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CYP2E1 catalyzes the oxidation of APAP to NAPQI, a highly reactive metabolite inducing severe massive hepatocellular necrosis ( CYP2E1 knockout mice showed resistance to the APAP high dose-associated hepatotoxicity, suggesting that CYP2E1 is the major cytochrome P450 enzyme participating in APAP metabolism and toxicity ( CYP2E1 in APAP toxicity, CYP enzymes, notably CYP2E1 , generate ROS and lipid peroxidation (Veith and Moorthy, 2018)