Effects of bezafibrate on ethanol oxidation in rats.
Bezafibrate is used to lower serum lipid levels in humans. Fibrate derivatives induce an enzyme participating in the beta-oxidation by peroxisomes. We gave ethanol (2 g/kg) orally to bezafibrate-treated (300 mg/kg) male rats of the Wistar strain. Blood ethanol levels were remarkably lower and ethanol elimination stood at 432.6 mg/kg/hr (control, 336.6 mg/kg/hr) in the bezafibrate group (p < 0.01). Blood acetate levels were conversely higher in the bezafibrate group. The fatty acid beta-oxidation activity of liver peroxisome in bezafibrate-treated, clofibrate-treated, or gamma-linolenic acid-treated rats for 4 days was assayed. The activity was 5.8-fold higher in rats given bezafibrate, 5.4-fold in the clofibrate (p < 0.01), and 2.0-fold in the gamma-linolenic acid (p < 0.05). Alcohol dehydrogenase and aldehyde dehydrogenase activity of cytosol in the liver was not induced by the hypolipidemic drugs, but aldehyde dehydrogenase activity in the liver homogenate was induced. From foregoing results, bezafibrate induced in the organism beta-oxidation by peroxisomes and increased H2O2 production, which led to augmented ethanol metabolism by catalase.
Tsukamoto
S
S
Department of Legal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Kanegae
T
T
Isobe
E
E
Hirose
M
M
Shimamura
M
M
Nagoya
T
T
D000085:Acetates / Q000097:blood; D000435:Alcoholic Intoxication / Q000097:blood / Q000378:metabolism; D000447:Aldehydes / Q000097:blood; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D000447:Aldehydes; D005227:Fatty Acids; D008041:Linoleic Acids; D000431:Ethanol; D019787:Linoleic Acid; D001629:Bezafibrate