Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology Research Center, Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cardiovasc Toxicol. 2012 Dec;12(4):318-25. doi: 10.1007/s12012-012-9175-x.
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.
心脏毒性是多柔比星（DOX）的一种危及生命的副作用。尽管其负责的机制在很大程度上尚不清楚，但已证明 DOX 会导致血清中肌酸激酶同工酶、乳酸脱氢酶、肌酸磷酸激酶和肌钙蛋白 T 水平升高，并降低体重/心脏重量。此外，心电图参数和乳头肌收缩力的变化进一步证实了心脏毒性。曲昔派特是一种用于化疗引起的呕吐的有效止吐药物。有充分的证据表明曲昔派特具有免疫调节和抗炎作用。本研究旨在探讨曲昔派特预处理对大鼠多柔比星诱导的心脏毒性的保护作用。在这项研究中，通过单次腹腔注射（15mg/kg）诱导 DOX 毒性，在治疗组中，曲昔派特（3mg/kg；腹腔注射）在 DOX 注射前 1 小时给药。我们的结果表明，曲昔派特可有效降低体重/心脏重量减轻和死亡率，并改善心电图变化以及心脏收缩力。此外，与 DOX 组相比，曲昔派特可显著抑制血清生物标志物水平的升高，并减轻大鼠心脏的组织病理学变化。综上所述，这些结果表明曲昔派特对多柔比星诱导的心脏毒性具有强大的心脏保护作用。
