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Ornithine Decarboxylase, Serum Isocitrate Dehydrogenase and Clinical Chemisty Changes during Thioacetamide-Induced Hepatotoxicity in a Calf^{1 ,2,}

Ohio Agricultural Research and Development Center, Wooster 44691

Abstract

Our previous studies showed that poly-brominated 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. Histopathologic alterations in the liver included centrilobular necrosis with congestion and subcapsular micro-hemmorrhage. 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.

¹ Approved for publication as Journal Article No. 204-80 of the Ohio Agricultural Research and Development Center, Wooster 44691.

² This project was supported in part by Contract No. 223-75-7015, Department of Health, Education, and Welfare, FDA, Bureau of Veterinary Medicine. We acknowledge the capable technical assistance of C. W. Clark.

³ Dept. of Dairy Sci.

⁴ Dept. of Vet. Sci.