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Chunk #18 — 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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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 in the KO mice. In situ detection of ROS using the superoxide sensitive probe DHE showed that ethanol elevated DHE fluorescence in WT and to a greater extent in KI mice but not in the KO mice (Fig 4E). Thus, levels of oxidant stress induced by ethanol appeared to follow a similar pattern of induction of CYP2E1 by ethanol, being highest in the CYP2E1 KI mice, intermediate in the WT mice, and lowest in the CYP2E1 KO mice.