The processes leading to red cell destruction in oxidant-induced hemolytic disease are not yet fully known. Oxidant damage to hemoglobin per se may be insufficient to explain the process, and the involvement of membrane damage has been suggested. We now report that at least one crucial membrane function-exclusion of calcium-is disrupted by the potent oxidant phenylhydrazine. Phenylhydrazine, both in vitro and when administered to mice in hemolytic doses, causes profound inhibition of red cell calcium ATPase. Coincident with this, red cell calcium content increases very rapidly in mice given phenylhydrazine. These observations suggest that disordered red cell calcium homeostasis may be an important element in oxidant-induced red cell destruction.

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