Mannosylated superoxide dismutase inhibits hepatic reperfusion injury in rats.
Superoxide anion radical (O2-) is one factor related to ischemia/reperfusion injury to the liver. The sites of O2- production and injury have yet to be determined. Superoxide dismutase (SOD), a specific scavenger for O2-, has an inhibitory effect on injury caused by O2-. SOD is of low molecular weight; hence, it has a short half-life in the circulating blood. Mannosylated SOD is taken up in sinusoidal endothelial cells of the liver by receptor-mediated endocytosis. In rats with an occluded inflow against 70% of the liver for 30 min followed by reperfusion there were elevations of serum aspartate aminotransferase and alanine aminotransferase, and lipid peroxide concentrations in liver tissue were significantly inhibited by intravenous administration of mannosylated SOD compared to treatment with normal saline. Electron microscopic examination showed that mannosylated SOD protected against damage to the sinusoidal endothelial cells caused by ischemia/reperfusion and that conventional SOD had no such protective effect. Thus, O2- produced by ischemia/reperfusion apparently damages sinusoidal endothelial cells, and damage to hepatic parenchymal cells is secondary. Mannosylated SOD deserves further study for possible use in surgical resection of the liver and for liver transplantations.
Kondo
S
S
Second Department of Surgery, Nagasaki University School of Medicine, Japan.
Segawa
T
T
Tanaka
K
K
Izawa
K
K
Hashida
M
M
Kanematsu
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D007275:Injections, Intravenous; D007511:Ischemia / Q000097:blood* / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism / Q000494:pharmacology
D008054:Lipid Peroxides; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase