Effect of age and sex on allyl alcohol hepatotoxicity in rats: role of liver alcohol and aldehyde dehydrogenase activities
Rikans, L.E.; Moore, D.R.
Journal of Pharmacology and Experimental Therapeutics 243(1): 20-26
1987
ISSN/ISBN: 0022-3565 PMID: 3668850 Document Number: 304616
Allyl alcohol-induced hepatotoxicity was more severe in old male rats than in young-adult male rats, male rats, as measured by release of hepatic enzymes form injured cells and loss of hepatic microsomal cytochrome P-450. The extnet 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 young adulthood, middle age and old age. ADH activities were 1.7 .+-. 0.1, 2.3 .+-. 0.1 and 2.6 .+-. 0.1 .mu.mol/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 .+-. p0.1 .mu.mol/min/g of liver. There was good correlation (r = 0.99, P < .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 mitochondrial and cytolsolic 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.