Protective effect of caffeic acid phenethyl ester on tert-butyl hydroperoxide-induced oxidative hepatotoxicity and DNA damage.

Increased oxidative stress and associated high levels of free radical generation have been described to occur during the pathogeneses of various diseases in animal models. In the present work, we investigated the protective effects of the phenethyl ester of caffeic acid (CAPE), an active component of honeybee propolis, on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in a cultured HepG2 cell line and in rat liver. CAPE was found to significantly reduce t-BHP-induced oxidative injury in HepG2 cells, as determined by cell cytotoxicity, and lipid peroxidation and reactive oxygen species (ROS) levels in a dose-dependent manner. Furthermore, CAPE protected HepG2 cells against t-BHP-induced oxidative DNA damage, as determined by the Comet assay. Consistently, CAPE reduced hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and H2O2, and also removed the superoxide anion generated by a xanthine/xanthine oxidase system. Our in vivo study showed that pretreatment with CAPE prior to the administration of t-BHP significantly and dose-dependently prevented increases in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced lipid peroxidation in rat liver. Moreover, histopathological evaluation of livers consistently revealed that CAPE reduced liver lesion induction by t-BHP. Taken together, these results suggest that the protective effects of CAPE against t-BHP-induced hepatotoxicity may, at least in part, be due to its ability to scavenge ROS and protect DNA from oxidative stress-induced damage.