Effect of hepatic failure toxins on liver thymidine kinase activity and ornithine decarboxylase activity after massive necrosis with acetaminophen in the rat.
After massive liver injury with acetaminophen, subcoma doses of hepatic failure toxins (NH+4, dimethyl disulfide [----methanethiol], octanoic acid) depressed liver thymidine kinase (TK) activity by 78%, 85%, and 90%, respectively, and ornithine decarboxylase (ODC) activity by 40%, 83%, and 78%, respectively. Twenty-four hours after the last dose of the toxins the depressant effects were still evident. The doses of dimethyl disulfide and octanoic acid required for these depressant effects on TK activity were less than half those required for similar effects previously reported after two-lobe hepatectomy of normal rat liver. The dose of NH+4 required was not reduced. None of the toxins depressed ODC activity after the hepatectomy, in contrast to their depressant effects after acetaminophen. Thus doses of the hepatic failure toxins that were about one fourth to one half those needed to induce coma in normal rats inhibited activity of regenerative enzymes after acute massive liver injury with acetaminophen. The effects were persistent for at least 24 hours. These observations may have relevance to the lack of regeneration observed commonly after fulminant hepatic failure in humans.
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004220:Disulfides / Q000633:toxicity*; D006498:Hepatectomy; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D009336:Necrosis; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013937:Thymidine Kinase / Q000378:metabolism*
D002210:Caprylates; D004220:Disulfides; D000644:Quaternary Ammonium Compounds; D000082:Acetaminophen; C021181:dimethyl disulfide; D013937:Thymidine Kinase; D009955:Ornithine Decarboxylase; C031492:octanoic acid