Experimental Study on Hepatic Cytoprotective Function of Nitric Oxide in Obstructive Jaundice

Mitsugi Shimoda

Second Department of Surgery, Dokkyo University School of Medicine

Obstructive jaundice is closely associated with endotoxemia. Bacterial endotoxin (LPS) and proinflammatory cytokines induce nitric oxide (NO) synthase in various organs in vivo as well as in a variety of cells in vitro. I investigated whether NO production is increased in obstructive jaundice by determining NO₂/NO₃ levels in portal plasma of common bile duct-ligated rats. While the NO₂/NO₃ levels in portal plasma of control rats did not change during the observation, a gradual increase up to day 7 was seen after the ligation. Although the NO synthase mRNA in the liver was undetectable before the bile duct ligation, it was substantially induced by day 7 following the ligation. A decreased peripheral blood flow in the liver was observed in the bile duct-ligated rats, which was further reduced by treatment of the rats with the NO synthase inhibitor, L-NAME. I also investigated the effect of bile acids on the induction of NO synthase in LPS-stimulated J774 macrophages.Whole bile from control rats and, to a lesser extent, from the bile duct ligated-rats inhibited NO synthase induction in macrophages. Five different bile acids (cholic acid, lithocholic acid, chenodeoxycholic acid and ursodeoxycholic acid), all inhibited NO synthase with similar dose dependency. In conclusion, obstructive jaundice is associated with increased NO production which is derived from induced NO synthase. Elevated NO may play an important role in obstructive jaundice, especially in the peripheral blood flow in the liver.

Key words
nitric oxide, obstructivejaundice, bile acid, endotoxin, peripheral blood flow in the liver

Reprint requests
Mitsugi Shimoda Second Department of Surgery, Dokkyo University School of Medicine
880 Kitakobayashi. Mibumachi, Shimotsuga-gun, Tochigi, 321-02 JAPAN

Accepted
October 11, 1995

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