experiments evaluating the effects of antioxidants on the ethanol-induced liver injury in KI mice. Although other models of hepatotoxicity produced by overexpression of CYP2E1 have been reported e.g. a transgenic model of CYP2E1 overexpression [18,19], or administration of an adenovirus expressing CYP2E1 to mice [66], the advantage of the CYP2E1 KI model is that the actions of the human CYP2E1 can be studied in the total absence of the mouse CYP2E1 thus allowing assessment of the role of human CYP2E1 in ethanol-induced oxidative stress and liver injury. Another point to consider is that the ethanol-induced liver toxicity observed in the intragastric infusion model of ethanol administration is typically associated with endotoxemia and activation of Kupffer cells with the subsequent production of TNF-α [67–70]. Alcohol-induced liver injury in this model is deceased when gram negative bacteria are deleted from the gut by treatment with lactobacillus or antibiotics [71] or when anti-TNF-α antibodies are administered [72] or when TNF-α receptor 1 knockout mice were treated with ethanol [73]. We did not observe any elevation of TNF-α in livers of any of the ethanol-treated mice (Fig. 1), therefore the liver injury in the ethanol-fed KI mice is not associated with an elevation of
