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- W2183680865 abstract "In this review, we discuss studies on the role of CYP2E1 in alcohol-induced oxidative stress and how MAPK signaling cascades are involved in alcohol induced liver injury and fat accumulation. Many pathways have been suggested to play a role in how alcohol induces oxidative stress. Considerable attention has been given to alcohol elevated production of lipopolysaccharide (LPS) and TNFα and to alcohol induction of CYP2E1. These two pathways are not exclusive of each other, however, associations and interactions between them, especially in vivo, have not been extensively evaluated. We review our results that increased oxidative stress from induction of CYP2E1 in vivo sensitizes hepatocytes to LPS and TNFα toxicity and that oxidative stress, activation of p38 and JNK MAP kinases, induction of the inducible nitric oxide synthase and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNFα potentiated hepatotoxicity. Binge alcohol drinking induces liver steatosis. The mechanism of acute alcohol induced steatosis and the role of CYP2E1 and MAPK is not clear. Increasing oxidative stress by alcohol can activate the JNK MAP kinase signaling pathway, and JNK might be a target for prevention of alcohol induced steatosis. In wild type (WT) mice, acute alcohol activated CYP2E1, produced fatty liver and increased oxidative stress, which increased activation of the JNK signaling pathway. Acute alcohol-induced fatty liver, JNK activation and oxidative stress were blunted in CYP2E1 knockout mice. The fatty liver, elevated oxidative stress and JNK activation in WT mice were prevented by a JNK inhibitor and by the antioxidant N-acetylcysteine. Thus, mechanistically, acute alcohol elevation of CYP2E1, oxidative stress and activation of JNK interact to cause fatty liver and liver toxicity." @default.
- W2183680865 created "2016-06-24" @default.
- W2183680865 creator A5039170596 @default.
- W2183680865 creator A5046167919 @default.
- W2183680865 creator A5078976123 @default.
- W2183680865 date "2014-01-01" @default.
- W2183680865 modified "2023-09-24" @default.
- W2183680865 title "CYP2E1, oxidative stress and MAPK signaling pathways in alcohol-induced hepatotoxicity" @default.
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