EFFECT OF SODIUM TAUROURSODEOXYCHOLATE (UR-906) ON LIVER DYSFUNCTION IN BILE DUCT-LIGATED RATS

We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the e ffect of dehydrocholic acid. UR-906 (30-180 mu mol/kg) and dehydrochol ic acid (180 mu mol/kg) were intravenously given once daily for consec utive 20 days in rats and the common bile duct was ligated for the las t 10 days. On the next day after the last test drug administration, se rum biochemical and plasma hemostatic Variables were determined. UR-90 6 significantly ameliorated the elevation of serum cholesterol, phosph olipid, bilirubin and bile acid concentrations in bile duct-ligated ra ts. UR-906 significantly suppressed the prolongation of plasma prothro mbin time and activated partial thromboplastin time. Furthermore, UR-9 06 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause signif icant changes in any of the variables examined in this model. These re sults suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders. (C) 1997 Elsevier Science B.V.