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Investigation on the mechanism of the multiple effects of the inhalation of hydrogen gas for mitigating ischemia reperfusion injury

Research Project

Project/Area Number 16K15599
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionJuntendo University (2017-2018)
Nippon Medical School (2016)

Principal Investigator

Ohta Shigeo  順天堂大学, 医学部, 客員教授 (00125832)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords水素ガス / 分子状水素 / 虚血再灌流障害 / 脂質メディエーター / 転写因子NFAT / 脳梗塞 / 心肺停止後蘇生 / 水素 / 虚血再灌流 / 実験外科学
Outline of Final Research Achievements

We have previously revealed that inhalation of hydrogen gas mitigated oxidative stress injury including ischemia reperfusion by animal model experiments. In this study, we investigated the efficient method for the inhalation of hydrogen gas by using a model animal. Then, we showed the efficacies of the inhalation of hydrogen gas for patients with cerebral infarction and cardiac arrest by clinical studies. Moreover, we revealed the molecular mechanism by which hydrogen exhibits the multiple functions: hydrogen modifies the free radical chain reaction to generate the oxidized phospholipids as a signal mediator. The signal mediator suppressed the calcium signaling, and suppressed the activation of a transcription factor NFAT. Since NFAT transcribes many factors, hydrogen can exert multiple functions for the mitigation of ischemia reperfusion injury.

Academic Significance and Societal Importance of the Research Achievements

水素ガス吸入による虚血再灌流障害を実際の治療に用いられるようにするには、臨床試験によって、患者への有効性を示すことが必要である。本研究によって、水素ガス吸入は、脳梗塞患者と心肺停止後蘇生患者の改善に対して有効であることを示唆した。水素ガス吸入治療は、厚生労働省から先進医療Bとして承認され、研究と同時に治療にも用いられている。薬事承認にあたっては、分子機構を解明することが必要である。本研究では、水素が多機能を発揮する分子機作を明らかにした。また、学術的にも、新たしいシグナル伝達機構の解明に寄与した。

Report

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

    (30 results)

All 2019 2018 2017 2016 Other

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 12 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Acute Supplementation with Molecular Hydrogen Benefits Submaximal Exercise Indices. Randomized, Double-Blinded, Placebo-Controlled Crossover Pilot Study2019

    • Author(s)
      LeBaron TW, Larson AJ, Ohta S, Mikami T, Barlow J, Bulloch J, DeBeliso M
    • Journal Title

      J Lifestyle Med.

      Volume: 9 Issue: 1 Pages: 36-43

    • DOI

      10.15280/jlm.2019.9.1.36

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.2019

    • Author(s)
      Ohsawa Y, Hagiwara H, Nishimatsu SI, Hirakawa A, Kamimura N, Ohtsubo H, Fukai Y, Murakami T, Koga Y, Goto YI, Ohta S, Sunada Y; KN01 Study Group.
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: 90 Issue: 5 Pages: 529-536

    • DOI

      10.1136/jnnp-2018-317964

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute immobilization stress following contextual fear conditioning reduces fear memory: timing is essential2019

    • Author(s)
      Akemi Uwaya, Hyunjin Lee, Jonghyuk Park, Hosung Lee, Junko Muto, Sanae Nakajima, Shigeo Ohta,Toshio Mikami
    • Journal Title

      Behavioral and Brain functions

      Volume: 12 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s12993-016-0092-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Molecular Hydrogen Assessed by an Animal Model and Randamized Clinical Study on Mild Cognitive Impairment.2018

    • Author(s)
      Nishimaki K., Asada T.,Ohsawa I.,Nakajima E.,Ikejima C.,Yokota T.,Kamimura N.,Ohta S.
    • Journal Title

      Current Alzheimmer Research.

      Volume: 15 Issue: 5 Pages: 482-492

    • DOI

      10.2174/1567205014666171106145017

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pilot Study on Therapeutic Inhalation of Hydrogen Gas for Improving Patients with Alzheimer’s Disease Assessed by Cognitive Subscale Scores and Magnetic Resonance Diffusion Tensor Imaging2018

    • Author(s)
      Ono H, Nishijima Y, Sakamoto M, Horikosi T, Tamaki M, Oishi W, Naitoh Y, Futaki T, shii S, Suzuki K, Kurihara H and Ohta S
    • Journal Title

      International Journal of Alzheimers & Neurological Disorders

      Volume: 1 Pages: 1-11

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.2017

    • Author(s)
      Ono H, Nishijima Y, Ohta S, Sakamoto M, Kinone K, Horikosi T, Tamaki M, Takeshita H, Futatuki T, Ohishi W, Ishiguro T, Okamoto S, Ishii S, Takanami H.
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 26 Issue: 11 Pages: 2587-2594

    • DOI

      10.1016/j.jstrokecerebrovasdis.2017.06.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184-16193 poly-cytosine tract), which confer resistance to cisplatin.2017

    • Author(s)
      Amo T, Kamimura N, Asano H, Asoh S, Ohta S.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 46240-46240

    • DOI

      10.1038/srep46240

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blue light-induced oxidative stress in live skin2017

    • Author(s)
      Nakashima Y, Wolf AM, Ohta S.
    • Journal Title

      Free Radic Biol Med

      Volume: 108 Pages: 300-310

    • DOI

      10.1016/j.freeradbiomed.2017.03.010

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Hydrogen Gas Inhalation on Muscular Damage using Mouse Hind Limb Ischemia Reperfusion Injury Model.2017

    • Author(s)
      Watanabe M., Kamimura N., Iuchi K., Nishimaki K., Yokota T., Ogawa R., Ohta S.
    • Journal Title

      Plastic and Reconstructive Surgery.

      Volume: 140 Issue: 6 Pages: 1195-1206

    • DOI

      10.1097/prs.0000000000003878

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure2017

    • Author(s)
      Ono T, Kamimura N, Matsuhashi T, Nagai T, Nishiyama T, Endo J, Hishiki T, Nakanishi T, Shimizu N, Tanaka H, Ohta S, Suematsu M, Ieda M, Sano M, Fukuda K, Kaneda R
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 39752-39752

    • DOI

      10.1038/srep39752

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity2016

    • Author(s)
      1.Settineri R, Ji J, Luo C, Ellithorpe RR, Mattos GFd, Rosenblatt S, LaValle J, Jinenez A, Ohta S, Nicolson GL
    • Journal Title

      American J Food Nutr.

      Volume: 4 Pages: 161-168

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome – First-in-Human Pilot Study –2016

    • Author(s)
      Tamura T, Hayashida K, Sano M, Suzuki M, Shibusawa T, Yoshizawa J, Kobayashi Y, Suzuki T, Ohta S, Morisaki H, Fukuda K, Hori S.
    • Journal Title

      Circulation Journal

      Volume: 80 Issue: 8 Pages: 1870-1873

    • DOI

      10.1253/circj.CJ-16-0127

    • NAID

      130005166118

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Moleculeh hydrogen improves cognitive abilityin mild cognitive impairment and modest Alzheimer's disease.2019

    • Author(s)
      Shigeo Ohta
    • Organizer
      Alzheimers and Parkinsons Diseases Program
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Hydrogen Medicine: from basic science to clinical applications2018

    • Author(s)
      Shigeo Ohta
    • Organizer
      第5回国際循環器科学アカデミー(IACS-AS) Second Announcement_Smolenice
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 水素医学のこの一年の発展2017-20182018

    • Author(s)
      太田成男
    • Organizer
      第8回日本分子状水素医学生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] タウリン大量療法による MELAS 脳卒中様発作の再発抑制2018

    • Author(s)
      太田成男
    • Organizer
      第18回日本ミトコンドリア学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 水素水の飲用によってApoE4遺伝子保因者の経度認知障害が改善する。2017

    • Author(s)
      太田成男
    • Organizer
      第7回日本分子状水素医学生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミトコンドリアからみた認知症予防2017

    • Author(s)
      太田 成男
    • Organizer
      睡眠・認知症予防シンポジウム3
    • Place of Presentation
      中部大学(愛知)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 分子水素の可能性2017

    • Author(s)
      太田 成男
    • Organizer
      第33回スパズム・シンポジウム
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] The molecular mechanism by which H2 regulates gene expression.What is the primary target of H2?2016

    • Author(s)
      Shigeo Ohta
    • Organizer
      3rd Symposium of Chinese Hydrogen Biomedical Association
    • Place of Presentation
      Taian City (China)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子状水素による酸化ストレス軽減と遺伝子発現制御:基礎医学から臨床応用へ2016

    • Author(s)
      太田 成男
    • Organizer
      日本臨床検査自動化学会第48回大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 細胞死を抑制する分子状水素2016

    • Author(s)
      太田 成男
    • Organizer
      第25回日本Cell Death学会学術集会
    • Place of Presentation
      品川区立総合区民会館(東京)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 水素研究のup-to-date2016

    • Author(s)
      太田 成男
    • Organizer
      第16回日本抗加齢医学会総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 分子状水素による遺伝子発現制御2016

    • Author(s)
      太田 成男
    • Organizer
      日本分子状水素医学生物学会設立記念大会(第6回年会)
    • Place of Presentation
      ワークピア横浜(神奈川)
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Introduction of Japanese Society of Hydrogen and current situation of hydrogen in Japan2016

    • Author(s)
      Shigeo Ohta
    • Organizer
      2016 KOREA International Symposium on Hydrogen
    • Place of Presentation
      Seoul(KOREA)
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 水素医学の創始、展開、応用とメカニズム2016

    • Author(s)
      太田 成男
    • Organizer
      NPO法人国際医科学研究会第12回フォーラム
    • Place of Presentation
      フクラシア品川(東京)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] ここまでわかった 水素水最新Q&A: 続・水素水とサビない身体2017

    • Author(s)
      太田 成男
    • Total Pages
      187
    • Publisher
      小学館
    • Related Report
      2016 Research-status Report
  • [Book] 老化制御と疾患-エイジング研究の進歩-2016

    • Author(s)
      太田 成男
    • Total Pages
      5
    • Publisher
      日本臨床
    • Related Report
      2016 Research-status Report
  • [Remarks] 順天堂大学研究者情報データベース

    • URL

      https://www.juntendo.ac.jp/graduate/kenkyudb/search/researcher.php?MID=5478

    • Related Report
      2018 Annual Research Report
  • [Remarks] 日本医科大学先端医学研究所細胞生物学

    • URL

      https://www.nms.ac.jp/ig/saiboseibutsu/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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