Effect of age and sex on allyl alcohol hepatotoxicity in rats: role of liver alcohol and aldehyde dehydrogenase activities.
Allyl alcohol-induced hepatotoxicity was more severe in old male rats than in young-adult male rats, as measured by release of hepatic enzymes from injured cells and loss of hepatic microsomal cytochrome P-450. The extent of toxicity in female rats was greater than in males and was unaffected by aging. The purpose of this study was to examine possible causes for these differences. The activity of alcohol dehydrogenase (ADH) with allyl alcohol as substrate was measured in liver cytosolic fractions of rats at ages representing young adulthood, middle age and old age. ADH activities were 1.7 +/- 0.1, 2.3 +/- 0.1 and 2.6 +/- 0.1 mumol/min/g of liver in male rats aged 4, 14 and 25 months, respectively. ADH activities in young-adult and old female rats were 3.8 +/- 0.1 and 3.7 +/- 0.1 mumol/min/g of liver. There was a good correlation (r = 0.99, P less than .001) between liver ADH activity and allyl alcohol-induced hepatotoxicity, measured as the release of sorbitol dehydrogenase into the bloodstream. Cytosolic free NAD+/NADH ratios in male rats were not significantly different among the three age groups; the ratios were lowest in young-adult female rats. Low Km aldehyde dehydrogenase activities in liver mitochondrial and cytosolic fractions were similar among the three age groups of male rats, and the activities in female rats were not substantially different. The results indicated that increased ADH activity is the principal cause of the age-associated enhancement of allyl alcohol hepatotoxicity in male rats.
Rikans
L E
LE
Department of Pharmacology, College of Medicine, University of Oklahoma, Oklahoma City.
Moore
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DR
D000433:1-Propanol / Q000633:toxicity; D000375:Aging; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D005260:Female; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D020005:Propanols; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013347:Subcellular Fractions / Q000201:enzymology
D007773:Lactates; D020005:Propanols; D011773:Pyruvates; D009243:NAD; C006463:allyl alcohol; D000433:1-Propanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase