J. C. White

Bio: J. C. White is an academic researcher. The author has contributed to research in topics: Heinz body. The author has an hindex of 1, co-authored 1 publications receiving 75 citations.

Oxidation of Phenyl-Hydrazines in the Presence of Oxyhæmoglobin and the Origin of Heinz Bodies in Erythrocytes

Abstract: Oxidation of Phenyl-Hydrazines in the Presence of Oxyhaemoglobin and the Origin of Heinz Bodies in Erythrocytes

Oxidative hemolysis and precipitation of hemoglobin. i. heinz body anemias as an acceleration of red cell aging

Abstract: The propensity of certain chemicals and drugs to induce hemolytic anemias has been a subject of much interest for almost a century (1-4). The majority of substances so active are aromatic compounds containing amino-, nitro-, or hydroxy groups, although a number of inorganic compounds (e.g., hydroxylamines, nitrates, nitrites and chlorates) are also active (1-4). Such compounds usually cause red cell injury without evidence of specific toxicity to other cells or tissues. The hemolytic process is characterized by two rather distinctive features in the affected red cells: 1) the appearance of l)rownish or greenish derivatives of hemoglobin, including methemoglobin, according to most (3) but not all (4) reports; and 2) the formation within red cells of water-insoluble, stainable granules, generally termed Heinz bodies. There has been extensive debate as to the identity and significance of the hemoglobin discoloration following the adiministration of these compounds. Much of the disagreement may be attributed to the fact that many of the observations have been made in vivo, where pigments initially produced by the compound are mixed with the various products of hemoglobin catabolism. Furthermore, the fact that certain of the pigments produced, such as miiethemoglobin, are reversible, whereas certain others (including so-called sulfhemoglobin) are not (3), has undoubtedly led to conflicting observations. In those few studies where early, sequential observations have been made, methemoglobinemia has been striking albeit transient (5, 6). Studies of compounds such as phenylhydrazine, which are active against red cells in vitro as well as in vivo, have shown that hemoglobin may be changed in part to methemo-

The oxidation of phenylhydrazine: superoxide and mechanism.

Abstract: The oxidation of phenylhydrazine in buffered aqueous solutions is a complex process involving several intermediates. It can be initiated by metal cations, such as Cu2+; in which case EDTA acts as an inhibitor. It can also be intiated by oxyhemoglobin; in which case chelating agents do not interfere. Superoxide radical is both a product of this reaction and a chain propagator. The formation of O2- could be demonstrated in terms of a reduction of nitroblue tetrazolium, which was prevented by superoxide dismutase. The importance of O2- in carrying the reaction chains was shown by the inhibition of phenylhydrazine oxidation by superoxide dismutase. Hydrogen peroxide accumulated during the reaction and could be detected with catalase. The progress of this oxidation could be monitored in terms of oxygen consumption and by following increases in absorbance at 280 or 320 nm. The oxidation was markedly autocatalytic and superoxide dismutase had the effect of extending the lag period. The absorbance at 280 nm was due to an intermediate which first accumulated and was then consumed. This intermediate appears to be benzendiazonium ion. The absorbance at 320 nm was due to a stable product, which was not identified. The time course of oxygen consumption paralleled the increase in absorbance at 320 nm and lagged behind the changes at 280 nm. Exogenous benzenediazonium ion accelerated the oxidation of phenylhydrazine and eliminated the lag phase. Benzenediazonium ion must therefore react with phenylhydrazine to produce a very reactive intermediate, possibly phenyldiazene. A mechanism was proposed which is consistent with the data. The intermediates and products of the oxidation of phenylhydrazine include superoxide radical, hydrogen peroxide, phenylhydrazyl radical, phenyldiazene, and benzenediazonium ion. This is a minimal list: others remain to be detected and identified. It appears likely that the diverse biological effects of phenylhydrazine are largely due to the reactivities of these intermediates and products.

Free-radical production and oxidative reactions of hemoglobin

Abstract: Mechanisms of autoxidation of hemoglobin, and its reactions with H2O2, O2-, and oxidizing or reducing xenobiotics are discussed. Reactive intermediates of such reactions can include drug free radicals, H2O2, and O2-, as well as peroxidatively active ferrylhemoglobin and methemoglobin-H2O2. The contributions of these species to hemoglobin denaturation and drug-induced hemolysis, and the actions of various protective agents, are considered.