General and cardiac toxicity of adriamycinol in rats

The toxic effects of adriamycinol, the main metabolite of adriamycin, were studied during repeated treatment in rats, by evaluating survival, body growth, electrocardiographic parameters and cardiac histopathology. Different groups of animals were treated with 3 mg/kg weekly of adriamycinol or adriamycin for the first 3 weeks of the experiment and were observed for a further period of 4 weeks. One adriamycinol-treated rat and two adriamycin-treated ones died during the experiment. Adriamycinol inhibited rat body weight increase and induced the appearance of ECG alterations (especially S alpha T widening) as well as moderate histological cardiac lesions, but to a lesser extent and severity compared with adriamycin, which, in turn, markedly affected rat body growth, ECG parameters (especially the S alpha T segment and the T-wave) and the histological cardiac picture. The data of the present study indicate that adriamycinol induces an adriamycin-like toxic syndrome mainly affecting the heart, although to a lesser degree of severity than the parent drug. The lower toxic potential displayed by the metabolite might be due to its greater polarity compared with adriamycin, which implies a lower uptake of adriamycinol into tissues, especially the heart.