Superoxide anion as a mediator of drug-induced oxidative hemolysis

The superoxide dismutase inhibitor diethyldithiocarbamate (DDC) was utilized to study the toxic effect of 1,4-naphthoquinone 2-sulfonate (NQ), a structural analog of the hemolytic drug, menadione, on red cells. NQ was shown to react with hemoglobin and result in the generation of superoxide anion (O2-). Red cells treated with NQ were found to undergo a gradual disappearance of their oxyhemoglobin and also hemolyze. Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ. Superoxide dismutase-inhibited red cells were also found to undergo a slow autohemolysis in the absence of NQ. No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC. Ghosts prepared from superoxide dismutase-inhibited red cells exposed to NQ were found to retain a green hemoglobin-derived pigment.