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Antioxidative and neuroprotective activity of alpha-lipoic acid derivatives: spin resonance analyses

Research Project

Project/Area Number 15K10515
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionOita University

Principal Investigator

Tokumaru Osamu  大分大学, 福祉健康科学部, 教授 (40360151)

Co-Investigator(Kenkyū-buntansha) 北野 敬明  大分大学, 医学部, 教授 (20211196)
新宮 千尋  大分大学, 医学部, 准教授 (30295191)
松本 重清  大分大学, 医学部, 准教授 (90274761)
江島 伸興  京都大学, 高大接続・入試センター, 特定教授 (20203630)
西田 育弘  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 生理学, 教授 (90172668)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords抗酸化作用 / フリーラジカル消去作用 / 水溶性αリポ酸誘導体 / 電子スピン共鳴法 / 質量分析イメージング / 高エネルギーリン酸 / NMRメタボロミクス / 抗酸化能 / スピン共鳴解析 / フリーラジカル消去能 / 核磁気共鳴法 / フリーラジカル / ラジカル消去能
Outline of Final Research Achievements

We synthesized α-lipoic acid derivatives which are shown to have antioxidative and anti-inflammatory activity. Using electron spin resonance spectrometry (ESR), we demonstrated that α-lipoic acid derivatives directly scavenged multiple kinds of free radicals in a dose-dependent manner. It is speculated that antioxidative activity of α-lipoic acid derivatives may be attributable to their direct scavenging activity against multiple free radical species. We have also developed an experimental protocol for mass spectroscopic imaging of high-energy phosphates (ATP, ADP, AMP) in mice brain. The present project did not accomplish application of such imaging technique to an evaluation of neuroprotective effect of α-lipoic acid derivatives.

Academic Significance and Societal Importance of the Research Achievements

αリポ酸は活性酸素種や酸化ストレスによる種々の病態における治療効果が期待されてきた。その抗酸化作用の機序はフリーラジカル消去能にあるといわれてきたが,どのフリーラジカルを直接消去するのか,用量依存性はあるのか等の詳細は不明であった。本課題はその機序の一端を明らかにしたことに学術的意義がある。
αリポ酸誘導体の作用機序が解明され,より効果の高い誘導体が選別できれば、比較的早期に臨床応用が期待できる。脳梗塞の血栓溶解療法の補助療法や,心肺停止蘇生後患者,脳神経外科手術患者,人工心肺使用患者など脳虚血の可能性の高い患者への予防的投与など,臨床応用への可能性を探ることに,本研究の社会的意義がある。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] University of Auckland(New Zealand)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors2019

    • Author(s)
      Umeda Ryohei、Takanari Hiroki、Ogata Kazue、Matsumoto Shigekiyo、Kitano Takaaki、Ono Katsushige、Tokumaru Osamu
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 64 Issue: 1 Pages: 20-26

    • DOI

      10.3164/jcbn.18-48

    • NAID

      130007542260

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dose-dependency of multiple free radical-scavenging activity of edaravone2018

    • Author(s)
      Tokumaru Osamu、Shuto Yachiko、Ogata Kazue、Kamibayashi Masato、Bacal Kira、Takei Hidehiro、Yokoi Isao、Kitano Takaaki
    • Journal Title

      Journal of Surgical Research

      Volume: 228 Pages: 147-153

    • DOI

      10.1016/j.jss.2018.03.020

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Changes in correlations of energy status among cerebral regions after high +Gz acceleration2018

    • Author(s)
      Tokumaru O, Goto M, Abe S, Hiruma M, Maruyama S, Kemuriyama T, Ogata K, Kitano T, Nishida Y
    • Organizer
      89th Annual Scientific Meeting of Aerospace Medical Association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dose-response relationship of free radical scavenging activity of dexmedetomidine2018

    • Author(s)
      Tokumaru O, Yoshida K, Ogata K, Takanari H, Kitano T
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The dynamics of energy metabolism in brain after ischemia/reperfusion injury: an animal model study using high-Gz acceleration2017

    • Author(s)
      Tokumaru O, Abe S, Moeha Goto M, Tandai-Hiruma M, Kemuriyama T, Maruyama S, Kanamaru Y, Ogata K, Nishida Y
    • Organizer
      28th International Symposium on Cerebral Blood Flow, Metabolism and Function
    • Place of Presentation
      ベルリン自由大学(ベルリン市・ドイツ連邦共和国)
    • Year and Date
      2017-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The dynamics of blood circulation and high energy phosphates in ischemia/reperfusion injury caused by applying high gravity in mouse brain2017

    • Author(s)
      Abe S, Kumatani J, Nagai S, Minamikawa Y, Tokumaru O, Hiruma M, Kemuriyama T, Maruyama S, Ono K, Nishida Y
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県・浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] The dynamics of energy metabolism in brain after ischemia/reperfusion injury: an animal model study using high-Gz acceleration2017

    • Author(s)
      Osamu Tokumaru, Sakurako Abe, Moeha Goto, Megumi Tandai-Hiruma,
    • Organizer
      28th International Symposium on Cerebral Blood Flow, Metabolism and Function
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Direct observation of ascorbyl free radicals (vitamin C radicals) in blood of perioperative animals2017

    • Author(s)
      Osamu Tokumaru, Shigekiyo Matsumoto, Takayuki Mizoguchi, Takayuki Kawashima, Kazue Ogata, Shinji Miyamoto, Takaaki Kitano
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 周術期の血液から検出されるアスコルビン酸フリーラジカルについて2016

    • Author(s)
      徳丸治,松本重清,岡本啓太郎,溝口貴之,尾方和枝.北野敬明
    • Organizer
      第69回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター会議棟(宮城県・仙台市)
    • Year and Date
      2016-08-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳虚血下でのマウス脳の血液循環と高エネルギーリン酸の変化2016

    • Author(s)
      後藤萌葉, 志村冬華, 徳丸治, 丸山聡, 晝間恵, 煙山健仁, 尾方和枝, 花田礼子, 西田育弘
    • Organizer
      第93回日本生理学会
    • Place of Presentation
      札幌コンベンションセンター (札幌市白石区東札幌6条1丁目1-1)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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