Treatment strategy for liver fibrosis by hydrogen water

• Project/Area Number: 23659647
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: TAURA Kojiro 京都大学, 医学研究科, 助教 (80378629)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝線維化 / 活性酸素 / 星細胞 / 肝細胞 / 肝卵形細胞 / 水素水

Research Abstract

To investigate the effects of hydrogen water on liver fibrogenesis, C57BL/6 mice were fed with hydrogen water or control water, and subjected to carbon tetrachloride, thioacetamide and bile duct ligation treatments to induce liver fibrosis. Oral intake of hydrogen water significantly suppressed liver fibrogenesis in the carbon tetrachloride and thioacetamide models, but these effects were not seen in the bile duct ligation model.To investigate the mechanisms underlying these effects, hepatocytes and hepatic stellate cells were isolated from mice and cultured with or without hydrogen to test the effects of hydrogen on reactive oxygen species-induced hepatocyte injuries or hepatic stellate cell activation. Treatment of isolated hepatocyte with 1 μg/mL antimycin A generated hydroxyl radicals. Culturing in the hydrogen-rich medium selectively suppressed the generation of hydroxyl radicals in hepatocytes and significantly suppressed hepatocyte death induced by antimycin A; however, it did not suppress hepatic stellate cell activation. We conclude that hydrogen water protects hepatocytes from injury by scavenging hydroxyl radicals and thereby suppresses liver fibrogenesis in mice.

Research Products

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• [Journal Article] Effect of olprinone on liver microstructure in rat partial liver transplantation. (2012)
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• [Journal Article] Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells (2011)
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• [Journal Article] A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer (2011)
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• [Journal Article] Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography in patients with extrahepatic bile duct cancer (2011)
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• [Journal Article] 他科との連携手術-知っておくべき最新の知識 (2011)
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• [Journal Article] Prognostic Value of Intraoperative Peritoneal Cytology in Biliary Tract Cancer (2011)
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• [Journal Article] 肝区域と画像診断update (2011)
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• [Journal Article] Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. (2011)
  • Author(s): Kitamura K, Taura K et al.
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• [Presentation] 3D CT cholangiographyを活用した肝門部胆管癌に対する術式選択と手術プラニング (2012)
  • Author(s): 田浦 康二朗
  • Organizer: 日本外科学会総会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] Plissimo Eraを用いた 肝切除術のVirtual Reality (2012)
  • Author(s): 田浦 康二朗
  • Organizer: 日本消化器外科学会
  • Place of Presentation: 富山国際会議場（富山市）
• [Presentation] Usefulness of Liver Stiffness Measurement for the Prediction of Posthepatectomy Liver Failure (2012)
  • Author(s): Taura Kojiro
  • Organizer: The 63rd Annual Meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: Hynes Convention Center (Boston, USA)
• [Presentation] 肝胆膵外科における Virtual 3D画像と 臓器立体モデルへの取り組み (2012)
  • Author(s): 田浦 康二朗
  • Organizer: 日本内視鏡外科学会総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] Three-Dimensional Image of Hepatic Hilum by CT Cholangiography with Carbon Dioxide for Preoperative Assessment of Biliary Malignancies (2012)
  • Author(s): 田浦 康二朗
  • Organizer: Internationa Forum of Liver Surgery
  • Place of Presentation: セイコーグランドホテル（秋田県）