CLOZAPINE-INDUCED MYOCARDITIS IN RATS: ROLE OF L-CARNITINE IN PROTECTION

Clozapine (CLZ) is an atypical antipsychotic and often used in refractory schizophrenia. The present study was carried out to investigate clozapine-induced myocarditis in albio rats and evaluate if L-Carnitine can reduce myocarditis through cardio-protective effect. The rats were divided into four groups as follows; group 1: negative control; group 2: received. 25 mg/kg/day/4 weeks of CLZ intraperitoneal (I.P), group 3: received 500 mg/kg/day/4 weeks of L-Carnitine I.P and, group 4: received 25 mg/kg/day/4 weeks of CLZ I.P plus 500 mg/kg/day L-Carnitine I.P. The rats were sacrificed on the 29th day of the experiment. Measuring serum levels of lactate dehydrogenase (LDH) enzyme, creatine phosphokinase (CPK-MB), tissue malondialdehyde (MDA), and glutathione peroxidase (GSHPx) was done. Histopathological examination of heart was performed by light and electron microscopy. The current study revealed significant statistical elevation of serum cardiac enzymes; LDH and CPK-MB in CLZ-treated group in comparison to control and significant reduction of cardiac enzymes in rats co-treated with CLZ & LCarnitine in comparison to CLZ-treated group. Significant statistical increase was observed in tissue MDA with significant reduction in tissue GSHPx in CLZ-treated group as compared to control group. Meanwhile, significant reduction in tissue MDA with significant increase in tissue GSHPx in rats co-treated with CLZ & L-Carnitine in comparison to CLZ-treated group. Histopathological changes in CLZ-treated group were showed by light microscopy and by electron microscopy. In group co-treated with CLZ & L-Carnitine, the histopathological changes were disappeared. Conclusion is that CLZ induced evident myocarditis which was partially relieved by L-Carnitine. So, L-Carnitine had cardio-protective effects in CLZ-induced myocarditis in rats