Acetaminophen hepatotoxicity in aging rats.
Severity of liver damage 24 hr after i.p. administration of acetaminophen in doses of 0.4 and 0.8 g/kg was evaluated in male Fischer 344 rats at 4, 14 and 25 months of age. Both doses of acetaminophen produced significant elevations of serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities in 4-month-old rats. Enzyme release was somewhat diminished in old age. Hepatic glutathione (GSH) and microsomal cytochrome P-450 concentrations were decreased in rats that received 0.8 g/kg of acetaminophen. The decreases occurred in young-adult and middle-aged rats, but not in old rats. The results demonstrated that old age does not enhance the hepatotoxic effects of acetaminophen in male Fischer 344 rats.
Rikans
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LE
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Moore
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DR
D000082:Acetaminophen / Q000633:toxicity*; D000375:Aging / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione