Recently, we found that ethanol induction of CYP2A5 was CYP2E1-dependent (9, 12). It is well known that ethanol can induce CYP2E1, and that CYP2E1-mediated oxidative stress is a risk factor for alcoholic liver injury (10, 11). Indeed, ethanol-induced fatty liver, an early stage of alcoholic liver injury, was observed in WT mice but not in cyp2e1−/− mice (17); when human CYP2E1 was reintroduced and expressed in cyp2e1−/− mice, the alcoholic liver injury was observed again (23). We initially hypothesized that CYP2A5 is a downstream molecule of CYP2E1 signalling that promotes alcohol-induced oxidative stress and liver injury. However, in this study we found that CYP2A5 plays an antioxidant role, i.e. CYP2A5 protects against alcoholic liver injury and does not promote it.
