α-Naphthylisothiocyanate (ANIT) Induced Cholestasis in Rats

In order to distinguish the disorder of bile acid and cholesterol metabolism in α-naphthylisothiocyanate (ANIT)-induced cholestasis, we examined changes in bile acid levels and compositions in bile, serum, feces and urine, as well as cholesterol levels in bile, serum, liver and feces in Wistar male rats (10-13 weeks) after a single oral administration of 100 mg/kg of ANIT. The bile flow and the biliary secretions of cholesterol, phospholipids and bile acids markedly decreased on days 1 and 2 but increased over the normal values on day 4 and then returned to the normal ranges. The fecal excretion of bile acids decreased after the treatment and remained low by day 4 but markedly increased thereafter. The urinary excretion of bile acids changed almost in parallel with serum bile acid level, increasing to 37 mg/day on day 2, 28 mg/day on days 3-4 but to a trace on days 5-6. The urinary bile acids on day 2 mainly consisted of cholic acid while those on days 3-4 and biliary bile acids on day 4 were mostly β-muricholic acid. The serum cholesterol level markedly increased maximally on day 2 and decreased thereafter. The fecal excretion of sterols, cholesterol and coprostanol, decreased on days 1-2 but rather increased thereafter. These data suggest that the cholestasis induced by ANIT is very similar to that in bile duct ligated rats for a short period but not to those ligated for long periods. In addition, the present data suggest that the bile acid independent bile flow is impaired and the daily synthesis of bile acids, especially β-muricholic acid, is increased in the ANIT induced cholestasis.