EVALUATION OF 4'-IODO-4'-DEOXYDOXORUBICIN-INDUCED CARDIOTOXICITY IN 2EXPERIMENTAL RAT MODELS

In the present study, 1 single-dose and 1 multiple-dose models were ap plied in studying 4'-iodo-4'-deoxydoxorubicin (I-DX) cardiotoxicity. A nthracycline cardiotoxicity has been reproduced in several animals inc luding mice, rats, hamsters, rabbits, dogs, and monkeys. Of these spec ies, the rat can be considered the most suitable species for the study of anthracycline-induced cardiomyopathy. The cardiotoxicity induced b y 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 gi ven single or repeated doses of the compounds, injected intravenously in a volume of 5.0 ml/kg. Animals were observed for up to 35 wk to fol low the progression of the lesions. Cardiomyopathy was evaluated throu gh well-established qualitative/quantitative morphological grading. Th e new DX derivative proved to be clearly less cardiotoxic than DX with both treatment schedules. Although both models can be considered usef ul for evaluating and comparing the cardiotoxicity of new anthracyclin e 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 un detected in the single-dose test.