The Cardioprotective Effects of an Antiemetic Drug, Tropisetron, on Cardiomyopathy Related to Doxorubicin

Cardiotoxicity is a life-threatening side effect of doxorubicin (DOX). Although the responsible mechanisms are largely unknown, it is demonstrated that DOX induces an elevation in the level of creatine kinase isoenzyme, lactic dehydrogenase, creatine phosphokinase, and troponin T in serum and reduces body/heart weight. In addition, cardiotoxicity is further confirmed by changes in ECG parameters and papillary muscle contractile force. Tropisetron is an effective antiemetic drug for chemotherapy-induced emesis. There is ample evidence that tropisetron exerts immune modulatory and anti-inflammatory properties. The present study was designed to investigate the protective effects of tropisetron pretreatment against DOX-induced cardiotoxicity in rats. In this study, DOX toxicity was induced by a single intraperitoneal injection (15 mg/kg), and in treated group, tropisetron (3 mg/kg; i.p) was administered 1 h prior to DOX injection. Our results indicated that tropisetron potently decreased body/heart weight loss and mortality rate and also improved ECG changes as well as heart contractility. In addition, tropisetron robustly counteracted the increase in the levels of serum biomarkers and alleviated the histopathological changes in rats' hearts as compared with the DOX group. Taken together, these results demonstrate that tropisetron has potent cardioprotective effects against DOX-induced cardiotoxicity.