Evaluation of 4′-Iodo-4′-Deoxydoxorubicin-Induced Cardiotoxicity in Two Experimental Rat Models

In the present study, 1 single-dose and 1 multiple-dose models were applied in studying 4'-iodo-4'-deoxydoxorubicin (I-DX) cardiotoxicity. Anthracycline cardiotoxicity has been reproduced in several animals including mice, rats, hamsters, rabbits, dogs, and monkeys. Of these species the rat can be considered the most suitable species for the study of anthracycline-induced cardiomyopathy. The cardiotoxicity induced by I-DX in male Sprague-Dawley rats was compared to that of doxorubicin (DX), used as standard positive control. Groups of 36-42 rats were observed for up to 35 wk to follow the progression of the lesions. Cardiomyopathy was evaluated through well-established qualitative/quantitative morphological grading. The new DX derivative proved to be clearly less cardiotoxic than DX with both treatment schedules. Although both models can be considered useful for evaluating and comparing the cardiotoxicity of new anthracycline derivatives and mimicking the transvenous endomyocardial biopsies in humans, the chronic test seems to be more suitable for compounds like I-DX, which possess a low cardiotoxic potential and which could go undetected in the single-dose test.