Studies of alpha-napthylisothiocyanate-induced hepatic disturbance.

In order to clarify the mechanism of alpha-naphthylisothiocyanate (ANIT) induced cholestasis in rats, a few hepatic changes seen after administration of ANIT 80 mg/kg body weight were examined in relation to time. To clarify changes in the bile production system and bile flow, the concentrations of bile acid and bicarbonate, as well as of sodium in the bile, were measured after infusion of secretin and taurocholic acid. The canalicular bile flow was estimated by measuring the biliary clearance of erythritol-C14. To assess hepatocellular injury, the levels of cytochrome P-450 in the microsome of hepatocytes and protein synthesis in the liver were estimated. It seems that ANIT is activated in the drug metabolising system through cytochrome P-450 in the liver, and significant changes are produced in both the bile acid metabolism and its transport system. Bile acid-independent bile flow in the canaliculus was inhibited, too. Hence, both the bile ductules and the bile ducts are functionally and histologically disturbed.