MODIFIED HEMOGLOBINS AS A SOURCE OF ACTIVATED OXYGEN SPECIES

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Non-capsulated, non-complexed, chemically modified hemoglobin may act as a "Biological Fenton Reagent", having the potential to catalyze the production of activated oxygen species. Highlights of ongoing studies: 1) Hemoglobin driven hydroxyl radical generation: Results so far have indicated that both modified and unmodified hemoglobins in the presence of a hydrogen peroxide-generating system (Xanthine/Xanthine oxidase) can indeed promote hydroxyl radical formation. 2)Fenton Type Oxidation-Reduction reactions of hemoglobin:One of the recognized effects of hemoglobin involvement in a fenton-like reaction is the transformation of oxyhemoglobin to methemoglobin and vice versa. a. We have monitored methemoglobin formation from three modified hemoglobins over an extended period of time in the presence of enzymatically and nonenzymatically generated H202. b. In other sets of experiments, the ferric (met) form of these hemoglobins were aerobically reduced by NAD(P)H. The modified hemoglobins exhibited appreciable difference in both the degree and rate of reduction by NAD(P)H. c. When the above simple reaction system is expanded to include aniline, para aminophenol is generated in a monoxygenase-like reaction. Modified hemoglobins when added to this system differ appreciably their monoxygenase activity which brought about the hydroxylation of aniline. A number of in and in vivo studies are planned in order to continue to examine the hemoglobin-mediated oxygen radical generation and to determine how these radicals may aggravate "reprefusion injury" in an ischemic animal model,