While some studies support a role for CYP2E1 in the hepatotoxic actions of ethanol [5–9], others do not [10–12].There is concern over the specificity of some of the inhibitors utilized in these studies, e.g. gadolinium chloride may affect levels of cytochrome P450 enzymes such as CYP2E1 beyond inactivation of Kuppfer cells [13,14] or diallyl sulfide may increase levels of antioxidants such as heme-oxygenase-1 besides inhibiting CYP2E1 [15]. Bradford et al [16] reported that CYP2E1 but not NADPH oxidase was required for ethanol-induced oxidative DNA damage in rodent liver and may play a key role in ethanol-associated hepatocarcinogenesis, whereas NADPH oxidase but not CYP2E1 played the major role in ethanol-induced hepatotoxicity. Why CYP2E1 may be important for one mode of liver injury, DNA damage, but not necrosis and pathological changes is not clear. Additional study is needed in assessing the role of CYP2E1 in the actions of ethanol.
