Key result
Adriamycin induced peroxidation of red blood cell constituents and inhibited ATPase, with a greater oxidizing effect observed in G-6-PD deficient erythrocytes.
Why the study?
Does adriamycin induce oxidative damage and alter ion transport in human red blood cells?
Does adriamycin induce oxidative damage and alter ion transport in human red blood cells?
Adriamycin induces oxidative damage and alters ion transport in human red blood cells, particularly in G-6-PD deficient cells, which may serve as a model for its cardiotoxicity.
Positions G-6-PD deficient erythrocytes as cardiotoxicity model; animal data leaves open human relevance.
We have studied the effects of adriamycin (doxorubicin HCl) on human red blood cells. The peroxidizing effect of adriamycin on the thiols of red cell constituents resulted in decreased glutathione stability, and oxidation of hemoglobin and membrane protein components 1, 2, and 3, forming large molecular weight complexes. Membrane lipids were also peroxidized. Adriamycin itself did not inhibit the enzymes of the reductions system (glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase) of the red cells. Because adriamycin has the potential of inhibiting ATPase, including both Na-K-dependent ATPase and ouabain insensitive ATPase, at concentrations not inhibitory to other enzymes, the net sodium content increased, and potassium content decreased after incubation of red cells with adriamycin at high concentrations. The experimental results described with adriamycin may serve as a model for the possible mechanism of cardiotoxicity observed in its clinical use, and also explain the potential hemolyzing effect on red cells. There was greater oxidizing effect on glucose-6-phosphate dehydrogenase (G-6-PD) deficient than on normal erythrocytes. It is suggested that adriamycin be used with caution in individuals with G-6-PD deficient red cells.
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Shinohara et al. (1980) studied Human red blood cells (normal and G-6-PD deficient). Adriamycin (doxorubicin HCl) was evaluated on Effects on red cell constituents including thiols, hemoglobin, membrane proteins, lipids, enzymes, and electrolytes. Adriamycin induced peroxidation of red blood cell constituents and inhibited ATPase, with a greater oxidizing effect observed in G-6-PD deficient erythrocytes.
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