Effect of hepatic failure toxins on regenerative enzymes in the liver after injury with galactosamine in the rat.
Hepatic thymidine kinase (TK) and ornithine decarboxylase (ODC) activities were used to quantify the regenerative response to injury with galactosamine. After massive damage with 1000 mg/kg galactosamine, TK activity (DNA synthesis) peaked between 62 and 120 hours. This peak of activity was depressed as much as 91% by six subcoma doses of dimethyl disulfide (DMDS) given between 24 hours and 64 hours after galactosamine administration. Similar doses of octanoic acid (OA) had no effect, and doses of NH4Cl had no effect except at 120 hours. The first peak of ODC activity (initiation of cell growth) at 45 hours was depressed about 60% by six subcoma doses of NH4Cl or DMDS injected between 27 hours and 42 hours. OA again had no effect. After 400 mg/kg galactosamine, a narrow but high peak of TK activity occurred at 62 hours. This peak of activity was depressed more than 50% by six subcoma doses of NH4Cl, OA, or DMDS given between 24 hours and 54 hours. The first peak of ODC activity at 36 hours was similarly reduced by more than 50% by similar doses of each of the toxins given between 24 hours and 34 hours. The overt neurologic effects of the toxins were dissipated within 1 hour of each injection. The depressive effect of NH4Cl and OA on TK and ODC activities during regeneration after massive centrolobular injury with acetaminophen was more consistently present and more extensive than that seen after injury with galactosamine.
Zieve
L
L
Veterans Administration Medical Center, Minneapolis, MN.
Dozeman
R
R
D000082:Acetaminophen; D000643:Ammonium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002210:Caprylates / Q000008:administration & dosage / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology; D005688:Galactosamine; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D002210:Caprylates; D004220:Disulfides; D065108:Ornithine Decarboxylase Inhibitors; D000643:Ammonium Chloride; D000082:Acetaminophen; C021181:dimethyl disulfide; D005688:Galactosamine; D013937:Thymidine Kinase; C031492:octanoic acid