Ornithine decarboxylase, serum isocitrate dehydrogenase and clinical chemistry changes during thioacetamide-induced hepatotoxicity in a calf.
Our previous studies showed that polybrominated biphenyl (PBB) induced hepatic microsomal cytochrome P-450 in dairy cattle but did not elevate hepatic cytosolic ornithine decarboxylase or serum isocitrate dehydrogenase. These enzymes would be expected to increase during hepatotoxic injury and regeneration. Thus, PBB appeared to be a hepatotoxin in rats but not in cattle. In order to identify and confirm the response capability of bovine liver to hepatotoxins, we administered thioacetamide, a hepatotoxin known to induce hepatonecrosis, to a dairy calf. A progression of clinical signs of toxicosis was evident until the animal was moribund by 23 hr postdosing. Histolopathologic alterations in the liver included centrilobular necrosis with congestion and subcapsular microhemmorrhage. Marked changes in serum protein profiles were not noted. However, distinct increases in serum Fe and bilirubin occurred with progressing toxicosis, as did sharp declines in glucose and triglycerides. Serum lactic dehydrogenase, alkaline phosphatase, glutamic-oxaloacetic transaminase, isocitrate dehydrogenase and glutamic-pyruvate transaminase were elevated. Elevation of ornithine decarboxylase was dramatic when compared to the level in normal fetal bovine liver. From studies of its kinetic properties, bovine liver ornithine decarboxylase appears to have an apparent Km for ornithine decarboxylase of .45 mM. Liver homogenates from PBB-treated animals did not form inhibitors to ornithine decarboxylase. Compared with the thioacetamide-treated calf, the normal adult bovine, pregnant adult and 6-month fetus had relative activities of .2 .4 and 5.8%, respectively. These studies show that ornithine decarboxylase is low in liver of normal cattle, but is elevated markedly by agents that cause hepatonecrosis.
D000081:Acetamides / Q000009:adverse effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000139:chemically induced / Q000201:enzymology*; D056486:Chemical and Drug Induced Liver Injury; D007521:Isocitrate Dehydrogenase / Q000097:blood*; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000662:veterinary*; D008297:Male; D009336:Necrosis; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D013853:Thioacetamide / Q000009:adverse effects*
D000081:Acetamides; D001786:Blood Glucose; D001798:Blood Proteins; D013853:Thioacetamide; D007521:Isocitrate Dehydrogenase; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase