RT Journal Article
SR Electronic
T1 The Effects of Ethanol and Acetaldehyde on the Metabolism of Prostaglandin E<sub>2</sub> and Leukotriene B<sub>4</sub> in Isolated Rat Hepatocytes
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 155
OP 161
VO 285
IS 1
A1 Hankin, Joseph A.
A1 Clay, Carl E.
A1 Murphy, Robert C.
YR 1998
UL http://jpet.aspetjournals.org/content/285/1/155.abstract
AB The effects of ethanol and acetaldehyde on the metabolism of leukotriene B4 (LTB4) and PGE2 were investigated in isolated cultures of rat hepatocytes. LTB4undergoes initial cytochrome P450-dependent ω-oxidation leading to the principal metabolites 20-hydroxy-LTB4, 20-carboxy-LTB4 and the ω/β-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, β-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 β-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 metabolic distribution, with a corresponding decrease in concentration of tetranor-PGE1. The amount of dinor-PGE2 that was produced remained relatively unchanged in response to increasing concentrations of ethanol. Acetaldehyde concentrations from 0.1 mM to 1 mM did not affect metabolite distribution or the overall magnitude of PGE2metabolism. Concentrations of acetaldehyde higher than 1 mM decreased all β-oxidation metabolites. Ethanol, at physiologically relevant concentrations, could alter eicosanoid metabolism in the liver by inhibiting LTB4 metabolism and altering that of PGE2. The American Society for Pharmacology and Experimental Therapeutics