанин-Душић, Зорана; Николић, Милан; Милошевић, Верица; Благојевић, Душко; Спасић, Снежана; Миљевић, Чедо; Видоња Узелац, Теодора; Платановић Aризановић, Лена; Николић-Кокић, Aлександра;
dc.citation.volume84
dc.citation.issue4
dc.citation.spage173
dc.citation.epage182
dc.citation.rankM21~
dc.identifier.pmid33234086
dc.identifier.doi10.1080/15287394.2020.1844827
dc.identifier.scopus2-s2.0-85096601923
dc.identifier.wos000592044000001
dc.type.versionpublishedVersionsr


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