Effect of trimetazidine on early and delayed doxorubicin myocardial toxicity

The influence of the administration of trimetazidine on the myocardial toxicity induced by doxorubicin was studied on an in vivo model in the rat. Trimetazidine was chosen due to its ability to act as a scavenger of oxygen-derived free radicals, which have been implicated in both early and delayed cardiotoxic manifestations after doxorubicin treatment. In the present study, doxorubicin was administered as 4 weekly i.v. injections of 3 mg/kg. The cardiotoxic effects were evaluated by measuring predictive ECG parameters (QT and ST intervals) as well as the contractile performance of atria isolated from treated animals. Heart preparations were also examined by light microscopy. Trimetazidine, 2.5 mg/kg/day i.p. for 3 days before doxorubicin administration plus 2.5 mg/kg/day p.o. for 10 weeks, was unable to prevent the development of doxorubicin-induced long-term cardiotoxicity. However, a significant improvement of the early cardiotoxic signs was observed in trimetazidine-treated rats, as reported in previous investigations. The present findings suggest that different target structures may be involved in the early and delayed free radical-mediated effects of doxorubicin.