Nitric oxide-mediated liver injury in the presence of experimental bile duct obstruction


Engin A., Bozkurt B., Altan N., Memis L., Bukan N.

WORLD JOURNAL OF SURGERY, vol.27, no.3, pp.253-255, 2003 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 3
  • Publication Date: 2003
  • Doi Number: 10.1007/s00268-002-6710-0
  • Title of Journal : WORLD JOURNAL OF SURGERY
  • Page Numbers: pp.253-255

Abstract

We investigated the possible mechanism of common bile duct (CBD) obstruction-related liver cell necrosis in a guinea pig model during a 24-hour period of biliary occlusion. A total of 30 male albino guinea pigs were randomly and equally assigned to two groups. Group I underwent sham laparotomy (SL), and group 2 underwent common bile duct ligation (CBDL). All the animals were followed for the first 24-hours after operation. The liver antioxidant defense was examined by measuring liver total superoxide dismutase (TSOD), copper/zine-containing superoxide dismutase (Cu-ZnSOD), manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPx) activities as well as the reduced glutathione (GSH) concentration. Severity of necrosis was assessed by blind quantitation of liver specimens using a histologic scoring system. Histologic evidence of grade +2 hepatocellular necrosis was observed in the CBDL group, as was a more than fourfold increase in plasma nitrite plus nitrate [NOx] concentrations in these animals. Although no significant difference was found between the two groups for liver Cu-ZnSOD activity, the CBDL group showed a marked decrease in MnSOD activity. Concomitant increases in liver GPx activity and the GSH level were measured in the CBDL group. These data supported the hypothesis that excessive production of [NOx] and its derivative peroxynitrite contribute to a coexisting MnSOD deficiency in the mitochondria and lead to liver cell necrosis in cholestatic animals.