The effect of carbon monoxide in the intestinal inflammation

• Project/Area Number: 22590706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TAKAGI Tomohisa 京都府立医科大学, 医学(系)研究科(研究院), 講師 (70405257)
• Co-Investigator(Kenkyū-buntansha): NAITO Yuji 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00305575) ; 半田 修 京都府立医科大学, 医学(系)研究科(研究院), 講師 (90381970)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 一酸化炭素 / 潰瘍性大腸炎 / クローン病 / 炎症性腸疾患 / 抗炎症作用 / 粘膜治癒 / Trinitrobenzesulfonic acid / TNF-alpha / CINC-1

Research Abstract

An abundance of recent data on the cytoprotective and anti-inflammatory effect of carbon monoxide (CO) supports that CO is a promising therapeutic gas for various diseases. In the present study, we investigated whether the enema with CO-saturated saline as a novel therapeutic strategy was effective against intestinal inflammation. CO-saturated solution was made by bubbled 50% CO gas into saline. In results, the intrarectal administration of CO-saturated solution ameliorated TNBS-induced colitis and accelerated the healing of the colonic ulceration. Moreover, CO-saturated medium enhanced the migration of intestinal epithelial cells. Thus, the rectal administration of CO-saturated solution protected from the intestinal inflammation and accelerated the colonic ulcer healing. B ased on these data, CO mayrepresent a novel therapeutic approach for the treatment of inflammatory bowel disease.

Research Products

• [Journal Article] BTB and CNC Homolog 1 (Bach1) Deficiency Ameliorates TNBS Colitis in Mice: Role of M2 Macrophages and Heme Oxygenase-1 (2013)
  • Author(s): Harusato, A. Naito, Y. Takagi, T. Uchiyama, K. Mizushima, K. Hirai, Y. Higashimura, Y. Katada, K. Handa, O. Ishikawa, T. Yagi, N. Kokura, S. Ichikawa, H. Muto, A. Igarashi, K. Yoshikawa, T.
  • Journal Title: Inflamm Bowel Dis Volume: 19 Issue: 4 Pages: 740-753
  • DOI: 10.1097/mib.0b013e3182802968
  • Peer Reviewed
• [Journal Article] Hemin ameliorates indomethacin-induced small intestinal injury in mice through the induction of heme oxygenase-1 (2013)
  • Author(s): Hiroyuki Yoriki
  • Journal Title: J Gastroenterol Hepatol. Volume: Apr;28(4) Issue: 4 Pages: 632-638
  • DOI: 10.1111/jgh.12074
  • Peer Reviewed
• [Journal Article] A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise (2012)
  • Author(s): Aoi, W. Naito, Y. Takagi, T. Tanimura, Y. Takanami, Y. Kawai, Y. Sakuma, K. Hang, L. P. Mizushima, K. Hirai, Y. Koyama, R. Wada, S. Higashi, A. Kokura, S. Ichikawa, H. Yoshikawa, T.
  • Journal Title: Gut Volume: E-pub Issue: 6 Pages: 882-9
  • DOI: 10.1136/gutjnl-2011-300776
  • Peer Reviewed
• [Journal Article] Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression (2012)
  • Author(s): Higashimura Y, Naito Y, Takagi T, Mizushima K, Hirai Y, Harusato A, Ohnogi H, Yamaji R, Inui H, Nakano Y, Yoshikawa T
  • Journal Title: J Gastroenterol
  • NAID: 10031195116
  • Peer Reviewed
• [Journal Article] Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats (2012)
  • Author(s): Takagi, T. Naito, Y. Uchiyama, K. Okuda, T. Suzuki, T. Tsuboi, H. Mizushima, K. Handa, O. Yagi, N. Ichikawa, H. Yoshikawa, T.
  • Journal Title: Med Gas Res Volume: 2 Issue: 1 Pages: 23-23
  • DOI: 10.1186/2045-9912-2-23
  • Peer Reviewed
• [Journal Article] Hemopexin is upregulated in rat intestinal mucosa injured by indomethacin (2012)
  • Author(s): Takagi T, Naito Y, Okada H, Takaoka M, Oya-Ito T, Yamada S, Hirai Y, Mizushima K, Yoshida N, Kamada K,Katada K, Uchiyama K, Ishikawa T, Handa O, Yagi N, Konishi H, Kokura S, Ichikawa H, Yoshikawa T
  • Journal Title: J Gastroenterol Hepatol Volume: J Gastroenterol Hepatol Issue: s3 Pages: 70-75
  • DOI: 10.1111/j.1440-1746.2012.07076.x
  • Peer Reviewed
• [Journal Article] Therapeutic potential of carbon monoxide (CO) for intestinal inflammation (2012)
  • Author(s): Naito Y, Uchiyama K, Takagi T, Yoshikawa T
  • Journal Title: Curr Med Chem Volume: 19(1) Pages: 70-6
  • URL: http://www.eurekaselect.com/75561/article
  • Peer Reviewed
• [Journal Article] Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression (2012)
  • Author(s): Yasuki Higasimura
  • Journal Title: J Gastroenterol. Volume: Nov 28
  • Peer Reviewed
• [Journal Article] Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution (2011)
  • Author(s): Takagi T, Naito Y, Uchiyama K, Okuda T, Mizushima K, Suzuki T, Handa O, Ishikawa T, Yagi N, Kokura S, Ichikawa H, Yoshikawa T
  • Journal Title: World J Gastroenterol Volume: 17(33) Issue: 33 Pages: 3802-9
  • DOI: 10.3748/wjg.v17.i33.3802
  • Peer Reviewed
• [Journal Article] Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice (2011)
  • Author(s): Takagi T, Naito Y, Uchiyama K, Suzuki T, Hirata I, Mizushima K, Tsuboi H, Hayashi N, Handa O, Ishikawa T, Yagi N, Kokura S, Ichikawa H, Yoshikawa T
  • Journal Title: Dig Dis Sci Volume: 56 Issue: 6 Pages: 1663-71
  • DOI: 10.1007/s10620-010-1484-y
  • Peer Reviewed
• [Journal Article] Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency (2011)
  • Author(s): Harusato A, Naito Y, Takagi T, Uchiyama K, Mizushima K, Hirai Y, Yamada S, Tuji T, Yoriki H, Horie R, Inoue K, Fukumoto K, Handa O, Ishikawa T, Kokura S, Minamiyama Y, Ichikawa H, Muto A, Igarashi K, Yoshikawa T
  • Journal Title: Free Radic Res Volume: 45(6) Issue: 6 Pages: 717-727
  • DOI: 10.3109/10715762.2011.574287
  • Peer Reviewed
• [Journal Article] Heme oxygenase-1: a novel therapeutic target for gastrointestinal diseases (2011)
  • Author(s): Naito Y, Takagi T, Uchiyama K, Yoshikawa T
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 48 Issue: 2 Pages: 126-133
  • DOI: 10.3164/jcbn.10-61
  • NAID: 130004466629
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice (2011)
  • Author(s): Hirata I, Naito Y, Takagi T, Mizushima K, Suzuki T, Omatsu T, Handa O, Ichikawa H, Ueda H, Yoshikawa T
  • Journal Title: Dig Dis Sci Volume: 56(5) Issue: 5 Pages: 1379-86
  • DOI: 10.1007/s10620-010-1461-5
  • Peer Reviewed
• [Journal Article] Heme oxygenase-CO系の制御は炎症性腸疾患治療につながる (2011)
  • Author(s): 高木智久、内藤裕二、吉川敏一
  • Journal Title: G.I.Research Volume: 19(1) Pages: 63-73
• [Journal Article] Inhalation of carbon monoxide ameliorates TNBS-induced colitis in mice through the inhibition of TNF-alpha expression (2010)
  • Author(s): Takagi T, Naito Y, Mizushima K, Akagiri S, Suzuki T, Hirata I, Omatsu T, Handa O, Kokura S, Ichikawa H, Yoshikawa T
  • Journal Title: Dig Dis Sci Volume: 55 Issue: 10 Pages: 2797-2804
  • DOI: 10.1007/s10620-009-1112-x
  • Peer Reviewed
• [Journal Article] The role of heme oxygenase and carbon monoxide in inflammatory bowel disease (2010)
  • Author(s): Takagi T, Naito Y, Uchiyama K, Yoshikawa T
  • Journal Title: Redox Rep Volume: 15(5) Issue: 5 Pages: 193-201
  • DOI: 10.1179/174329210x12650506623889
  • Peer Reviewed
• [Journal Article] Carbon monoxide enhance colonic epithelial restitution via FGF15 derived from colonic myofibroblasts (2010)
  • Author(s): Uchiyama K, Naito Y, Takagi T, Mizushima K, Hayashi N, Harusato A, Hirata I, Omatsu T, Handa O, Ishikawa T, Yagi N, Kokura S, Yoshikawa T
  • Journal Title: Biochem Biophys Res Commun Volume: 391 Issue: 1 Pages: 1122-6
  • DOI: 10.1016/j.bbrc.2009.12.035
  • Peer Reviewed
• [Journal Article] Carbon Monoxide Liberated from Carbon Monoxide-Releasing Molecule Exerts an Anti-inflammatory Effect on Dextran Sulfate Sodium-Induced Colitis in Mice. (2010)
  • Author(s): Takagi T., et al.
  • Journal Title: Dig Dis Sci. Volume: (掲載確定、2010.Nov.18にEpub ahead of print (on line) 印刷中)
  • Peer Reviewed
• [Journal Article] The role of heme oxygenase and carbon monoxide in inflammatory bowel disease. (2010)
  • Author(s): Takagi T., et al.
  • Journal Title: Redox Rep. Volume: 15 Pages: 193-201
  • Peer Reviewed
• [Presentation] シンポジウム 5「炎症制御とガスバイオロジーの接点」一酸化炭素(Carbon monoxide: CO)による腸管炎症制御 (2011)
  • Author(s): 高木智久、 内藤裕二、内山和彦、吉川敏一
  • Organizer: 32回日本炎症・再生医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-03
• [Presentation] 一酸化炭素(Carbon monoxide : CO)による腸管炎症制御 (2011)
  • Author(s): 高木智久、内藤裕二、内山和彦、吉川敏一
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都.国際会議場
  • Year and Date: 2011-06-03
• [Presentation] ベーシックサイエンス企画 シンポジウム 1「抗酸化環境応答と加齢」消化管炎症における抗酸化環境応答 (2011)
  • Author(s): 高木智久、内藤裕二、吉川敏一
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-05-27
• [Presentation] メディカルバイオガスの進歩と応用.一酸化炭素による腸管炎症制御を目指して (2011)
  • Author(s): 高木智久
  • Organizer: 第11回NO学会学術集会
  • Place of Presentation: 町田.昭和薬科大学
  • Year and Date: 2011-05-14
• [Presentation] シンポジウム 1「炎症性腸疾患の免疫病態 -Bench&Bedside Heme oxygenase-1発現制御性転写因子Bach1の抑制は腸管炎症を改善する. (2011)
  • Author(s): 高木智久、 内藤裕二、春里暁人、辻 俊史、寄木浩行、堀江隆介、内山和彦、堅田和弘、水島かつら、平井泰子、半田 修、八木信明、市川 寛、武藤哲彦、五十嵐和彦、吉川敏一
  • Organizer: 第48回日本消化器免疫学会総会
  • Place of Presentation: 金沢
• [Presentation] Carbon monoxide (CO)-saturated sodium enema ameliorates trinitrobenzene sulfonic acid-induced colitis in rats (2010)
  • Author(s): Takagi T, Naito Y, Uchiyama K, Okuda T, Hirata I, Omatsu T, Mizushima K, Hayashi N, Handa O, Ishikawa T, Yagi N, Kokura S, Yoshiakwa T
  • Organizer: The 6thInternational Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto
  • Year and Date: 2010-06-14
• [Presentation] The role of BACH1 in Dextran Sodium Sulfate (DSS)-Induced Colitis in Mice (2010)
  • Author(s): Takagi T, Naito Y, Harusato A, Yamada S, Fukumoto K, Inoue K, Horie R, Mizushima K, Omatsu T, Hirata I, Yoshida N, Uchiyama K, Uchiyama K, Ishikawa T, Handa O, Konishi H, Wakabayashi N, Yagi N, Kokura S, Ichikawa H, Muto A, Igarashi K, Yoshikawa T
  • Organizer: The 111th Annual Meeting of the AGA Institute. Digestive Disease Week
  • Place of Presentation: New Orleans, USA.
  • Year and Date: 2010-05-02
• [Book] Free radicals in inflammatory bowel disease (2011)
  • Author(s): Takagi T, Naito Y, Yoshikawa T
• [Book] CO and its application to Gastrointestinal disease (2011)
  • Author(s): Naito Y, Uchiyama K, Takagi T, Yoshikawa T
• [Book] Role of hydrogen sulfide in colitis (2011)
  • Author(s): Takagi T, Naito Y, Hirata I, Yoshikawa T
• [Book] Gas Biology Research in Clinical Practice (2011)
  • Author(s): Yoshikawa T, Naito Y
  • Total Pages: 148
  • Publisher: Karger, Basel
• [Patent(Industrial Property Rights)] 腸炎抑制及び飲食品 (2013)
  • Inventor(s): 矢嶋信浩、福家暢夫、内藤裕二、高木智久、岸 惇子、赤谷 薫
  • Industrial Property Rights Holder: 矢嶋信浩、福家暢夫、内藤裕二、高木智久、岸 惇子、赤谷 薫
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-040048
  • Filing Date: 2013-02-28