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

Samuel W. French, Michio Morimoto, Ronald C. Reitz, Dennis Koop, Bethany Klopfenstein, Karen Estes, Paolo Clot, Magnus Ingelman-Sundberg, Emanuel Albano

Research output: Contribution to journalArticle

79 Scopus citations

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 ω-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 mechanism of ethanol-induced liver injury.

Original languageEnglish (US)
Pages (from-to)907S-911S
JournalJournal of Nutrition
Volume127
Issue number5 SUPPL.
DOIs
StatePublished - 1997

Keywords

  • cholesterol
  • cytochrome P450
  • ethanol
  • fatty acids
  • rats

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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    French, S. W., Morimoto, M., Reitz, R. C., Koop, D., Klopfenstein, B., Estes, K., Clot, P., Ingelman-Sundberg, M., & Albano, E. (1997). Lipid peroxidation, CYP2E1 and arachidonic acid metabolism in alcoholic liver disease in rats. Journal of Nutrition, 127(5 SUPPL.), 907S-911S. https://doi.org/10.1093/jn/127.5.907s