Cardiotoxicity and Hepatotoxicity Induced by Clozapine in Adult Male Albino Rats and Possible Protection by Selenium: A Histological Study

Abstract

Background: Clozapine is an efficacious antipsychotic drug particularly in schizophrenic patients refractory to other agents. Treatment with clozapine was reported to be associated with sudden death, myocarditis and hepatotoxicity in some patients. Aim of the Work: This study was conducted to investigate the toxic effect of clozapine on cardiac muscle and liver of adult male albino rats and to assess the potential protective role of selenium. Materials and Methods: This study employed fifty adult male albino rats randomly divided into five equal groups. Group I: Control group, Group II received daily 1 ml of 0.1 M HCl, balanced in phosphate buffered saline intraperitoneally (i.p.), Group III received oral selenium (1.5 mg/kg), Group IV received Clozapine (25 mg/kg) i.p. daily and Group V received both clozapine and selenium. After 14 days, the liver and ventricular myocardium of each animal were dissected and processed for light and electron microscopic studies. Results: After clozapine administration, the ventricular myocardium showed fragmentation and separation of cardiac muscles with diffuse mixed inflammatory cellular infiltrate. The Z-lines were irregularly oriented with rupture of mitochondrial membranes and cristae. The liver exhibited extensive inflammatory cellular infiltration around the portal areas and vacuolated hepatocyte cytoplasm with rupture of membranes and cristae of some mitochondria. Concomitant administration of selenium with clozapine displayed an observable protection against these changes. Conclusion: Selenium may have a protective role against cardiotoxicity and hepatotoxicity induced by clozapine therapy