CYP2A6 expression was induced by ethanol in human monocytes (7) and, consistently, CYP2A6 up-regulation was observed in livers of alcoholic patients (8). Recently, we found that CYP2A5 expression, along with cyp2a5 mRNA and COH activity, was induced by ethanol feeding in mice and, very interestingly, that ethanol induction of CYP2A5 was CYP2E1-dependent (9). It has long been known that alcohol consumption induces CYP2E1, and CYP2E1 plays an important role in ethanol-induced oxidative liver injury (10, 11). It is possible that CYP2A5 may act as a downstream molecule of the CYP2E1 signalling pathway to promote alcohol-induced liver injury. On the other hand, ethanol induction of CYP2A5 is also regulated by the redox-sensitive transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2) (12). Nrf2 signalling usually protects against oxidative injury by regulating a panel of antioxidant genes (13). Indeed, Nrf2 protects against alcohol-induced liver injury in mice (14). However, one of the remaining questions is: does Nrf2-regulated CYP2A5 act as an antioxidant to protect against alcoholic liver injury? In this study, we investigated the role of CYP2A5 in ethanol-induced liver injury.
