Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase.
The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.
Ogura
Y
Y
First Department of Surgery, Mie University School of Medicine, Japan.
Takagi
K
K
Kawarada
Y
Y
Mizumoto
R
R
D000818:Animals; D002779:Cholestasis / Q000503:physiopathology*; D003067:Coenzymes; D004285:Dogs; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D006498:Hepatectomy; D007728:Kupffer Cells / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis; D011137:Polystyrenes / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000401:mortality / Q000503:physiopathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D015996:Survival Rate; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D003067:Coenzymes; D004731:Endotoxins; D005609:Free Radicals; D008054:Lipid Peroxides; D011137:Polystyrenes; D014451:Ubiquinone; D013482:Superoxide Dismutase; C068153:superoxide dismutase-poly(styrene co-maleic acid butyl ester); D001619:beta-N-Acetylhexosaminidases; C024989:coenzyme Q10