Hepatic regenerative enzyme activity after diffuse injury with galactosamine: relationship to histologic alterations.
Massive liver injury with 1000 mg/kg D-galactosamine was followed by a broad peak of thymidine kinase (TK) activity over 62 to 120 hours. The highest mean value was a 29-fold increase in activity. Three peaks of ornithine decarboxylase (ODC) activity were observed over the same time span. The first peak occurred at 45 hours, showing a sevenfold to eightfold increase in activity. Histologic evidence of necrosis peaked at 12 to 24 hours and was prominent over 54 hours. Periportal inflammation in response to the cellular injury was prominent from 12 to 96 hours and peaked at 45 to 62 hours. The curve of mitoses peaked at the same time as that of TK activity but was only 68% as extensive. The first peak of ODC activity occurred before there was any significant presence of mitoses or of TK activity. A smaller dose of 400 mg/kg resulted in a narrow peak of TK activity at 62 hours that was a 37-fold increase in activity. The total TK response was 43% of that seen after the larger dose, about in proportion to the dose given. The first ODC peak, representing the earliest evidence of regeneration, was earlier and more prominent after the 400 mg/kg dose. On the basis of areas under the curves, the amounts of necrosis and of periportal inflammation after 400 mg/kg were 36% of those seen after 1000 mg/kg. Corresponding figures for other response curves were 29% for mitoses, 33% for serum SGPT, and 71% for total ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Zieve
L
L
Veterans Administration, Medical Center, Minneapolis, MN.
Anderson
W R
WR
Dozeman
R
R
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005688:Galactosamine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D009955:Ornithine Decarboxylase / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013937:Thymidine Kinase / Q000032:analysis*
D005688:Galactosamine; D000410:Alanine Transaminase; D013937:Thymidine Kinase; D009955:Ornithine Decarboxylase