Effect of chronic administration of taurolithocholate on bile formation and liver ultrastructure in the rat

In some cholestatic syndromes, lithocholic acid (LCA) has been identified in serum and bile and might play a role in the pathogenesis of cholestasis. Thus, we examined the effect of chronic LCA administration on hepatobiliary function in rats. The taurine-conjugate of LCA (TLCA) was given to male rats at the dose of 50 mg/kg body weight i.v. twice daily for 18 days. Bile flow, biliary secretion rate of bile acids, phospholipids and cholesterol, measured 15 h after the last injection, were normal with the exception of phospholipid, which was significantly higher when compared to controls. Individual bile acids measured by GLC showed that the contribution of chenodeoxycholic and muricholic acids increased while that of cholic acid decreased. By electron microscopy, bile canalicular structures appeared normal except for a widening of the pericanalicular ectoplasm. Evaluation of hepatobiliary function 1 h after an additional injection of TLCA to rats that received the bile acid for 18 days, resulted in the typical acute cholestatic response. Thus chronic administration of TLCA does not influence the acute cholestatic effect of TLCA.