Changes in hepatic function tests to induced toxicity in the bovine liver

Graded hepatic damage was induced in mature lactating dairy cows to measure the sensitivity of several hepatic diagnostic tests. In a preliminary study, cows were dosed with .05, .10 and .20 ml/kg body weight of carbon tetrachloride. Extreme changes occurred in hepatic tests by 24 h post-dosing, and all died by 35 h with massive diffuse centrilobular necrosis of hepatic cord cells. Dosing was decreased to induce non-fatal hepatic changes. Cows in Groups 1, 2, 3 and 4 were orally dosed with .002, .004, .006 or .01 ml/kg body weight of carbon tetrachloride, respectively. Serum enzymes of hepatic origin, bilirubin, plus bromosulfophthalein dye clearance were assayed before dosing and up to d 14 post-dosing. Liver biopsies were performed 24 h post-dosing for histological evaluation and cytochrome P-450 content. Hepatic concentrations of cytochrome P-450 were decreased in all the dosed cows. Serum activities of sorbitol dehydrogenase and gamma-glutamyl transferase were elevated in cows of Groups 3 and 4 and glutamic-oxaloacetic transaminase in cows of Group 4 by 24 h. Serum alkaline phosphatase, glutamic-pyruvate transaminase, lactate dehydrogenase, bilirubin, urobilinogen and bromosulfophthalein dye clearance were not significantly different. Mild to moderate diffuse centrolobular necrosis was observed in livers of cow of Groups 3 and 4, but no pathological changes were seen in Groups 1 and 2.