Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined, A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1 mu mol/100 g body wt. per min, In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS, Secondly, rye also examined whether or not UDCA protects against endotoxemia. In this experiment, fionlabeled LPS was administered via the portal vein and its peripheral concentration was then measured, In UDCA-treated rats, the cndatoxin concentration was significantly lower, Finally, to elucidate the effect of UDCA on Kupffor cells, serum tumor necrosis factor (TNF-alpha) was measured, But UDCA had no effect on the TNF-alpha level, These findings thus demonstrate that the intravenous administlation of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocgtes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.