Study to Adapt Clinical Pathology Tests to Detect Toxic Cholestasis in Experimental Animals

摘要

Methyltestosterone (MT) and ethinyl estradiol (EE) were administered to adult dogs and rabbits in sequentially increasing doses for periods of 13 and 20 weeks respectively. No biochemical evidence of hepatic dysfunction was recognized in dogs throughout the period of treatment and histologic changes were minimal, consisting of enlargement of individual hepatocytes located in the periphery of the lobule. In rabbits, however, there were significant increases in serum y-glutamyltransferease and aminotransferases after 2 weeks of treatment and with progressively higher doses, there were marked increases in serum bile acid concentrations and in BSP retention. Significantly histopathologic lesions of the liver were observed with both steroid-treated groups of rabbits. The most severe lesions were seen in the EE group and consisted of bile duct proliferation, periportal mononuclear cell infiltration, and perilobular fibrosis. These studies indicate that the dog is remarkably resistant and the rabbit susceptable to hepatic dysfunction induced by MT and EE.