Influence of fibrates on ethanol metabolism in rats.
The fibrates are widely used for the reduction of high triglyceride levels. The fibrates act as the peroxisome proliferator-activated receptor alpha ligands to regulate the transcription of large number of genes that affect lipoprotein and fatty acid metabolism. The male rats of Wistar strain, simfibrate-treated (100 mg/kg, 200 mg/kg) or clinofibrate-treated (50 mg/kg, 100 mg/kg), were given ethanol (2 g/kg) orally. Blood ethanol levels on the simfibrate groups (100 mg/kg, 200 mg/kg) were significantly lower than the control groups (p < 0.01). The clinofibrate groups (100 mg/kg) were also lower than the controls (p < 0.05). The fatty acid beta-oxidation activity of liver peroxisome in simfibrate-treated (200 mg/kg) or clinofibrate-treated (100 mg/kg) rats for single administration (2.5 hours before the measurement) and twice administrations (20 and 1 hours before the measurement) were assayed. The activity ratio was 168% in simfibrate (p < 0.05), 146% in clinofibrate in single administration, and 388% in simfibrate (p < 0.01), 200% in clinofibrate (p < 0.01) in twice administrations. Alcohol dehydrogenase of cytosol and aldehyde dehydrogenase of cytosol, microsome and mitochondria in the liver were not induced by these fibrates. These results were suggested that simfibrate and clinofibrate induced beta-oxidation by peroxisome and increased H2O2 production, which led to augmented ethanol metabolism by catalase.
Hayashi
K
K
Department of Legal Medicine, Graduate School of Medicine, Kyorin University, Shinkawa 6-20-2, Mitaka-City, Tokyo 181-8611, Japan.
D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D020675:Peroxisomes / Q000378:metabolism; D010642:Phenoxyacetates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000960:Hypolipidemic Agents; D010642:Phenoxyacetates; C006231:clinofibrate; D000431:Ethanol; D006861:Hydrogen Peroxide; D002994:Clofibrate; C003278:simfibrate