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Chunk #19 — Results — Ethanol-Induced Oxidant Stress

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Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in mice.
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Levels of some antioxidant enzymes were assayed by immunoblot analysis. Ethanol had little or no effect on the levels of catalase, thioredoxin (Trx), SOD-1 or SOD-2 in any group (data not shown). Ethanol lowered the levels of GPx-4 55%, 58% and 39% in the WT, KO and KI mice, respectively as compared to their appropriate dextrose-fed control (data not shown). This decline in GPx-4 levels by ethanol, unlike the 5 parameters of oxidant stress discussed above (increase in TBARs, decrease in GSH, increase in 3-NT and 4-HNE staining, increase in DHE fluorescence) appears to be independent of CYP2E1 since a comparable decline was found in CYP2E1 KO mice as with the WT mice.