Sagone A L, Burton G M
Am J Hematol. 1979;7(2):97-106. doi: 10.1002/ajh.2830070202.
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.
在无细胞系统中，阿霉素可诱导产生氧自由基。我们之前已经表明，阿霉素可在人红细胞中产生过氧化物。卡氮芥通过抑制谷胱甘肽还原酶，干扰红细胞降解过氧化物的主要途径。在本研究中，我们观察了这些药物与正常及异常红细胞之间的相互作用。在葡萄糖-6-磷酸脱氢酶（G6PD）缺乏的红细胞中，阿霉素造成了显著的氧化应激，这可通过磷酸己糖旁路（HMPS）活性、过氧化氢（H2O2）生成及谷胱甘肽耗竭得以证明。在相似的摩尔浓度下，阿霉素比乙酰苯肼是更强的氧化剂。经卡氮芥处理的正常红细胞对氧化应激的敏感性增强，这可通过在与阿霉素共同孵育期间对H2O2缺乏HMPS反应及谷胱甘肽耗竭得以证明。经卡氮芥处理的红细胞的HMPS旁路是完整的，这可通过它们对亚甲蓝刺激的近乎正常反应得以显示。这些关于卡氮芥的研究还证明了H2O2不能直接与NADPH反应。总之，阿霉素对G6PD缺乏的红细胞造成了强烈的氧化应激。卡氮芥促进正常红细胞对氧化应激的易感性增强，并且卡氮芥可作为一种探针来确定药物与HMPS之间的相互作用。这些研究增加了越来越多的证据，这些证据假定氧自由基在阿霉素的治疗和/或作用中具有重要性。
