EFFECT OF URSODEOXYCHOLIC ACID ADMINISTRATION ON BILE-DUCT PROLIFERATION AND CHOLESTASIS IN BILE-DUCT LIGATED RAT

The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study exam ined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/d ay) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline p hosphatase, and gamma-glutamyltransferase (GGT) was significantly lowe r (P < 0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P < 0. 001) in group A. Moreover, the co ntrol of BA in bile was reduced also (P < 0. 02). Conversely, serum ch olesterol levels were not different between the two groups. Histologic al examination showed that the number of ductular cells in the portal areas was significantly (P < 0. 001) reduced in UDCA-treated as compar ed to saline-treated rats. The replication activity, assessed as the n umber of bromodeaxyuridine-positive cells, was also significantly lowe r in treated animals (33 +/- 11 vs 64 +/- 22 per 1000 cells; P < 0. 00 1). Lobular bile ductules were three times larger in group B, and extr ahepatic duct measurements confirmed this increase in size of the larg er biliary ducts (P < 0.001). These findings demonstrate that UDCA red uces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation. These data support the benefici al effect of UDCA treatment in chronic cholestatic disease.