The effect of bile duct ligation for 5 days on the hepatic transport of sulfated and nonsulfated bile acids was studied. Tracer doses of radioactive bile acids [3H]taurochenodeoxycholate-3-sulfate [3H]chenodeoxycholate-3-sulfate, [ 3 H ] t a ~r ~~h e n ~d e ~~y ~h o l i ~ acid and ['4C]taurocholic acid were injected 90 min after relief of obstruction when the plasma total bile acid concentration had reverted to normal. Plasma clearance and biliary excretion of sulfated bile acids were lower than those of nonsulfated bile acids, particularly in the cholestatic rats (p < 0.02). For each bile acid, hepatic transport in the cholestatic rats was significantly reduced compared with the control rats.
["H]Chenodeoxycholate-3-sulfate and [3H]taurochenodeoxycholic acid were partially metabolized to [3H]taurochenodeoxycholate-3-sulfate prior to biliary excretion. This data suggests that the hepatic transport system for sulfated bile acids is less efficient and more easily impaired by cholestasis than that for nonsulfated bile acids.
Sulfation of bile acids is a quantitatively important pathway of bile acid metabolism in patients with liver disease including cholestasis (1-3). Chenodeoxycholic acid is preferentially sulfated compared to cholic acid (4) and is the principal bile acid sulfate in plasma and urine (5,6). Little, however, is known about the hepatic transport of sulfated bile acids. The present study was, therefore, designed to investigate the plasma clearance and biliary excretion of tracer doses of radioactive sulfated and nonsulfated chenodeoxycholic acids in cholestatic rats immediately after relief of bile duct obstruction. With this model, it was possible to investigate the effect of structural changes in bile acids on their hepatic transport and also the influence of cholestasis.