Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats?
Clozapine is an atypical antipsychotic drug selectively effective in the treatment of refractory schizophrenia. However, myocarditis, as a serious cardiotoxic effect, has in several case reports been associated with clozapine therapy. Ani increase in the free radical production and ischemia, probabl...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2014-09-01
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| Series: | Egyptian Journal of Forensic Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090536X14000227 |
| _version_ | 1811239696450191360 |
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| author | Basel A. Abdel-Wahab Metwally E. Abdalla Mohamed M. El-khawanki |
| author_facet | Basel A. Abdel-Wahab Metwally E. Abdalla Mohamed M. El-khawanki |
| author_sort | Basel A. Abdel-Wahab |
| collection | DOAJ |
| description | Clozapine is an atypical antipsychotic drug selectively effective in the treatment of refractory schizophrenia. However, myocarditis, as a serious cardiotoxic effect, has in several case reports been associated with clozapine therapy. Ani increase in the free radical production and ischemia, probably induced by clozapine-induced release of catecholamines, have been hypothesized to trigger an inflammatory response that leads to the clinically observed cardiomyopathy and sudden death even in young patients. The aim of this work is to study the role of oxidative stress in clozapine-induced myocarditis and myocardial DNA damage in a rat model.
Methods: Male Wistar rats, age ∼6 weeks, were administered 5, 10 or 25 mg/kg clozapine daily for 21 days; saline-treated rats served as the control. Heart sections were stained with hematoxylin and eosin for histopathological examination. Plasma CK-MB, LDH and TNF-α concentrations were determined. Myocardial oxidative stress (MDA and NO), antioxidant (GSH and GSH-Px) parameters, and the marker of oxidative DNA damage (8-OHdG) were determined.
Results: Clozapine treatment resulted in significant dose-related increases in myocardial inflammation with increased plasma TNF-α, CK-MB and LDH levels. Myocardial MDA, NO and serum and cardiac 8-OHdG levels increased while GSH level and GSH-Px activity decreased with the highest significance seen with the largest tested dose (25 mg/kg) of clozapine.
Conclusions: Clozapine, in relatively large doses induced myocarditis consistently with increased myocardial oxidative stress, DNA damage and inflammatory cytokines in rat a model. |
| first_indexed | 2024-04-12T13:05:39Z |
| format | Article |
| id | doaj.art-2ebc40da2f2b4273860bc4e5eaf0e27b |
| institution | Directory Open Access Journal |
| issn | 2090-536X |
| language | English |
| last_indexed | 2024-04-12T13:05:39Z |
| publishDate | 2014-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Forensic Sciences |
| spelling | doaj.art-2ebc40da2f2b4273860bc4e5eaf0e27b2022-12-22T03:32:02ZengSpringerOpenEgyptian Journal of Forensic Sciences2090-536X2014-09-0143758210.1016/j.ejfs.2014.04.001Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats?Basel A. Abdel-Wahab0Metwally E. Abdalla1Mohamed M. El-khawanki2Department of Pharmacology, College of Medicine, Assiut University, Assiut, EgyptDepartment of Forensic Medicine and Toxicology, College of Medicine, Suez Canal University, Ismailia, EgyptDepartment of Clinical Pathology, College of Medicine, Najran University, Najran, Saudi ArabiaClozapine is an atypical antipsychotic drug selectively effective in the treatment of refractory schizophrenia. However, myocarditis, as a serious cardiotoxic effect, has in several case reports been associated with clozapine therapy. Ani increase in the free radical production and ischemia, probably induced by clozapine-induced release of catecholamines, have been hypothesized to trigger an inflammatory response that leads to the clinically observed cardiomyopathy and sudden death even in young patients. The aim of this work is to study the role of oxidative stress in clozapine-induced myocarditis and myocardial DNA damage in a rat model. Methods: Male Wistar rats, age ∼6 weeks, were administered 5, 10 or 25 mg/kg clozapine daily for 21 days; saline-treated rats served as the control. Heart sections were stained with hematoxylin and eosin for histopathological examination. Plasma CK-MB, LDH and TNF-α concentrations were determined. Myocardial oxidative stress (MDA and NO), antioxidant (GSH and GSH-Px) parameters, and the marker of oxidative DNA damage (8-OHdG) were determined. Results: Clozapine treatment resulted in significant dose-related increases in myocardial inflammation with increased plasma TNF-α, CK-MB and LDH levels. Myocardial MDA, NO and serum and cardiac 8-OHdG levels increased while GSH level and GSH-Px activity decreased with the highest significance seen with the largest tested dose (25 mg/kg) of clozapine. Conclusions: Clozapine, in relatively large doses induced myocarditis consistently with increased myocardial oxidative stress, DNA damage and inflammatory cytokines in rat a model.http://www.sciencedirect.com/science/article/pii/S2090536X14000227ClozapineMyocarditisOxidative stressTNF-αDNA damage |
| spellingShingle | Basel A. Abdel-Wahab Metwally E. Abdalla Mohamed M. El-khawanki Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? Egyptian Journal of Forensic Sciences Clozapine Myocarditis Oxidative stress TNF-α DNA damage |
| title | Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? |
| title_full | Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? |
| title_fullStr | Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? |
| title_full_unstemmed | Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? |
| title_short | Does clozapine induce myocarditis, myocardial oxidative stress and DNA damage in rats? |
| title_sort | does clozapine induce myocarditis myocardial oxidative stress and dna damage in rats |
| topic | Clozapine Myocarditis Oxidative stress TNF-α DNA damage |
| url | http://www.sciencedirect.com/science/article/pii/S2090536X14000227 |
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