Winterbourn C C, Gutteridge J M, Halliwell B
J Free Radic Biol Med. 1985;1(1):43-9. doi: 10.1016/0748-5514(85)90028-5.
Doxorubicin semiquinone, produced by reduction of doxorubicin with xanthine oxidase or ferredoxin reductase, reacted with H2O2 to cause deoxyribose oxidation that was catalysed by sub-micromolar concentrations of complexed iron. Both the mechanism of deoxyribose oxidation and the yield of oxidation products depended on the chelator. With EDTA or diethylenetriamine penta-acetic acid (DTPA), the reactive species behaved like free . OH. However, when ADP or no chelator was present, oxidation of deoxyribose was inhibited by mannitol but not benzoate or formate and was apparently not due to free . OH. Doxorubicin semiquinone and H2O2 caused peroxidation of phospholipid liposomes when ADP or no chelator was present, but not in the presence of EDTA or DTPA. Lipid peroxidation was iron dependent over a 0.1 to 1 microM range and was maximal with a pO2 of approximately 1.5 mm Hg, when the inhibitory effect of O2 on initiation is balanced by its stimulatory effects on propagation. The results imply that H2O2 and the doxorubicin semiquinone at low iron and O2 concentrations are very effective at initiating lipid peroxidation.
阿霉素半醌由阿霉素经黄嘌呤氧化酶或铁氧化还原蛋白还原酶还原产生，它与过氧化氢反应导致脱氧核糖氧化，此反应由亚微摩尔浓度的络合铁催化。脱氧核糖氧化的机制及氧化产物的产率均取决于螯合剂。使用乙二胺四乙酸（EDTA）或二乙烯三胺五乙酸（DTPA）时，反应性物种的行为类似于游离的·OH。然而，当存在二磷酸腺苷（ADP）或不存在螯合剂时，脱氧核糖的氧化受到甘露醇抑制，但不受苯甲酸盐或甲酸盐抑制，且显然不是由游离的·OH引起的。当存在ADP或不存在螯合剂时，阿霉素半醌和过氧化氢会导致磷脂脂质体发生过氧化反应，但在EDTA或DTPA存在时则不会。脂质过氧化在0.1至1微摩尔范围内依赖于铁，在约1.5毫米汞柱的氧分压下达到最大值，此时氧气对引发的抑制作用与其对传播的刺激作用达到平衡。结果表明，在低铁和低氧浓度下，过氧化氢和阿霉素半醌在引发脂质过氧化方面非常有效。
