Effect of allyl alcohol on xanthine dehydrogenase activity in the perfused rat liver.
Xanthine oxidase has been implicated in the production of reactive oxygen species and cell injury produced by various toxic compounds. Since allyl alcohol injuries the liver by an oxygen-dependent mechanism, we examined the actions of this hepatotoxicant on the conversion of xanthine dehydrogenase into xanthine oxidase in perfused livers. A microassay for NAD(+)-dependent xanthine dehydrogenase, based on measuring the production of NADH fluorometrically under anaerobic conditions, was developed and used to examine the actions of allyl alcohol on this activity in periportal and pericentral regions of the liver lobule. The oxygen-dependent activity, xanthine oxidase, was monitored in whole liver homogenates by uric acid formation at 302 nm under aerobic conditions. Perfusion of the liver with allyl alcohol (350 microM) increased xanthine oxidase and decreased xanthine dehydrogenase in whole liver consistent with the hypothesis that allyl alcohol enhanced calcium-dependent proteolytic conversion of the NAD(+)-dependent to the O2-dependent form. Xanthine dehydrogenase was higher in pericentral than in periportal regions of the liver lobule and tended to decrease selectively in periportal zones of livers exposed to allyl alcohol. O2 uptake was stimulated transiently by allyl alcohol followed by subsequent inhibition of respiration. These results are consistent with the idea that conversion of NAD(+)-dependent xanthine dehydrogenase to xanthine oxidase is involved in the zone-specific hepatotoxicity of allyl alcohol.
Brown
P C
PC
Department of Pathology, University of Maryland School of Medicine, Baltimore.
Thurman
R G
RG
Belinsky
S A
SA
Kauffman
F C
FC
D000433:1-Propanol / Q000633:toxicity; D000818:Animals; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D020005:Propanols; D051381:Rats; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D020005:Propanols; C006463:allyl alcohol; D000433:1-Propanol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase