Xanthine oxidase activity in the circulation of rats following hemorrhagic shock.
Reactive oxygen metabolites generated from xanthine oxidase play an important role in the pathogenesis of ischemia-induced tissue injury. In a hemorrhagic shock model of ischemia-reperfusion, the intracellular enzyme xanthine oxidase was released into the vasculature. This intravascular source of superoxide (O2.-) and hydrogen peroxide (H2O2) interacted reversibly with glycosaminoglycans of vascular endothelium and markedly concentrated xanthine oxidase at cell surfaces, enhancing its ability to produce extensive damage to remote tissues. Rats were made hypotensive by hemorrhage, maintained for 2h, and reinfused with shed blood. Blood samples were obtained prior to hemorrhage and 15, 30, 60, and 90 min after reperfusion for determination of xanthine oxidase (XO), lactate dehydrogenase (LDH), and alanine transaminase (AST). These enzymes were not significantly elevated in control animals. Reperfusion after hemorrhage-induced ischemia resulted in significantly elevated AST and LDH in both low heparin (100 U/h) and high heparin (1000 U/h) groups. Xanthine oxidase was detected in the circulation only after 90 min reperfusion in the low heparin group and was elevated during the entire reperfusion period in the high heparin group. Studies with cultured vascular endothelium showed significant heparin-reversible binding of XO to cellular glycosaminoglycans. These results suggest that XO can gain access to the circulation following ischemia, where it then binds to the vascular endothelial cells to produce site-specific oxidant injury to organs remote from the site of XO release.
Tan
S
S
Department of Pediatrics, University of Alabama at Birmingham 35233-6810.
Yokoyama
Y
Y
Dickens
E
E
Cash
T G
TG
Freeman
B A
BA
Parks
D A
DA
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D005609:Free Radicals; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D007511:Ischemia; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D012771:Shock, Hemorrhagic / Q000201:enzymology*; D013481:Superoxides / Q000097:blood; D014969:Xanthine Oxidase / Q000097:blood*
D005609:Free Radicals; D006025:Glycosaminoglycans; D013481:Superoxides; D006493:Heparin; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase; D000410:Alanine Transaminase