Inhibition of posthemorrhagic transfusion-induced gastric injury by a long-acting superoxide dismutase derivative.
Although oxygen-free radicals have been postulated to play an important role in the pathogenesis of gastric mucosal injury induced by posthemorrhagic blood transfusion, direct evidence supporting this hypothesis is lacking. Superoxide dismutase (SOD) has been shown to inhibit oxygen toxicity in vitro in various types of cell injury. However, in some cases, oxidative tissue injury cannot be decreased efficiency predominantly due to its rapid elimination by renal glomerular filtration. To overcome such frustrating situations, we have synthesized a SOD derivative that circulates bound to albumin with a half-life of 6 hr. When blood was withdrawn from the rat (22 ml/kg) for 30 min followed by transfusion of the extracted blood, marked gastric mucosal lesions occurred within 30 min after transfusion. Intravenously injected SOD derivative markedly decreased gastric mucosal injury. Kinetic analysis using 125I-labeled albumin revealed that the vascular permeability of the stomach increased significantly after transfusion by a SOD derivative inhibitable mechanism. Thus, superoxide radical and/or its metabolite(s) play a critical role in the pathogenesis of posthemorrhagic transfusion-induced gastric injury.
Obayashi
H
H
Department of Surgery, Kumamoto University Medical School, Japan.
Koshi
S
S
Miyauchi
Y
Y
Inoue
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology; D008163:Luminescent Measurements; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D011137:Polystyrenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D065227:Transfusion Reaction
D008298:Maleates; D011137:Polystyrenes; C059316:poly(styrene-co-maleic acid)butyl ester; D013482:Superoxide Dismutase