CYP2E1 is an active generator of ROS, and CYP2E1-mediated oxidative stress contributes to liver injury (10). We thus wondered whether CYP2E1-dependent induction of CYP2A5 has an effect on CYP2E1-mediated oxidative stress. GSH was comparably decreased by ethanol feeding in cyp2a5−/− and cyp2a5+/+ mice (Fig 4A). However, after ethanol feeding, more 3-NT adduct formation was detected in cyp2a5−/− mice than cyp2a5+/+ mice (Fig 4B). Similarly, more 4-HNE adducts were formed in cyp2a5−/− mice than cyp2a5+/+ mice (Fig 4C). Furthermore, TBARS, a marker of lipid peroxidation, was increased by ethanol feeding more than 2-fold in cyp2a5−/− mice, but only by 50% in cyp2a5+/+ mice (Fig 4D). These results suggest that CYP2A5 induction inhibits alcohol-induced oxidative stress.
