Exogenous doxorubicinol induces cardiotoxic effects in rats

An investigation was performed in the rat to assess the cardiotoxic effects of exogenous doxorubicinol compared with those induced by an equimolar dose of its parent drug doxorubicin. Rats received synthetic doxorubicinol or doxorubicin 3 mg/kg i.v. weekly for 3 weeks and were observed for a further period of 4 weeks. Survival, body growth, ECG parameters, and heart histopathology were studied. Doxorubicin markedly affected rat body growth, as well as several ECG parameters such as S alpha T, R alpha T, alpha TP and T-wave. Typical cardiac histological alterations were also induced by doxorubicin. In a similar way, doxorubicinol treatment was associated with a significant inhibition of rat body weight increase, and the appearance of ECG alterations as well as both macro- and microscopic signs of cardiac tissue damage. However these effects were delayed in time and their severity was lower compared with doxorubicin. Overall results indicate that doxorubicinol induces a doxorubicin-like toxic syndrome mainly affecting the heart, although to a lower degree of severity than that caused by the parent drug. It is suggested that the lower toxic potential displayed by doxorubicinol might be due at least in part to its greater polarity and a consequently lower cardiac tissue uptake compared with doxorubicin.