Harris R N, Doroshow J H
Biochem Biophys Res Commun. 1985 Jul 31;130(2):739-45. doi: 10.1016/0006-291x(85)90478-4.
This study investigated the effect of doxorubicin-related oxygen radical formation on Ca2+ uptake by rat heart sarcoplasmic reticulum vesicles. Enzymatic activation of doxorubicin by cardiac NADH dehydrogenase produced a dose-related inhibition of Ca2+ uptake that was enzyme- and cofactor-dependent and that was inhibited by catalase, various hydroxyl radical scavengers, and the iron chelator deferoxamine. Furthermore, inhibition of Ca2+ uptake paralleled the production of the hydroxyl radical by NADH dehydrogenase after doxorubicin treatment. These results suggest that doxorubicin-stimulated reactive oxygen metabolism can alter Ca2+ transport by cardiac sarcoplasmic reticulum and may represent one pathway involved in the cardiac toxicity of this potent antineoplastic agent.
本研究调查了阿霉素相关的氧自由基形成对大鼠心脏肌浆网囊泡摄取Ca2+的影响。心脏NADH脱氢酶对阿霉素的酶促激活产生了与剂量相关的Ca2+摄取抑制作用，该抑制作用依赖于酶和辅因子，并被过氧化氢酶、各种羟自由基清除剂和铁螯合剂去铁胺所抑制。此外，阿霉素处理后，Ca2+摄取的抑制与NADH脱氢酶产生的羟自由基平行。这些结果表明，阿霉素刺激的活性氧代谢可改变心脏肌浆网的Ca2+转运，这可能是该强效抗肿瘤药物心脏毒性的一条途径。
