PMID: 9536005May 16, 1998Paper

The effects of ethanol and acetaldehyde on the metabolism of prostaglandin E2 and leukotriene B4 in isolated rat hepatocytes

The Journal of Pharmacology and Experimental Therapeutics
J A HankinRobert C Murphy

Abstract

The effects of ethanol and acetaldehyde on the metabolism of leukotriene B4 (LTB4) and PGE2 were investigated in isolated cultures of rat hepatocytes. LTB4 undergoes initial cytochrome P450-dependent omega-oxidation leading to the principal metabolites 20-hydroxy-LTB4, 20-carboxy-LTB4 and the omega/beta-oxidation product 18-carboxy-LTB4. The addition of low concentrations of ethanol (25 mM) dramatically changes the relative amounts of these metabolite products by inhibiting the alcohol dehydrogenase-mediated oxidation of 20-hydroxy-LTB4. Addition of acetaldehyde to the incubation, up to 1 mM, had no significant effect on overall metabolism or distribution of metabolites. Above 1 mM acetaldehyde, beta-oxidation of LTB4 was inhibited. Thus the effect of ethanol on the metabolism of LTB4 appears to be due to ethanol itself and not to secondary effects from the metabolic transformation of ethanol to acetaldehyde in the cells. PGE2 is metabolized in isolated rat hepatocytes to produce chain-shortened products of beta-oxidation characterized as dinor-PGE1, dinor-PGE2, tetranor-PGE1, tauro-dinor-PGE1 and tauro-dinor-PGE2. Low concentrations of ethanol (25 mM) were found to increase the relative concentration of dinor-PGE1 in the metab...Continue Reading

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