not induce HO-1 in rodents (29). In the present study, a similar decrease in GSH levels was observed in ethanol-treated WT mice and cyp2a5−/− mice; thus, other Nrf2-regulated mechanisms may be involved. CYP2A6, the human orthologue to CYP2A5, is regulated by Nrf2 (7, 30). Recently, we found that the ethanol induction of CYP2A5 occurs through a CYP2E1-ROS-Nrf2 pathway. Nrf2 appears to play a central role in the ethanol induction of CYP2A5 as the increase in CYP2A5 was less in Nrf2−/− mice than WT mice, but the increase in CYP2E1 was comparable in Nrf2−/− and WT mice (12). Whether cyp2a5 is among the panel of Nrf2-regulated antioxidant genes is a very interesting issue that needs further studies. Alcoholic liver diseases include a spectrum of disorders ranging from steatosis (fatty liver) to steatohepatitis (inflammation), liver fibrosis, cirrhosis, and even liver cancer. In patients with alcoholic and non-alcoholic fatty liver, hepatic CYP2A6 was up-regulated and, very interestingly, liver CYP2A6 expression co-localized with lipid droplets (8). These results suggest that human CYP2A6 may participate in the regulation of lipid metabolism for the development of both alcoholic and non-alcoholic fatty liver. Kirby et al first proposed the notion that CYP2A5 may involve hepatic lipid metabolism
