Cytochrome P450 2E1 (CYP2E1) may be a key pathway in generating oxidative stress

nitrosative stress

lipid peroxidation

and causing alcoholic liver injury by various hepatotoxins. It was found that CYP2E1 induction and liver injury occur with co-administration of ethanol and hepatotoxins. CYP2E1 inducers including alcohol and pyrazole could potentiate the hepatotoxicity caused by FAS antibody or LPS

suggesting that overexpression of CYP2E1 might contribute to the synergy and susceptibility of the liver to FAS/LPS-induced liver injury. Thus

CYP2E1 and its polymorphism have important role in liver injury caused by ethanol and are also associated with nonalcoholic steatohepatitis (NASH). Ethanol ingestion and toxin administration drive more CYP2E1 induction contributing to the more severe liver injury. Potential mechanisms involved in the potentiated toxicity include elevated oxidative stress

nitrosative stress

lipid peroxidation

apoptosis

hypoxia

TNF-α production

decreased level of antioxidants and activation of MAP kinase. Clarification of CYP2E1-dependent liver injury and interactions with other hepatotoxins will lead to a better understanding to the pathogenesis of hepatotoxicity and may help to give strategies which protect the liver from alcoholic liver injury.