Lipid peroxidation, CYP2E1 and arachidonic acid metabolism in alcoholic liver disease in rats

The Journal of Nutrition
Samuel W FrenchE Albano

Abstract

The role of cytochrome P450 metabolism of fatty acids and lipid peroxidation in the alterations of the fatty acid composition of the liver and liver pathology was investigated. The CYP2E1 inhibitors partially prevented CYP2E1 induction by ethanol and completely blocked lipid peroxidation. However, the liver pathology induced by ethanol was only partially prevented as was the decrease in arachidonic acid in total liver lipid, triglycerides and cholesterol esters. This means that liver peroxidation induced by ethanol can not completely account for the liver pathology or the decrease in arachidonic acid caused by ethanol. Lauric acid omega-1 hydroxidation by the liver microsomes in vitro was increased by ethanol and partially blocked by CYP2E1 inhibitors. However, although ethanol feeding increased the total hydroxidation and epoxidation of arachidonic acid, these were not inhibited by CYP2E1 inhibitors. Thus the ethanol-induced arachidonic acid depletion is not likely due to CYP2E1 metabolism of arachidonic acid, since the severity of liver pathology correlated negatively with the decrease in arachidonic acid in the ethanol-fed rats. The increase in its metabolism by microsomes and decrease in synthesis may be an important mechan...Continue Reading

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Citations

Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Jose M Jimenez-Lopez, Arthur I Cederbaum
May 19, 2009·Archives of Toxicology·Arthur I CederbaumDefeng Wu
Jun 4, 2014·Alcoholism, Clinical and Experimental Research·Muna SapkotaMichael L McCaskill
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Dec 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Natalia NietoArthur I Cederbaum
Jun 6, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Leila GobejishviliCraig McClain
Jul 23, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stéphanie MadecAnne Corlu
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Dec 15, 2007·Free Radical Biology & Medicine·Yongke Lu, Arthur I Cederbaum

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