The effects of hydrogen gas breathing on the lung injury induced by hyperoxia

• Project/Area Number: 21591002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kitasato University
• Principal Investigator: KOBAYASHI Hirosuke 北里大学, 医療衛生学部, 教授 (70153632)
• Co-Investigator(Kenkyū-buntansha): HIROSE Minoru 北里大学, 医療衛生学部, 教授 (50286382) ; KOKUBO Kenichi 北里大学, 医療衛生学部, 准教授 (20287965) ; SHINBO Toshihiro 北里大学, 医療衛生学部, 助教 (10406910) ; KUBOTA Masaru 北里大学, 医学部, 准教授 (00234500) ; HATAISHI Ryuji 北里大学, 医学部, 講師 (20276124)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 非閉塞性肺疾患癌 / 肺線維症 / 呼吸器感染症 / その他・酸素障害 / 酸素障害 / 肺障害 / 酸素 / 活性酸素 / 水素 / 一酸化窒素 / 活性酵素

Research Abstract

Survival time of mice exposed to hyperoxia became longer when the mice breathed hydrogen gas, and the leukocytes accumulation in the lungs was reduced. Hydrogen gas protected cultured human alveolar epithelial cells against antimycin A-induced oxidative stress. The level of superoxide produced by mitochondria was significantly low, and the increase in superoxide produced by antimycin A was also lower in the presence of hydrogen gas. Hydrogen gas protected lungs against hyperoxic lung injury.

Research Products

• [Journal Article] Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+Th cells cytotoxic by activating both perforin-and FasLpathways (2012)
  • Author(s): Eshima E, Chiba S, Suzuki H, Kokubo K, Kobayashi H, Iizuka M, Iwabuchia K, Shinohara N
  • Journal Title: Immunology Letters Volume: 144 Pages: 7-15
  • Peer Reviewed
• [Journal Article] Rapid deconjugation of SN. 38 glucuronide and adsorption of released free SN. 38 by intestinal microorganisms in rat (2011)
  • Author(s): Takakura A, Kurita A, Asahara T, Yokoba M, Yamamoto M, Ryuge S, Igawa S, Yasuzawa Y, Sasaki J, Kobayashi H, Masuda N
  • Journal Title: Oncology letters Volume: 3 Pages: 520-524
  • Peer Reviewed
• [Journal Article] Prevalence of topoisomerase I genetic mutations and UGT1A1 polymorphisms associated with irinotecan in individuals of Asian descent (2011)
  • Author(s): Fukui T, Mitsufuji H, Kubota M, Inaoka H, Hirose M, Iwabuchi K, Masuda N, Kobayashi H
  • Journal Title: Oncology letters Volume: 2 Pages: 923-928
  • Peer Reviewed
• [Journal Article] X-ray radiation causes electromagnetic interference in implantable cardiac pacemakers (2010)
  • Author(s): Hirose M, Tachikawa K, Ozaki M, Umezawa N, Shinbo T, Kokubo K, Kobayashi H
  • Journal Title: Pacing Clin Electrophysiol Volume: 33 Pages: 1174-1181
  • Peer Reviewed
• [Journal Article] Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer (2010)
  • Author(s): Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Kokubo K, KobayashiH, Kim M S, Sidransky D, Watanabe M
  • Journal Title: Oncogene Volume: 29 Pages: 3263-327
  • Peer Reviewed
• [Journal Article] Removal of an endotoxin fragment(Lipid A) by an endotoxin-retentive filter (2010)
  • Author(s): Kokubo K, Futatsugi K, Tsukao H, Shinbo T, Hirose M, Kobayashi H
  • Journal Title: Desalination and Water Treatment Volume: 17 Pages: 25-30
  • Peer Reviewed
• [Journal Article] Macrophages that survive hyperoxia exposure have higher superoxide dismutase activities in their mitochondria (2010)
  • Author(s): Kokubo K, Soeda S, Shinbo T, Hirose M, Fuku N, Nishigaki Y, Tanaka M, Kobayashi H
  • Journal Title: Adv Exp Med Biol Volume: 662 Pages: 63-69
  • Peer Reviewed
• [Journal Article] Respiratory Rhythms in Healthy Subjects and Patients (2010)
  • Author(s): Shimane M, Tomita Y, Shinbo T, Kokubo K, Hirose M, Hataishi R, Kubota M, Masuda N, Kobayashi H
  • Journal Title: Advances in Experimental Medicine & Biology Volume: 662 Pages: 133-40
  • Peer Reviewed
• [Journal Article] Effect of gefitinib on warfarin antithrombotic activity (2009)
  • Author(s): Arai S, Mitsufuji H, Nishii Y, Onda S, Ryuge S, Wada M, Katono K, Iwasaki M, Takakura A, Otani S, Yamamoto M, Yanaihara T, Yokoba M, Kubota M, Katagiri M, Fukui T, Kobayashi H. Yanase N, Hataishi R, Masuda N
  • Journal Title: Int J Clin Oncol Volume: 14 Pages: 332-336
  • NAID: 10025864157
  • Peer Reviewed
• [Journal Article] Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone (2009)
  • Author(s): Ogata S, Ogihara Y, Nomoto K, Akiyama K, Nakahata Y, Sato K, Minoura K, Kokubo K, Kobayashi H, Ishii M
  • Journal Title: Pediatric Research Volume: 66 Pages: 577-584
  • Peer Reviewed
• [Journal Article] Low frequency oscillometry parameters in COPD patients are less variable during inspiration than during expiration (2009)
  • Author(s): Kubota M, Shirai G, Nakamori T, Kokubo K, Masuda N, Kobayashi H
  • Journal Title: Respir Physiol Neurobiol. Volume: 166 Pages: 73-79
  • Peer Reviewed
• [Presentation] 心筋虚血-再灌流障害に対する水素・一酸化窒素併用吸入の効果 (2012)
  • Author(s): 佐藤友理, 新保年弘, 畑石隆治, 小久保謙一, 廣瀬稔, 小林弘祐
  • Organizer: 第2回分子状水素医学シンポジウム
  • Place of Presentation: 北里大学白金キャンパス(東京)
  • Year and Date: 2012-02-11
• [Presentation] 誤嚥性肺炎マウスモデルにおける肺障害および遠隔臓器障害への水素吸入の効果 (2011)
  • Author(s): 畑石隆治, 西川優希, 新保年弘, 佐藤友里, 野田健太郎, 小久保謙一, 益田典幸, 小林弘祐
  • Organizer: 第5回iPUC-II (Integrated Pulmonary Circulation Research-II)
  • Place of Presentation: 東京ステーションコンファレンス(東京)
  • Year and Date: 2011-06-25
• [Presentation] Possible applications of hydrogen gas and nitric oxide for the therapy of critical illness. Invited lecture in the Symposium III : Applications of the Medical Gases NO, CO, H2S and H2 in Critical Illness (2011)
  • Author(s): Kobayashi H
  • Organizer: Shock Society 24th annual conference
  • Place of Presentation: Norfolk, USA
  • Year and Date: 2011-06-14
• [Presentation] Possible applications of hydrogen gas and nitric oxide for the therapy of critical illness (2011)
  • Author(s): Kobayashi H
  • Organizer: Shock Society 24^<th> annual conference
  • Place of Presentation: Norfolk, Virginia(招待講演)
  • Year and Date: 2011-06-14
• [Presentation] マウス心筋虚血-再灌流障害モデルに対する水素・-酸化窒素併用吸入の効果 (2011)
  • Author(s): 小林弘祐
  • Organizer: 分子状水素医学シンポジウム
  • Place of Presentation: 名古屋大学(名古屋)
  • Year and Date: 2011-02-19
• [Presentation] Increased surface coverage area of polyvinylpyrrolidone on polysulfone hemofilter membrane improves biocompatibility by suppressing cell adhesion during continuous hemofiltration (2011)
  • Author(s): Kurihara Y, Kokubo K, Tsukao H, Shinbo T, Hirose M, Kobayashi H
  • Organizer: 16th International Conference on Continuous Renal Replacement Therapies CRRT2001
  • Place of Presentation: San Diego, USA
• [Presentation] Simultaneous inhalation of nitric oxide and hydrogen reduces infarct size in the mouse model of myocardial ischemia- reperfusion injury. (2010)
  • Author(s): Shinbo T, Sato Y, Hataishi R, Kokubo K, Hirose M, Kobayashi H
  • Organizer: 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: 国際会館(Kyoto)
  • Year and Date: 2010-06-18
• [Presentation] Urea concentrating ability of artificial renal tubule based on countercurrent multiplier system using electrodialysis, dialysis and filtration (2010)
  • Author(s): Harashima T, Otani Y, Kokubo K, Tsukao H, Shinbo T, Hirose M, Sakai K, Kobayashi H
  • Organizer: World Conference on portable-wearable and miniaturized systems for dialysis and ultrafiltration and 3rd Annual Congress of the International Society for hemodialysis
  • Place of Presentation: Vicenza, Italy
• [Presentation] Dialysate-based perfusate of low viscosity is suitable for normothermic ex vivo lung perfusion (2010)
  • Author(s): Noda K, Kokubo K, Shinbo T, Hirose M, Kobayashi H
  • Organizer: ERS Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Presentation] Inhaled hydrogen during mechanical ventilation and hydrogen generated by enterobacterial flora reduce infarct size in the mouse model of myocardial ischemia-reperfusion injury (2010)
  • Author(s): Sato Y, Shinbo T, Hataishi R, Kokubo K, Hirose M, Kobayashi H
  • Organizer: European Respiratory Society Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Presentation] Hydrogen protects alveolar epithelial cells(A549) against injury induced by reactive oxygen species in vitro (2010)
  • Author(s): Kokubo K, Yamashita K, Shinbo T, Hirose M, Kobayashi H
  • Organizer: European Respiratory Society Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Presentation] Temporal changes in gene expressions and cytokine productions caused by stretching of normal human pulmonary artery endothelial cells (2010)
  • Author(s): Kobayashi K, Tanaka M, Inaoka H, Nebuya S, Fukuoka Y, Kokubo K, Kobayashi H, Noshiro M
  • Organizer: European Respiratory Society Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Presentation] Differentiation of side population cells isolated from human amniotic mesenchymal cell into vascular endothelial cells under hypoxic condition (2010)
  • Author(s): Maruyama N, Nishikubo Y, Kokubo K, Shinbo T, Hirose M, Kobayashi M, Sakuragawa N, Kobayashi H
  • Organizer: Tissue Engineering & Regenerative Medicine International Society 2010 Asia Pacific meeting, TERMIS-AP 2010 Annual Conference
  • Place of Presentation: Sydney, Australia
• [Presentation] Differentiation into neural cells from human amniotic mesenchymal cell in serum free medium (2010)
  • Author(s): Nishikubo Y, Maruyama N, Kokubo K, Shinbo T, Hirose M, Kobayashi M, Sakuragawa N, Kobayashi H
  • Organizer: Tissue Engineering & Regenerative Medicine International Society 2010 Asia Pacific meeting, TERMIS-AP 2010 Annual Conference
  • Place of Presentation: Sydney, Australia
• [Presentation] Comparison of the effects of the dilution mode on inflammation and lymphocyte function between predilution and postdilution hemodiafiltration (2010)
  • Author(s): Sakurai K, Saito T, Kokubo K, Asahi D, Yamauchi F, Hosoya H, Maruyama N, Kobayashi H
  • Organizer: 47th ERA-EDTA Congress
  • Place of Presentation: Munich
• [Presentation] Suppression of platelet Activation on the surface of dialysis membrane releasing nitric oxide from the dialysate (2010)
  • Author(s): Urabe S, Kokubo K, Tsukao H, Shinbo T, Hirose M, Kobayashi H
  • Organizer: 47th ERA-EDTA Congress
  • Place of Presentation: Munich
• [Presentation] Activation of platelets in contact with oxidized vitamin E-coated surface (2010)
  • Author(s): Tsukao H, Kokubo K, Nagasato M, Shinbo T, Hirose M, Kobayashi H
  • Organizer: 47th ERA-EDTA Congress
  • Place of Presentation: Munich
• [Presentation] Simultaneous inhalation of nitric oxide and hydrogen reduces infarct size in the mouse model of myocardial ischemia-reperfusion injury (2010)
  • Author(s): Shinbo T, Sato Y, Hataishi R, Kokubo K, Hirose M, Kobayashi H
  • Organizer: 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto
• [Presentation] Dialysis membrane releasing nitric oxide from dialysate side increases cyclic guanosine monophosphate in platelets and suppresses the activation of platelets on the surface (2010)
  • Author(s): Kokubo K, Urabe S, Tsukao H, Shinbo T, Hirose M, Kobayashi H
  • Organizer: 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto
• [Presentation] Inhaled hydrogen during mechanical ventilation and hydrogen generated by enterobacterial flora reduce infarct size in the mouse model of myo-cardial ischemia-reperfusion injury. (2010)
  • Author(s): Sato Y, Shinbo T, Hataishi R, Kokubo K, Hirose M, Kobayashi H.
  • Organizer: European Respiratory Society Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Presentation] Hydrogen protects alveolar epithelial cells(A549)against injury induced by reactive oxygen species in vitro. (2010)
  • Author(s): Kokubo K, Yamashita K, Shinbo T, Hirose M, Kobayashi H.
  • Organizer: European Respiratory Society Annual Congress 2010
  • Place of Presentation: Barcelona, Spain
• [Patent(Industrial Property Rights)] 虚血再潅流障害軽減用治療剤および治療装置 (2010)
  • Inventor(s): 小林弘祐,小久保謙一,新保年弘
  • Industrial Property Rights Holder: 学校法人北里研究所
  • Industrial Property Number: 2010-053405
  • Filing Date: 2010-03-10
• [Patent(Industrial Property Rights)] 虚血再潅流障害軽減用治療剤および治療装置 (2010)
  • Inventor(s): 小林弘祐、小久保謙一、新保年弘
  • Industrial Property Rights Holder: 学校法人北里研究所
  • Industrial Property Number: 2010-053405
  • Filing Date: 2010-03-10