Long-term administration of PGE1 increases liver fibrosis and collateral blood flow in bile-duct-ligated rats.

BACKGROUND/AIMS: The aim of this study was to assess the effect of early and chronic administration of a prostaglandin E1 analogue (misoprostol) in the prevention of liver fibrosis and portal hypertension.

METHODS

Liver fibrosis was induced by bile duct ligation. Controls had a sham operation. Bile-duct-ligated rats were divided into two groups: placebo (vehicle only) and misoprostol (10 microg/d by gavage) for 4 weeks after surgery. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline content and serum hyaluronate. Systemic and splanchnic hemodynamics were evaluated including spleno-renal shunt blood flow by the transit-time ultrasound technique.

RESULTS

Mean arterial pressure was significantly lower in the misoprostol group (p<0.01). There was an unexpected increase in fibrosis parameters in the misoprostol group compared to the placebo group, e.g. area of fibrosis: 9.5+/-4.0 vs 15.0+/-8.1% (p<0.05). Spleno-renal shunt blood flow was significantly higher in the misoprostol group than in the placebo group (4.6+/-3.7 vs 2.2+/-2.0 ml/min, p<0.05) while portal pressure was unchanged.

CONCLUSIONS

The early and chronic administration of misoprostol enhances porto-collateral circulation blood flow and the development of liver fibrosis in bile-duct-ligated rats.