Dose-dependency of multiple free radical-scavenging activity of edaravone
Dose-dependency of multiple free radical-scavenging activity of edaravone
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DOI：
10.1016/j.jss.2018.03.020
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发表时间：
2018-08-01
影响因子：
2.2
通讯作者：
Kitano, Takaaki
中科院分区：
文献类型：
--
作者：
Tokumaru, Osamu;Shuto, Yachiko;Kitano, Takaaki
背景：依达拉奉是一种有效的自由基清除剂，已在临床上应用。然而，关于其对多种自由基的剂量-反应关系的数据仍然稀少。本研究的目的是证明依达拉奉对多种自由基种类的直接清除活性的剂量依赖性。材料和方法：使用自旋捕获法通过电子自旋共振光谱评价依达拉奉对6种自由基种类的自由基清除活性。依达拉奉以剂量依赖性方式清除下列自由基，反应速率常数（k（依达拉奉））或50%抑制浓度（IC 50），如所示：羟基自由基（k（依达拉奉）= 5.2 x 10（10）M-1 s（-1）），超氧阴离子（k（依达拉奉）/ k（G-CYPMPO）= 0.63），叔丁基过氧自由基（k（依达拉奉）/k（G-CYPMPO）= 8.8），抗坏血酸自由基（IC 50 = 0.17 +/- 0.06 mM），2，2-二苯基-1-苦肼基（DPPH，IC 50 = 4.7 +/- 0.3 μ M）和一氧化氮（k（依达拉奉）= 7.0 × 10（3）M-1 s（-1））。结论：依达拉奉对多种自由基的清除活性具有明显的剂量依赖性。据推测，依达拉奉通过剂量依赖性地清除手术中氧化应激连锁反应沿着的多种自由基，发挥抗氧化剂作用。(C)2018爱思唯尔公司All rights reserved.
Background: Edaravone is a powerful free radical scavenger that is in clinical use. However, data concerning its dose-response relationship against multiple free radicals remain sparse. The purpose of the present study was to demonstrate the dose-dependency of direct scavenging activity of edaravone against multiple free radical species.Materials and methods: Free radical-scavenging activities of edaravone against six free radical species were evaluated by electron spin resonance spectroscopy using spin-trapping method.Results: Edaravone scavenged the following free radicals in dose-dependent manners with reaction rate constants (k(edaravone)) or 50% inhibitory concentration (IC50) as indicated: hydroxyl radical (k(edaravone) = 5.2 x 10(10) M-1 s(-1)), superoxide anion (k(edaravone)/ k(G-CYPMPO) = 0.63), tert-butyl peroxyl radical (k(edaravone)/k(G-CYPMPO) = 8.8), ascorbyl free radical (IC50 = 0.17 +/- 0.06 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50= 4.7 +/- 0.3 mu M), and nitric oxide (k(edaravone) = 7.0 x 10(3) M-1 s(-1)).Conclusions: The dose-dependent scavenging activities of edaravone against multiple free radical species were clearly illustrated. It is speculated that edaravone acts as antioxidant by dose-dependently scavenging multiple free radical species along the chain reactions of oxidative stress in surgery. (C) 2018 Elsevier Inc. All rights reserved.