OXIDATIVE HEMOLYSIS AND PRECIPITATION OF HEMOGLOBIN. I. HEINZ BODY ANEMIAS AS AN ACCELERATION OF RED CELL AGING *

Abstract

Phenylhydrazine and related redox compounds which cause Heinz body anemias in vivo were studied as to their effects in vitro on red cells and on solutions of crystalline human hemoglobin. With both substrates the following sequence of changes in hemoglobin were observed: (1) methemoglobin was formed until a new, hemoglobin[image]methemoglobin equilibrium was acheived; (2) a fast-moving component of hemoglobin on electrophoresis and resin column chromatography appeared; (3) a group of soluble, poorly soluble, and insoluble known to green "sulfhemoglobin-like," denatured pigments appeared; (4) these denatured products of hemoglobin precipitated into coccoid bodies ranged up to 2 or 3 [mu] in diameter with properties identical to those of Heinz bodies. It is concluded that Heinz bodies represent granules of precipitated hemoglobin. Drugs and chemicals active in this respect have the property of reacting with molecular oxygen, probably to form oxidant intermediates or free radicals capable of oxidizing hemoglobin and other intracellular components. These drugs thereby transmit the high oxidation potential of oxygen to cellular components in a cell containing uniquely high concentrations of oxygen and a substance, hemoglobin, which catalyzes the activation of the drug. In the course of several days red cells or hemoglobin incubated under oxygen alone underwent the same changes, including Heinz body formation, as those which occurred in minutes or hours in the presence of the oxidant drugs. Since some of these changes have been identified with aging in vivo, it appears that senescence, in the red cell at least, involves the irreversible oxidation of hemoglobin and of other cellular constituents. The Heinz body anemias appear to represent an acceleration of the normal processes of red cell aging.