Neuroprotective effects of acetyl-L-carnitine againstischemia-reperfusion injury: a spin resonance study

• Project/Area Number: 24592304
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Oita University
• Principal Investigator: TOKUMARU Osamu 大分大学, 医学部, 准教授 (40360151)
• Co-Investigator(Kenkyū-buntansha): KITANO Takaaki 大分大学, 医学部, 教授 (20211196) ; YOKOI Isao 大分大学, 医学部, 教授 (80150366) ; KOGA Hironori 大分大学, 医学部, 助教 (50468013)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アセチル-L-カルニチン / 脳保護 / 核磁気共鳴法 / 電子スピン共鳴法 / フリーラジカル / 抗酸化能 / ラジカル消去能 / 高エネルギーリン酸 / 脳保護作用 / カルニチン / 虚血再潅流傷害 / スピントラップ法 / 虚血再灌流傷害 / スピントラップ / 脳虚血 / クレアチンリン酸 / ATP / 病態生理学

Outline of Final Research Achievements

Neuroprotective effect of acetyl-L-carnitine (ALCAR) on rat brain slices after ischemia/reperfusion injury was investigated by 31P-NMR and ESR spectroscopy. Energetically, ALCAR was neuroprotective in normal brain slices. ALCAR demonstrated antioxidative activity against some free radical species, but it also showed rather prooxidative activity against others at higher concentrations. Those findings suggest that ALCAR acts as energy substrate and antioxidant in protecting brain tissue from ischemia/reperfusion injury, but may act as prooxidant at higher concentration.

Research Products

• [Journal Article] Hypoperfusion-reperfusion injury and reactive oxygen species: spin resonance analyses (2015)
  • Author(s): Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Journal Title: J Physiol Sci Volume: 65
• [Journal Article] Multiple free-radical scavenging activity of alpha lipoic acid derivatives: an ESR study (2015)
  • Author(s): Wakayama A, Mizutani Y, Shimada M, Tokumaru O, Ogata K, Uchino T, Kitano T, Yokoi I
  • Journal Title: J Physiol Sci Volume: 65
• [Journal Article] Spectrum of dose-response relationship for radical scavenging activity of edaravone (2014)
  • Author(s): Tokumaru O, Shuto Y, Ogata K, Yokoi I
  • Journal Title: J Physiol Sci. Volume: 64
• [Journal Article] Neuroprotective effect of water-soluble vitamin E derivatives as radical scavengers/antioxidants (2014)
  • Author(s): Suezumi K., Yamada K., Tokumaru O., Ogata K., Kitano T., Yokoi I
  • Journal Title: J Physiol Sci. Volume: 64
• [Journal Article] 虚血－再灌流負荷に対するラットの脳エネルギー代謝の変化：31P-NMRによる経時的検討 (2013)
  • Author(s): 徳丸治，北野敬明，横井功
  • Journal Title: 日本生理学会雑誌 Volume: 75(5), Pt2 Pages: 31-33
• [Journal Article] Recovery of energy metabolism of rat brain after ischemia-reperfusion injury: a 31P-NMR study (2013)
  • Author(s): Tokumaru O, Kitano T, Yokoi I
  • Journal Title: J Physiol Sci Volume: 63
• [Journal Article] Neuroprotective effects of a water-soluble α-lipoic acid derivative, DM-His.Zn, on rat brain tissue after ischemia-reperfusion injury : spin resonance analyses study (2013)
  • Author(s): Mizutani Y,Shimada M, Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Journal Title: J Physiol Sci Volume: 63
• [Journal Article] Neuroprotective effects of acetyl-L-carnitine on rat brain slices after ischemia-reperfusion injury: spin resonance analyses study (2013)
  • Author(s): Shimada M, Mizutani Y, Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Journal Title: J Physiol Sci Volume: 63
• [Journal Article] Age-Specific Sex-Related Differences in Infections: A Statistical Analysis of National Surveillance Data in Japan (2012)
  • Author(s): Eshima, N, Tokumaru, O, Hara, S, Bacal, K, Korematsu, S, Karukaya, S, Uruma, K, Okabe, N, Matsuishi, T
  • Journal Title: PLoS ONE Volume: 7, 7, e442261 Issue: 7 Pages: e42261-e42261
  • DOI: 10.1371/journal.pone.0042261
  • Peer Reviewed
• [Presentation] Evaluation of scavenging activity against multiple species of free radicals by electron spin resonance spectroscopy (2015)
  • Author(s): Tokumaru O, Ogata K, Kitano T, Yokoi I.
  • Organizer: XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function
  • Place of Presentation: Vancouver Convention Centre (Vancouver, Canada)
  • Year and Date: 2015-06-27 – 2015-06-30
• [Presentation] Hypoperfusion-reperfusion injury and reactive oxygen species: spin resonance analyses (2015)
  • Author(s): Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場・展示場（神戸）
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited
• [Presentation] Multiple free-radical scavenging activity of alpha lipoic acid derivatives: an ESR study (2015)
  • Author(s): Wakayama A, Mizutani Y, Shimada M, Tokumaru O, Ogata K, Uchino T, Kitano T, Yokoi I
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場・展示場（神戸）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 水溶性αリポ酸誘導体DHL-Tau.Znのラジカル消去能：ESRによる検討 (2014)
  • Author(s): 若山愛海，徳丸治，尾方和枝，内納智子，松本重清，北野敬明，横井功
  • Organizer: 第5回癌・炎症と抗酸化研究会
  • Place of Presentation: 別府湾ロイヤルホテル（大分県日出町）
  • Year and Date: 2014-11-14
• [Presentation] Edaravone, a radical scavenger, may behave as a prooxidant (2014)
  • Author(s): Tokumaru O, Shuto Y, Ogata K, Kitano T, Yokoi I
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Spectrum of dose-response relationship for radical scavenging activity of edaravone (2014)
  • Author(s): Tokumaru O, Shuto Y, Ogata K, Yokoi I
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス（鹿児島市）
• [Presentation] Neuroprotective effect of water-soluble vitamin E derivatives as radical scavengers/antioxidants (2014)
  • Author(s): Suezumi K., Yamada K., Tokumaru O., Ogata K., Kitano T., Yokoi I
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス（鹿児島市）
• [Presentation] Water-soluble α-lipoic acid derivative, DM-His.Zn, scavenges free radicals, inhibits peroxidation, and protects brain tissue from ischemia-reperfusion injury (2013)
  • Author(s): Tokumaru O, Mizutani Y, Shimada M, Ogata K, Kitano T, Yokoi I
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都国際会館（京都市）
• [Presentation] Neuroprotective effects of acetyl-L-carnitine agonist ischemia-reperfusion injury: a spin resonance study (2013)
  • Author(s): Tokumaru O, Shimada M, Mizutani Y, Ogata K, Kitano T, Yokoi I
  • Organizer: IUPS2013（第37回国際生理学会議）
  • Place of Presentation: The International Convention Centre (Birmingham, 英国)
• [Presentation] Recovery of energy metabolism of rat brain after ischemia-reperfusion injury: a 31P-NMR study (2013)
  • Author(s): Tokumaru O, Kitano T, Yokoi I
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Neuroprotective effects of a water-soluble α-lipoic acid derivative, DM-His.Zn, on rat brain tissue after ischemia-reperfusion injury : spin resonance analyses study (2013)
  • Author(s): Mizutani Y,Shimada M, Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Neuroprotective effects of acetyl-L-carnitine on rat brain slices after ischemia-reperfusion injury: spin resonance analyses study (2013)
  • Author(s): Shimada M, Mizutani Y, Tokumaru O, Ogata K, Kitano T, Yokoi I
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Water-soluble α-lipoic acid derivative, DM-His.Zn, scavenges free radicals, inhibits peroxidation, and protects brain tissue from ischemia-reperfusion injury (2013)
  • Author(s): Tokumaru O, Mizutani Y,Shimada M, Ogata K, Kitano T, Yokoi I
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] Neuroprotective effects of acetyl-L-carnitine against ischemia-reperfusion injury: a spin resonance study (2013)
  • Author(s): Tokumaru O, Shimada M, Mizutani Y, Ogata K, Kitano T, Yokoi I
  • Organizer: IUPS 2013（第37回国際生理学会議）
  • Place of Presentation: Birmingham, U.K.
• [Presentation] Neuroprotective effect of CV159 on brain energy metabolism after ischemia-reperfusion injury: a 31P-NMR study (2012)
  • Author(s): Tokumaru O, Kuroki C, Ogata K, Kitano T, Yokoi I
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] 水溶性αリポ酸誘導体DM-His.Znのラジカル除去作用：ESRによる検討
  • Author(s): 徳丸治，北野敬明，横井功
  • Organizer: 第4回癌・炎症とαリポ酸研究会
  • Place of Presentation: 別府湾ロイヤルホテル（大分県日出町）
• [Remarks] 大分大学医学部神経生理学講座ホームページ
  • URL: http://www.med.oita-u.ac.jp/seiri1/