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Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction
- Source :
- Journal of Toxicology and Environmental Health, Part A, Journal of Toxicology and Environmental Health. Part A, Journal of Toxicology and Environmental Health. Part AJ Toxicol Environ Health A
- Publication Year :
- 2020
- Publisher :
- Informa UK Limited, 2020.
-
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.
- Subjects :
- Male
Indoles
medicine.drug_class
Health, Toxicology and Mutagenesis
medicine.medical_treatment
ziprasidone
Glutathione reductase
Atypical antipsychotic
antioxidative enzymes
Pharmacology
liver
Toxicology
Antioxidants
Piperazines
Superoxide dismutase
03 medical and health sciences
0302 clinical medicine
Sertindole
medicine
Animals
Ziprasidone
Rats, Wistar
Antipsychotic
Clozapine
chemistry.chemical_classification
biology
business.industry
Liver Diseases
Glutathione peroxidase
Imidazoles
Rats
3. Good health
030227 psychiatry
Thiazoles
Liver
chemistry
biology.protein
sertindole
business
030217 neurology & neurosurgery
Antipsychotic Agents
medicine.drug
Subjects
Details
- ISSN :
- 10872620 and 15287394
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Journal of Toxicology and Environmental Health, Part A
- Accession number :
- edsair.doi.dedup.....1908906b161a4fa6edf620c2e3a45e82