Absence of hemoprotein-associated free radical events following oxidant challenge of crosslinked hemoglobin-superoxide dismutase catalase.
Crosslinking hemoglobin with superoxide dismutase and catalase (PolyHb-SOD-CAT) helps to limit free radical reactivity of modified hemoglobin red blood cell substitutes. In the present study, in vitro oxidant challenge experiments were performed with exogenous hydrogen peroxide (H2O2) and xanthine oxidase-derived superoxide (O2.-). PolyHb-SOD-CAT was compared to PolyHb for the presence of secondary hemoprotein-free radical events. PolyHb-SOD-CAT prevents ferrylhemoglobin formation, measured as Na2S-induced absorbance at 620 nm. Similarly, PolyHb-SOD-CAT inhibited ferrozine-detectable iron release at high oxidant-heme ratios. The formation of oxygen radicals, monitored by salicylate hydroxylation, was prevented at high oxidant-heme ratios with PolyHb-SOD-CAT. The peroxidation of liposomal membranes was also inhibited in PolyHb-SOD-CAT mixtures subject to oxidant challenge. These results show that PolyHb-SOD-CAT prevents secondary hemoprotein-associated free radical events. This new type of modified hemoglobin oxygen carrier with antioxidant activity may reduce the potential toxicity of hemoglobin-based substitutes in certain applications, especially during reperfusion of ischemic tissues.
D'Agnillo
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Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, PQ, Canada.
Chang
T M
TM
D000818:Animals; D001802:Blood Substitutes; D002374:Catalase / Q000138:chemical synthesis / Q000737:chemistry / Q000187:drug effects*; D002417:Cattle; D003432:Cross-Linking Reagents / Q000737:chemistry; D005297:Ferrozine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors / Q000378:metabolism; D005976:Glutaral / Q000737:chemistry; D006454:Hemoglobins / Q000138:chemical synthesis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006900:Hydroxylation; D007501:Iron / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000737:chemistry; D020156:Salicylic Acid / Q000032:analysis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000138:chemical synthesis / Q000737:chemistry / Q000187:drug effects*; D013481:Superoxides / Q000138:chemical synthesis / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000737:chemistry
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D016166:Free Radical Scavengers; D006454:Hemoglobins; D008081:Liposomes; D010743:Phospholipids; C037158:polyhemoglobin; D013481:Superoxides; C066317:ferryl iron; D005297:Ferrozine; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; C086134:polyhemoglobin-superoxide dismutase-catalase; D014969:Xanthine Oxidase; D020156:Salicylic Acid; D005976:Glutaral