Sterrenberg L, Julicher R H, Bast A, Noordhoek J
Toxicol Lett. 1984 Aug;22(2):153-9. doi: 10.1016/0378-4274(84)90059-6.
The antitumor drug, adriamycin, enhances NADPH-dependent lipid peroxidation in liver microsomes via the formation of superoxide anion radicals (O2) and hydrogen peroxide (H2O2). In the presence of metal ions additional reactive species are generated, causing stimulation of lipid peroxidation. However, in this study it was found that the stimulation of NADPH-dependent lipid peroxidation by adriamycin was not only affected by the production of O2 and H2O2. Adriamycin also enhances the catalysis by metal ions of the formation of those reactive oxygen species which initiate peroxidation. This was inferred from the fact that adriamycin stimulated malondialdehyde production at low ferrous ion concentrations, whereas at high ferrous ion concentrations no stimulation was found. Additional evidence was found in experiments in which the enzymic redox cycle of adriamycin in microsomes was abolished by heat-inactivation of the microsomes, and O2 and H2O2 were only produced with xanthine and xanthine oxidase. In this case in the presence of ferrous ions, adriamycin stimulated lipid peroxidation.
抗肿瘤药物阿霉素通过超氧阴离子自由基（O₂）和过氧化氢（H₂O₂）的形成，增强肝微粒体中依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的脂质过氧化作用。在金属离子存在的情况下，会产生额外的活性物质，从而刺激脂质过氧化。然而，在本研究中发现，阿霉素对依赖NADPH的脂质过氧化的刺激作用不仅受到O₂和H₂O₂产生的影响。阿霉素还增强了金属离子对引发过氧化的活性氧物种形成的催化作用。这是从以下事实推断出来的：阿霉素在低亚铁离子浓度下刺激丙二醛生成，而在高铁离子浓度下未发现刺激作用。在通过微粒体热失活消除微粒体中阿霉素的酶促氧化还原循环，且仅用黄嘌呤和黄嘌呤氧化酶产生O₂和H₂O₂的实验中发现了额外的证据。在这种情况下，在亚铁离子存在下，阿霉素刺激脂质过氧化。
