Evaluation of the role of captopril on clozapine-induced cardiotoxicity and hematotoxicity in adult male albino rats

Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to inve...

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Published inToxicology research and application Vol. 1; p. 239784731769653
Main Authors Abdel Hamid, Omaima I, Ahmed, Marwa G, Hassaneine, Hanan MA, Rashed, Hayam E
Format Journal Article
LanguageEnglish
Published London, England SAGE Publications 01.01.2017
Sage Publications Ltd
Subjects
Angiotensin-converting enzyme inhibitors
Antioxidants
Antipsychotics
Biochemical markers
Bone marrow
Calcium-binding protein
Captopril
Cardiotoxicity
Clozapine
Deoxyribonucleic acid
DNA
Enzyme inhibitors
Glutathione
Glutathione peroxidase
Guanosine
Heart diseases
Malondialdehyde
Mental disorders
Myocarditis
Oxidative stress
Peptidyl-dipeptidase A
Peroxidase
Schizophrenia
Troponin
Troponin I
Heart
bone marrow
schizophrenia
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Summary:Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to investigate the protective effect of captopril against CLZ-induced myocarditis, and since both drugs have hematotoxic effects, this study aimed to clarify the effect of their combined use on the bone marrow. The study was conducted for 4 weeks on 50 adult male albino rats divided into five groups: group I (negative control), group II (positive control), group III treated with captopril 5 mg/kg/day, group IV treated with CLZ 25 mg/kg/day, and group V treated with captopril (5 mg/kg) 1 hour before CLZ (25 mg/kg/day). CLZ group showed a significant increase in serum troponin I, marked histopathological changes, and immunohistochemical staining of DNA degradation product 8-hydroxy-2-deoxy guanosine (8-OHdG). It significantly increased malondialdehyde level and decreased glutathione peroxidase. Captopril coadministration decreased the histopathological hallmarks and biochemical marker of myocarditis and attenuated CLZ effects on the oxidative stress parameters and 8-OHdG, suggesting its protective action against CLZ-induced myocarditis. Complete blood count and bone marrow evaluation was normal indicating that captopril, in the protective dose given, didn’t increase the risk of CLZ-induced hematotoxicity
ISSN:2397-8473
2397-8473
DOI:10.1177/2397847317696539