In the humanized CYP2E1 knockin mouse [23], some differences were observed compared to the wild type mice expressing mouse CYP2E1 such as rates of p-nitrophenol (but not chlorzoxazone) oxidation and sensitivity to toxicity by acetaminophen. A major goal of the current report was to validate that the decreased fatty liver produced by chronic ethanol feeding in CYP2E1 knockout mice and the decreased ethanol-induced oxidative stress was indeed due to the deficiency in CYP2E1 by evaluating whether such actions by ethanol are restored when CYP2E1 is restored in the knockout mice. Another important goal was to study whether human CYP2E1 could effectively mimic mouse CYP2E1 in contributing to ethanol-induced fatty liver, oxidant stress and liver injury and thus allow assessment of the human CYP2E1 to modulate actions of chronic ethanol administration in a whole animal model system.
