Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action
Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action
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DOI：
10.1161/01.cir.100.7.690
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发表时间：
1999-08-17
期刊：
影响因子：
37.8
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Ide, T;Tsutsui, H;Takeshita, A
氧化应激在缺血性心脏病和心力衰竭的病理生理学中起重要作用，抗氧化剂可能对这些患者的治疗有益。本研究旨在探讨胺碘酮对氧自由基的清除作用及其对氧自由基介导的心肌细胞损伤的保护作用。OH）在H_2O_2（10 mmol/L）和Fe ~（3+）-次氮基三乙酸盐（20 μ mol/L）存在下，通过电子顺磁共振光谱结合自旋捕获剂5，5-二甲基吡咯啉-N-氧化物（DMPO）监测。胺碘酮以剂量依赖性方式（0.1至100 μ mol/L）降低DMPO-OH信号的强度，而其他抗心律失常药物如丙吡胺和阿替洛尔则无此作用。此外，胺碘酮（10 μ mol/L）保护完整的成年犬心肌细胞免受OH介导的心肌细胞损伤，通过细胞在体外暴露于H2 O2和Fe 3+期间从杆状到不可逆的过度挛缩状态的形态学变化程度来评估。结论胺碘酮可以通过直接清除氧自由基来保护心肌细胞免受氧化应激介导的损伤。胺碘酮的抗氧化作用可能有助于该药治疗缺血性心脏病和充血性心力衰竭患者的有益作用。
Background-Oxidative stress plays an important role in the pathophysiology of ischemic heart disease and heart failure, and antioxidants might be beneficial in the treatment of these patients. This study was performed to determine the scavenging effects of amiodarone on oxygen free radicals and its protective effects against oxygen radical-mediated injury in cardiac myocytes.Methods and Results-The formation of the radical spin adduct with hydroxy radical (. OH) in the presence of H2O2 (10 mmol/L) and Fe3+-nitrilotriacetate (20 mu mol/L) was monitored by electron paramagnetic resonance spectroscopy combined with a spin trapping agent, 5,5-dimethyl pyrroline-N-oxide (DMPO). Amiodarone decreased the intensity of the DMPO-OH signals in a dose-dependent manner (0.1 to 100 mu mol/L), whereas other antiarrhythmia drugs such as disopyramide and atenolol had no such effects. Furthermore, amiodarone (10 mu mol/L) protected intact adult canine cardiac myocytes against OH-mediated myocyte injury, as assessed by the degree of morphological change from rod shape to the irreversible hypercontracture state during the exposure of cells to H2O2 and Fe3+ in vitro,Conclusions-Amiodarone can protect cardiac myocytes against oxidative stress-mediated injury by directly scavenging oxygen free radicals. Antioxidant action of amiodarone might potentially contribute to the beneficial effects of this drug in the treatment of patients with ischemic heart disease and congestive heart failure.