STUDIES OF "ALPHA-NAPTHYLISOTHIOCYANATE-INDUCED HEPATIC DISTURBANCE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 27  (6) , 457-464
Abstract
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 Na 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. ANIT is probably activated in the drug metabolizing system through cytochrome P-450 in the liver, and significant changes are produced in the bile acid metabolism and its transport system. Bile acid-independent bile flow in the canaliculus was inhibited, too. The bile ductules and the bile ducts are functionally and histologically disturbed.