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Neuronal Death and Neuroprotection

開催日 2014/9/11
時間 17:00 - 18:00
会場 Room I(311+312)
Chairperson(s) 木村 英雄 / Hideo Kimura ((独)国立精神・神経医療研究センター 神経研究所 神経薬理研究部 / Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Japan)
小笠原 裕樹 / Yuki Ogasawara (明治薬科大学 分析化学教室 / Department of Analytical Biochemistry, Meiji Pharmaceutical University, Japan)

Edaravone, a radical scavenger, may behave as a prooxidant

  • O1-I-5-4
  • 徳丸 治 / Osamu Tokumaru:1 首藤 八千子 / Yachiko Shuto:1 尾方 和枝 / Kazue Ogata:1 北野 敬明 / Takaaki Kitano:2 横井 功 / Isao Yokoi:1 
  • 1:大分大・医・神経生理 / Dept Neurophysiol, Oita Univ Fac Med, Oita, Japan 2:大分大・医・医学教育 / Med Edu Cntr, Oita Univ Fac Med, Oita, Japan 

It is well known that edaravone is a powerful free radical scavenger, and it has been applied in clinical settings for the treatment of cerebral infarction. But data concerning its direct radical scavenging activity are still sparse as far as the authors surveyed. Recently the authors directly evaluated dose-response relationship of edaravone against multiple free radicals by electron spin resonance spectroscopy using the spin trapping method. Edaravone scavenged the following multiple free radicals with significant IC50(p < 0.01); hydroxyl radical 0.4 mM (produced by UV irradiation to diluted H2O2 and trapped by CYPMPO), superoxide anion 4 mM, t-butyl peroxyl radical 0.3 mM, ascorbyl free radical 2 mM, nitric oxide 40 μM, DPPH radical 5 μM (Tokumaru et al., 91st PSJ Annual Meeting, 2014). In an attempt to further evaluate the radical scavenging activity with different radical producing /spin trapping systems, the authors have found prooxidant-like activity of edaravone. When hydroxyl radicals were produced by UV irradiation to diluted H2O2 and trapped by DMPO, one of the most frequently used spin trap, not only hydroxyl radicals but also methyl radicals were detected and both radicals continued to increase after the initial radical production, and reached plateau in approximately 45 min. The slope and plateau level increased in a dose-dependent manner (10 μM - 1 mM). It might be possible that methyl radicals released from edaravone by hydroxyl radicals' attack re-produced hydroxyl radicals in a chain reaction. This is the first to report its possibility of prooxidant-like activity in a certain conditions.

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