Effects of acute ethanol administration on the hepatic xanthine dehydrogenase/oxidase system in the rat.
Administration of ethanol (5 g/kg p.o.) to female Sprague-Dawley rats resulted in conversion of a portion of hepatic xanthine dehydrogenase to xanthine oxidase 12 hr after treatment. Conversion was partly reversed in vitro by treatment of hepatic 100,000 X g supernatant with dithiothreitol, whereas pretreatment of rats with pyrazole (100 mg/kg i.p.) prevented conversion 18 hr after ethanol administration. Incubation of acetaldehyde with rat liver supernatant at 37 degrees C converted xanthine dehydrogenase to xanthine oxidase in a dose-dependent manner, whereas incubation of ethanol with rat liver supernatant did not lead to conversion. Acetaldehyde-induced conversion in vitro was reversed by treatment with dithiothreitol, and was partially blocked by addition of equimolar concentrations of reduced glutathione. These data suggest that biotransformation of ethanol is required for conversion of hepatic xanthine dehydrogenase to xanthine oxidase. Because xanthine oxidase utilizes molecular oxygen to produce superoxide radical, ethanol-induced conversion of xanthine dehydrogenase to xanthine oxidase could contribute to the enhanced lipid peroxidation reported previously after administration of a single dose of ethanol.
Sultatos
L G
LG
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Newark.
D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D019803:Glutathione Disulfide; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D011720:Pyrazoles; D000431:Ethanol; C031280:pyrazole; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D007658:Ketone Oxidoreductases; D005978:Glutathione; D000079:Acetaldehyde; D004229:Dithiothreitol; D019803:Glutathione Disulfide