The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes.
In cell free systems Adriamycin induces oxygen radicals. We have shown previously that Adriamycin generates peroxide in human erythrocytes. BCNU, by inhibiting glutathione reductase, interferes with the major erythrocyte pathway to degrade peroxide. In this investigation we looked at interactions of these drugs with normal and abnormal erythrocytes. In G6PD-deficient erythrocytes Adriamycin posed a significant oxidant stress as demonstrated by hexose monophosphate shunt (HMPS) activity, hydrogen peroxide (H2O2) production, and glutathione depletion. At similar molar concentrations Adriamycin was a stronger oxidant than acetylphenylhydrazine. BCNU=treated normal erythrocytes showed an enhanced susceptibility to oxidant stress as demonstrated by a lack of HMPS response to H2O2 and glutathione depletion during incubations with Adriamycin. The HMPS shunt of BCNU treated RBC was intact as shown by their nearly normal response to methylene blue stimulation. These BCNU studies also demonstrated the inability of H2O2 to react directly with NADPH. In conclusion Adriamycin poses a potent oxident stress to G6PD-deficient erythrocytes. BCNU promotes enhanced susceptibility of normal RBC to oxidant stress and BCNU can act as a probe to define drug interactions with the HMPS. These studies add to a growing body of evidence postulating the importance of oxygen radicals in the therapeutic and/or effects of Adriamycin.
D002330:Carmustine / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D005561:Formates / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D005978:Glutathione / Q000097:blood; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006601:Hexoses / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D010084:Oxidation-Reduction; D013997:Time Factors
D005561:Formates; D006601:Hexoses; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D005980:Glutathione Reductase; D005978:Glutathione; D002330:Carmustine