Therapeutic action of ashwagandha extract on apoptosis and cell proliferation in the heart of rat fetuses prenatally treated with clozapine

Abstract

ABSTRACT An effective atypical antipsychotic medication for treating psychosis is clozapine, especially for patients who have failed to respond to other treatments. However, clozapine-induced cardiotoxicity has generated safety concerns as it may result in sudden mortality. In addition, there is relatively little information on the safety of clozapine during pregnancy. According to several earlier studies, Withania somnifera (ashwagandha) extract has a cardioprotective effect. Therefore, this study aimed to investigate the therapeutic potential of ashwagandha root extract on clozapine-induced cardiotoxicity in rat fetuses. Pregnant rats were administered clozapine (40 mg/kg bw) and/or ashwagandha extract (300 mg/kg bw.) from the sixth to fifteenth day of gestation. Clozapine-induced oxidative stress in developing hearts by decreasing superoxide dismutase and catalase activities and increasing the concentration of cardiac malondialdehyde. Moreover, there was a significant increase in the percentage of apoptotic cells and a decrease in the proliferative capacity of cardiomyocytes. Evidently, clozapine triggered severe pathological changes in fetal cardiac tissue. In conclusion, ashwagandha root extract can be used to improve the heart oxidative stress, apoptotic and proliferation rates and histopathological changes induced by clozapine in rat fetuses during gestation.