Cytochrome P450 2E1 (CYP2E1) may be a central pathway in generating oxidative stress, nitrosative stress, lipid peroxidation, and causing hepatotoxic injury by various hepatotoxins. CYP2E1 inducers including alcohol and pyrazole could potentiate the hepatotoxicity caused by Jo2 Fas agonist antibody, suggesting that overexpression of CYP2E1 might contribute to the synergy and susceptibility of the liver to Fas-induced injury. Potential mechanisms involved in the potentiated toxicity include elevated oxidative stress, nitrosative stress, lipid peroxidation, apoptosis, decreased level of antioxidants, TNF-α production and the activation of MAP kinase. Clarification of CYP2E1-dependent hepatotoxicity and interactions with other hepatotoxins will lead to a better understanding of the pathogenesis of hepatotoxicity and may help to lead to strategies which protect against the liver injury.
Buy this Article