Abstract

Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation.