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