Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
| Autor: | Jelena Nestorov, Marko Miler, Verica Milošević, Ana Mijušković, Nikola Tatalović, Aleksandra Nikolić-Kokić, Duško Blagojević, Čedo Miljević, Milan Nikolić, Mihajlo B. Spasić, Zorana Oreščanin-Dušić, Milica Mijović |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Antioxidant Myocarditis Indoles Health Toxicology and Mutagenesis medicine.medical_treatment SOD1 ziprasidone Pharmacology Toxicology medicine.disease_cause Antioxidants Piperazines Superoxide dismutase 03 medical and health sciences 0302 clinical medicine Sertindole medicine Animals Ziprasidone Rats Wistar Clozapine 030102 biochemistry & molecular biology biology business.industry Myocardium Imidazoles heart morphology Heart medicine.disease 3. Good health Rats Thiazoles biology.protein sertindole business Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress medicine.drug Antipsychotic Agents |
| Zdroj: | Journal of Toxicology and Environmental Health, Part A Journal of Toxicology and Environmental Health. Part A |
| Popis: | 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 4 week 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- α, tumor necrosis factor alpha. |
| Databáze: | OpenAIRE |
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