A. Podesta et al., EVALUATION OF 4'-IODO-4'-DEOXYDOXORUBICIN-INDUCED CARDIOTOXICITY IN 2EXPERIMENTAL RAT MODELS, Toxicologic pathology, 22(1), 1994, pp. 68-71
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.