Vile G F, Winterbourn C C
Department of Pathology, Christchurch School of Medicine, Christchurch Hospital, New Zealand.
Cancer Chemother Pharmacol. 1989;24(2):105-8. doi: 10.1007/BF00263129.
Rat-liver microsomes and NADPH could reduce Adriamycin, epirubicin and daunorubicin to their free radical forms, which enhanced peroxidation of microsomal lipids less than 2-fold in air but 3- to 5-fold at a pO2 of 4 mmHg. Mitoxantrone was not reduced by microsomes and had no effect on microsomal peroxidation. Daunorubicin caused more lipid peroxidation than similar concentrations of either Adriamycin or epirubicin, which were equally efficient. In each case peroxidation was iron-dependent and could be catalysed by ferritin. The antioxidants beta-carotene and alpha-tocopherol inhibited lipid peroxidation at low or high pO2. The dose-for-dose difference in the cardiotoxicity of epirubicin compared with Adriamycin is not explained by its effect on microsomal lipid peroxidation. However, the lower incidence of cardiotoxicity with mitoxantrone may be a consequence of its inability to form free radical species and promote lipid peroxidation.
大鼠肝脏微粒体和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）可将阿霉素、表柔比星和柔红霉素还原为自由基形式，在空气中这种自由基形式使微粒体脂质过氧化增强不到2倍，但在4 mmHg的氧分压下则增强3至5倍。米托蒽醌不能被微粒体还原，且对微粒体过氧化没有影响。柔红霉素比相同浓度的阿霉素或表柔比星引起更多的脂质过氧化，而后两者的作用效果相当。在每种情况下，过氧化均依赖铁，且可被铁蛋白催化。抗氧化剂β-胡萝卜素和α-生育酚在低氧或高氧分压下均能抑制脂质过氧化。表柔比星与阿霉素相比，其心脏毒性在剂量上的差异并不能通过其对微粒体脂质过氧化的影响来解释。然而，米托蒽醌心脏毒性发生率较低可能是由于其无法形成自由基并促进脂质过氧化的结果。
