Molecular hydrogen medicine: Possible mechanisms of hydrogen antioxidant activity

• Project/Area Number: 24500882
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: OHSAWA Ikuroh 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (30343586)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 水素分子 / 酸化ストレス / ミトコンドリア / 培養細胞 / 抗がん剤副作用 / マウスモデル / 細胞 / 健康長寿

Outline of Final Research Achievements

Molecular hydrogen (H2) selectively reduces toxic reactive oxygen species including hydroxyl radical and ameliorates oxidative stress-induced injuries in vivo. However, precise mechanisms underlying the remarkable effect with a small amount of H2 remain unclear. In the current study, we investigated the effect of H2 on mitochondria in cultured neuroblastoma SH-SY5Y and found that H2 enhanced mitochondrial membrane potential and cellular ATP accompanying a decrease in reduced glutathione and an increase in superoxide. Pretreatment of cells with H2 suppressed the H2O2-induced cell death, whereas posttreatment did not. An increase in antioxidative enzymes of the pretreated cells indicated the possibility that a mild stress with H2 induce an increased resistance to exacerbated oxidative stress. We propose here that H2 functions both as a radical scavenger and “a mitohormetic effector” against oxidative stress.

Research Products

• [Journal Article] Stimulation of human damaged sperm motility with hydrogen molecule (2015)
  • Author(s): Nakata K, Yamashita N, Noda Y, Ohsawa I
  • Journal Title: Med Gas Res Volume: 5 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s13618-014-0023-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Multiple Effects of Molecular Hydrogen and its Distinct Mechanism (2014)
  • Author(s): Noda M, Fujita K, Ohsawa I, Ito M, Ohno K
  • Journal Title: J Neurol Disord Volume: 2 Issue: 06 Pages: 189-189
  • DOI: 10.4172/2329-6895.1000189
  • Peer Reviewed / Open Access
• [Journal Article] Preventive effects of Chlorella on skeletal muscle atrophy in muscle-specific mitochondrial aldehyde dehydrogenase 2 activity-deficient mice. (2014)
  • Author(s): Nakashima Y, Ohsawa I, Nishimaki K, Kumamoto S, Maruyama I, Suzuki Y, Ohta S
  • Journal Title: BMC Complement Altern Med Volume: 14 Issue: 1 Pages: 390-390
  • DOI: 10.1186/1472-6882-14-390
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of inosine produces antidepressant-like effects in mice (2014)
  • Author(s): Muto J, et al.
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 4199-4199
  • DOI: 10.1038/srep04199
  • Peer Reviewed
• [Journal Article] Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes. (2013)
  • Author(s): Tanisawa K., Mikami E., Fuku N., Honda Y., Honda S., Ohsawa I., Ito M., Endo S., Ihara K., Ohno K., Kishimoto Y., Ishigami A., Maruyama N., Sawabe M., Iseki H., Okazaki Y., Hasegawa-Ishii S., Takei S., Shimada A., Hosokawa M., Mori M., Higuchi K., Takeda T., Higuchi M., Tanaka M.
  • Journal Title: BMC Genomics. Volume: 14(1): Issue: 1 Pages: 248-248
  • DOI: 10.1186/1471-2164-14-248
  • Peer Reviewed / Open Access
• [Journal Article] Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells (2013)
  • Author(s): Iio A, Ito M, Itoh T, Terazawa R, Fujita Y, Nozawa Y, Ohsawa I, Ohno K, Ito M
  • Journal Title: Med Gas Res Volume: 3 Issue: 1 Pages: 6-6
  • DOI: 10.1186/2045-9912-3-6
  • Peer Reviewed
• [Journal Article] Histamine H1-Receptor Antagonistic Drug Olopatadine Suppresses TSLP in Atopic Dermatitis Model Mice (2013)
  • Author(s): Higashi M, et al
  • Journal Title: Allergology International Volume: 62 Issue: 1 Pages: 137-138
  • DOI: 10.2332/allergolint.12-LE-0466
  • NAID: 130004477165
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Molecular cloning and characterisation of a novel type of human papillomavirus 160 isolated from a flat wart of an immunocompetent patient (2013)
  • Author(s): Mitsuishi T, et al
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e79592-e79592
  • DOI: 10.1371/journal.pone.0079592
  • Peer Reviewed
• [Journal Article] 水素分子の疾患予防・治療効果 (2013)
  • Author(s): 大澤郁朗
  • Journal Title: 日本透析医会雑誌 Volume: 28 Pages: 261-267
  • Peer Reviewed
• [Journal Article] Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis (2012)
  • Author(s): Hoshi H, Hao W, Fujita Y, Funayama A, Miyauchi Y, Hashimoto K, Miyamoto K, (他21名)
  • Journal Title: J. Bone Miner Res Volume: 27(9) Issue: 9 Pages: 2015-2023
  • DOI: 10.1002/jbmr.1634
  • Peer Reviewed
• [Journal Article] 神経系における水素分子の抗酸化，抗炎症作用：研究の現状 (2012)
  • Author(s): 大澤郁朗
  • Journal Title: Clinical Neuroscience Volume: 30 Pages: 1320-1321
• [Journal Article] 水素分子の生理作用と水素水による疾患防御 (2012)
  • Author(s): 大澤郁朗
  • Journal Title: 日本老年医学会雑誌 Volume: 35 Pages: 680-688
  • Peer Reviewed
• [Presentation] Hydrogen water inhibits gefitinib-induced lung injury by anti-inflammatory effects (2015)
  • Author(s): Masumi Iketani, Kozue Tonaki, Tetsuya Suzuki, Jumi Ohshiro, Yasuhiro Terasaki, Mayumi Takahashi, Hideo Kawaguchi, Seisuke Hattori, Ikuroh Ohsawa
  • Organizer: 第５回分子状水素医学シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Physiological isotope effects of deuterium (2015)
  • Author(s): Maki Shibata, Kensi Koide, Mayumi Takahashi, Masumi Iketani, Hideo Kawaguchi, Ikuroh Ohsawa
  • Organizer: 第５回分子状水素医学シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] 水素分子による生体機能制御 (2015)
  • Author(s): 大澤郁朗
  • Organizer: 第２７回代用臓器再生医学研究会
  • Place of Presentation: 札幌
  • Year and Date: 2015-02-28
  • Invited
• [Presentation] 水素分子による障害精子の運動能改善 (2015)
  • Author(s): 大澤郁朗、野田義博、中田久美子、池谷真澄
  • Organizer: 第４回TOBIRA研究交流フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2015-02-02
• [Presentation] 水素分子のミトホルミシス効果と精子機能改善 (2014)
  • Author(s): 大澤郁朗、中田久美子、野田義博、村上弥生
  • Organizer: 第１４回日本ミトコンドリア学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-03 – 2014-12-05
• [Presentation] 分子状水素は活性酸素によるマウス精子運動能低下を改善する (2014)
  • Author(s): 野田義博、中田久美子、倉本和直、遠藤玉夫、山下直樹、大澤郁朗
  • Organizer: 第３７回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-24 – 2014-11-27
• [Presentation] 水素含有胚融解液はヒト凍結胚盤胞の生存能を向上させるか？ －水素分子をヒト胚に用いた初の試み－ (2014)
  • Author(s): 中田久美子、中山順樹、池上加代子、中西彩、阿部睦、渡邊ひとみ、山下直樹、大澤郁朗
  • Organizer: 第３２回日本受精着床学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-31 – 2014-08-01
• [Presentation] 水素分子処置によるヒト不動精子の運動性回復 (2014)
  • Author(s): 中田久美子，山下直樹，大澤郁朗
  • Organizer: 第５５回日本卵子学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] 分子状水素は活性酸素によるマウス精子前進性運動機能低下を抑制する (2014)
  • Author(s): 野田義博、中田久美子、倉本和直、遠藤玉夫、山下直樹、大澤郁朗
  • Organizer: 第５５回日本卵子学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] 活性酸素障害の新たな防御法 (2014)
  • Author(s): 大澤郁朗
  • Organizer: 第５４回日本呼吸器学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25 – 2014-04-27
  • Invited
• [Presentation] 高濃度水素水によるゲフィチニブの急性肺傷害抑制 (2014)
  • Author(s): 寺崎泰弘、大澤郁朗、鈴木徹也、渡名喜梢、漆山博和、寺崎美佳、功刀しのぶ、福田悠、清水章
  • Organizer: 第１０３回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 分子状水素による神経疾患の予防と治療 (2014)
  • Author(s): 大澤郁朗
  • Organizer: 第１０回認知症サプリメント研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-06
  • Invited
• [Presentation] 高濃度重水素含有水による炎症抑制効果の検討 (2014)
  • Author(s): 小出賢志、村上弥生、高橋真由美、川口英夫、大澤郁朗
  • Organizer: 第４回分子状水素医学シンポジウム
  • Place of Presentation: 東京
• [Presentation] 高濃度水素水はゲフィチニブの薬効を阻害することなく急性肺障害を抑制する (2014)
  • Author(s): 渡名喜梢、鈴木徹也、寺崎泰弘、村上弥生、高橋真由美、川口英夫、大澤郁朗
  • Organizer: 第４回分子状水素医学シンポジウム
  • Place of Presentation: 東京
• [Presentation] 高濃度水素水によるゲフィチニブの急性肺傷害抑制 (2013)
  • Author(s): 鈴木徹也、寺崎泰弘、渡名喜梢、大澤郁朗
  • Organizer: 日本基礎老化学会第３６回大会
  • Place of Presentation: 大阪
• [Presentation] Overview on new medical gases: molecular hydrogen medicine for neuroprotection and slow aging (2013)
  • Author(s): Ohsawa I
  • Organizer: Neuro2013
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] 水素分子処置によるヒト不動精子の運動性回復 (2013)
  • Author(s): 中田久美子，山下直樹，大澤郁朗
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 加齢に伴うマウス脳ミトコンドリア機能の低下は水溶性コエンザイムQ10飲水投与により回復する (2013)
  • Author(s): 高橋真由美、大澤郁朗、高橋和秀
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Molecular hydrogen as a radioprotector: Possible mechanisms of hydrogen antioxidant activity (2013)
  • Author(s): 大澤郁朗
  • Organizer: 第９０回日本生理学会大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Molecular Hydrogen Medicine: Possible Mechanisms of Hydrogen Antioxidant Activity (2012)
  • Author(s): Ohsawa I, Murakami Y, Aoki S, Tanaka M
  • Organizer: Annual Conference of the Korean Society for Gerontology, the 12th Korea-Japan Joint symposia
  • Place of Presentation: Osong, Republic of Korea
  • Invited
• [Presentation] 分子状水素による酸化ストレス抑制の分子機構 (2012)
  • Author(s): 大澤郁朗、村上弥生
  • Organizer: 日本基礎老化学会第３５回大会
  • Place of Presentation: 船橋
• [Presentation] 水素医学の現状と展望 (2012)
  • Author(s): 大澤郁朗
  • Organizer: 第１２回抗加齢医学の実際
  • Place of Presentation: 東京
  • Invited
• [Presentation] 水素分子による酸化ストレス防御の分子機構 (2012)
  • Author(s): 大澤郁朗、村上弥生
  • Organizer: 第１２回日本ミトコンドリア学会年会
  • Place of Presentation: 筑波
• [Book] 医療ガス情報ファイル (2013)
  • Author(s): 大澤郁朗
  • Total Pages: 36
  • Publisher: 住友精化株式会社
• [Remarks] 生体環境応答研究
  • URL: http://www.tmghig.jp/J_TMIG/kenkyu/team/seitaikankyooutou.html
• [Remarks] 生体環境応答研究
  • URL: http://www.tmghig.jp/J_TMIG/kenkyu/team/seitaikankyooutou.html
• [Remarks] Biological Process of Aging
  • URL: http://www.tmig.or.jp/research/DA24.html
• [Remarks] 環境老化研究
  • URL: http://www.tmghig.jp/J_TMIG/j_research/DA24.html