Nitric oxide-mediated liver injury in the presence of experimental bile duct obstruction.
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 1 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/zinc-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.
Engin
Atilla
A
Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500, Besevler, Ankara, Turkey. atillaengin@ttnet.net.tr
Bozkurt
B Sükrü
BS
Altan
Nilgün
N
Memiş
Leyla
L
Bukan
Neslihan
N
D000818:Animals; D003137:Common Bile Duct Diseases / Q000503:physiopathology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D022781:Hepatocytes / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D009336:Necrosis; D009569:Nitric Oxide / Q000502:physiology*; D011897:Random Allocation
D009569:Nitric Oxide