Effects by doxorubicin on the myocardium are mediated by oxygen free radicals.
Effects by doxorubicin on the myocardium are mediated by oxygen free radicals.
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DOI：
10.1016/s0024-3205(00)00990-5
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发表时间：
2001-01
期刊：
影响因子：
6.1
通讯作者：
Mei Feng Xu;Pak Lai Tang;Zhong Ming Qian;Muhammad Ashraf
中科院分区：
文献类型：
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作者：
Mei Feng Xu;Pak Lai Tang;Zhong Ming Qian;Muhammad Ashraf
我们假设阿霉素（DOX）通过氧自由基诱导心肌毒性。本研究旨在检查成年大鼠和培养的新生肌细胞中 DOX 产生的氧自由基对细胞膜的改变。我们的结果表明，DOX 1) 降低细胞膜中的 β-肾上腺素受体 (BAR) 密度，2) 增加培养的新生大鼠肌细胞的膜通透性，3) 改变肌原纤维和质膜下肌动蛋白网络的超微结构。这些效果可以通过外源过氧化氢重现。抗氧化剂褪黑激素（MLT）以浓度依赖性方式抑制酶渗漏和过氧化。结论是DOX通过脂质过氧化诱导心脏毒性，而褪黑激素是对抗DOX产生的活性氧中间体的有效抗氧化剂。
We hypothesized that doxorubicin (DOX) induces cardiotoxicity of myocardium via oxygen radicals. The present study is aimed at examining the membrane alterations by oxygen radicals generated by DOX in adult rats and cultured neonatal myocytes. Our results showed that DOX 1) decreased β-adrenoceptor (BAR) density in the cell membrane, 2) increased the membrane permeability of cultured neonatal rat myocytes and 3) altered the ultrastructure of myofibrils and subplasmalemmal actin networks. These effects were reproducible by exogenous hydrogen peroxide. The antioxidant melatonin (MLT) inhibited enzyme leakage and peroxidation in a concentration-dependent manner. It is concluded that DOX induces cardiotoxicity through lipid peroxidation and melatonin is an effective antioxidant against the reactive oxygen intermediates generated by DOX.