The Rat Model in the Comparative Evaluation of Anthracyclines Cardiotoxicity

In the present investigation, the cardiotoxic effects of three anthracycline analogs (doxorubicin, 4′-epi-doxorubicin and 4′-deoxy-doxorubicin) were compared. For this purpose, 9.0 mg/kg of doxorubicin, divided into three closely spaced sub-doses, were injected intravenously in rats. The two derivatives were administered according to the same time schedule and their doses were chosen on the basis of the clinically adopted ratio, doxorubicin : 4′-epidoxorubicin : 4′-deoxy-doxorubicin = 1:1: 0.5. The degree of cardiomyopathy induced by the three anthracyclines was evaluated by ECG changes and morphological alterations. Doxorubicin was found to produce a significant degree of cardiotoxicity, thus confirming the validity of the experimental model adopted. Both 4′-substituted derivatives proved to be less cardiotoxic than the parent compound, although not completely devoid of this side effect.