A NEW ANTITHROMBOTIC AGENT, ASPALATONE, ATTENUATED CARDIOTOXICITY INDUCED BY DOXORUBICIN IN THE MOUSE - POSSIBLE INVOLVEMENT OF ANTIOXIDANTMECHANISM

A new antithrombotic agent, aspalatone (APT; acetyl salicylic acid mal tol ester), was synthesized by esterification of acetyl salicylic acid (ASP) and maltol (MAL). It was suggested that APT possessed an antiox idant effect in in vitro. To evaluate the putative antioxidant effect of APT in in vivo, we developed doxorubicin (DOX)-related cardiac dama ge, which might be implicated by oxidative stress. Vitamin E (Vit E) w as included in the present study as an example of an antioxidant. Prol onged treatments with APT, MAL and Vit E significantly reduced the mor tality in animals receiving multiple dose of DOX (3 mg/kg x 4). The po tential role of APT, MAL and Vit E against DOX insult may be explained by the induction of glutathione peroxidase activity accompanied by th e inhibition of lipid peroxidation. Prolonged treatments of APT, MAL a nd Vit E also ablated histopathological evidence of DOX cardiomyopathy . ASP challenge, however, did not affect the mortality, myocardial les ion and antioxidant deficit induced by DOX treatments. In conclusion, the protective effect of APT was equipotent to that of Vit E against D OX cardiotoxicity. The results also suggest that the antiperoxidative effect of APT plays a protective role in DOX-related cardiotoxic side effect.