There are many possible pathways and mechanisms by which chronic ethanol feeding can elevate oxidant stress, and induction of CYP2E1 is one of these [27]. Lipid peroxidation, as assayed by formation of thiobarbituric acid-reactive substances (TBARs) in the liver, was increased 2-fold by ethanol in WT mice and 3-fold in KI mice (Fig. 4A). No increase by ethanol was found in livers from the KO mice. GSH levels were lowered about 50% by ethanol in livers from WT mice and about 70% in livers from the KI mice (Fig. 4B).. Ethanol had no effect on GSH levels in livers from KO mice. Formation of 3-nitrotyrosine protein adducts is one assay for detection of peroxynitrite formation [28]. Low levels of 3-NT staining were observed in livers from the ethanol-fed WT and KO mice, but a more intense staining was observed in livers from the ethanol-fed KI mice (Fig. 4C). 4- HNE protein adducts as detected by immunohistochemistry were elevated in WT mice and to a greater extent in KI mice as compared to dextrose controls(4D). Ethanol did not elevate 4-HNE adducts
