Associated with the fatty liver induced by ethanol was an increase in oxidative/nitrosative stress as reflected by the increase in TBARS, 3-NT and 4-HNE staining, and DHE fluorescence and the decrease in GSH levels in the WT mice fed ethanol. CYP2E1 is suggested be a major contributor to ethanol-induced oxidant stress. Results in Fig. 4 show that ethanol caused oxidative stress in WT mice, but the ethanol-induced oxidative stress was decreased in CYP2E1 KO mice. It is the absence of CYP2E1 in the CYP2E1 KO mice that plays a major role in blunting of the ethanol-induced oxidant stress since restoring CYP2E1 restores oxidative/nitrosative stress. As discussed above for fatty liver, human CYP2E1 was the CYP2E1 which restores the oxidative/nitrosative stress indicating that human CYP2E1 can potentiate development of oxidative/nitrosative stress in an oral model of chronic ethanol administration, and that results on oxidative/nitrosative stress extrapolated from rodent models of ethanol intake can be extrapolated to human models of ethanol intake.
