Carbon monoxide-bound hemoglobin-vesicles as a potential therapeutic agent for the treatment of bleomycin-induced pulmonary fibrosis

• Project/Area Number: 24790159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Sojo University (2013); Kumamoto University (2012)
• Principal Investigator: TAGUCHI Kazuaki 崇城大学, 薬学部, 助教 (90621912)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヘモグロビン / リポソーム / 一酸化炭素 / 特発性肺線維症

Research Abstract

Carbon monoxide (CO) has potent anti-inflammatory and anti-oxidant effects. We preparate a CO-bound hemoglobin-vesicles (CO-HbV), and evaluated the therapeutic effect of CO-HbV on idiopathic pulmonary fibrosis (IPF) that is thought to involve inflammation and the production of reactive oxygen species (ROS). CO-HbV suppressed the progression of pulmonary fibril formation and improved respiratory function compared to saline and HbV in a bleomycin-induced pulmonary fibrosis mice model. The suppressive effect of CO-HbV on pulmonary fibrosis can be attributed to a decrease in ROS generation by inflammatory cells, cytokines and transforming growth factor-beta in the lung. This is the first demonstration of the inhibitory effect of CO-HbV on the progression of pulmonary fibrosis via the anti-oxidative and anti-inflammatory effects of CO in the bleomycin-induced pulmonary fibrosis mice model.

Research Products

• [Journal Article] Carbon monoxide-bound hemoglobin-vesicles for the treatment of bleomycin-induced pulmonary fibrosis. (2014)
  • Author(s): Nagao S, Taguchi K, Sakai H, Tanaka R, Horinouchi H, Watanabe H, Kobayashi K, Otagiri M, Maruyama T.
  • Journal Title: Biomaterials. Volume: 35 Issue: 24 Pages: 6553-6562
  • DOI: 10.1016/j.biomaterials.2014.04.049
  • Peer Reviewed
• [Journal Article] Carbon Monoxide Bound Red Blood Cells Protect Red Blood Cell Transfusion-induced Hepatic Cytochrome P450 Impairment in Hemorrhagic-shock Rats. Drug Metab Dispos. (2013)
  • Author(s): Ogaki S, Taguchi K, Watanabe H, Otagiri M, and Maruyama T.
  • Journal Title: Drug Metab Dispos. Volume: 41 Issue: 1 Pages: 141-8
  • DOI: 10.1124/dmd.112.048744
  • Peer Reviewed
• [Journal Article] Pharmacokinetic study of adenosine diphosphate-encapsulated liposomes coated with fibrinogen γ-chain dodecapeptide as a synthetic platelet substitute in an anticancer drug-induced thrombocytopenia rat model. (2013)
  • Author(s): Taguchi K, Ujihira H, Watanabe H, Fujiyama A, Doi M, Takeoka S, Ikeda Y, Handa M, Otagiri M, Maruyama T.
  • Journal Title: J Pharm Sci. Volume: 102 Issue: 10 Pages: 3852-9
  • DOI: 10.1002/jps.23692
  • Peer Reviewed
• [Journal Article] Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen γ-chain dodecapeptide as a synthetic platelet substitute. (2013)
  • Author(s): Taguchi K, Ujihira H, Ogaki S, Watanabe H, Fujiyama A, Doi M, Okamura Y, Takeoka S, Ikeda Y, Handa M, Otagiri M, Maruyama T.
  • Journal Title: Drug Metab Dispos. Volume: 41 Issue: 8 Pages: 1584-91
  • DOI: 10.1124/dmd.112.050005
  • Peer Reviewed
• [Journal Article] A reduced linezolid dosage maintains favorable efficacy with minimal hematologic toxicity in a methicillin-resistant Staphylococcus aureus-infected patient with renal insufficiency. (2013)
  • Author(s): Taguchi K
  • Journal Title: Scand J Infect Dis. Volume: 45(1) Issue: 1 Pages: 77-80
  • DOI: 10.3109/00365548.2012.708783
  • Peer Reviewed
• [Journal Article] Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model. (2012)
  • Author(s): Kaga M, Li H, Ohta H, Taguchi K, Ogaki S, Izumi H, Inagaki M, Tsuchiya S, Okamura K, Otagiri M, Sakai H, and Yaegashi N.
  • Journal Title: Life Sci. Volume: 91 Issue: 11-12 Pages: 420-8
  • DOI: 10.1016/j.lfs.2012.08.021
  • Peer Reviewed
• [Journal Article] Effect of acetaminophen on progression of renal damage in adenine induced renal failure model rat. (2012)
  • Author(s): Kadowaki D, Sumikawa S, Arimizu K, Taguchi K, Kitamura K, Ishitsuka Y, Narita Y, Irie T, Maruyama T, Otagiri M, Hirata S
  • Journal Title: Life Sci. Volume: 91 Issue: 25-26 Pages: 1304-1308
  • DOI: 10.1016/j.lfs.2012.09.018
  • Peer Reviewed
• [Journal Article] Carvedilol enhances mesenchymal stem cell therapy for myocardial infarction via inhibition of caspase-3 expression. (2012)
  • Author(s): Hassan F
  • Journal Title: J Pharmacol Exp Ther. Volume: 343(1) Issue: 1 Pages: 62-71
  • DOI: 10.1124/jpet.112.196915
  • Peer Reviewed
• [Journal Article] Pharmaceutical aspects of the recombinant human serum albumin dimer: structural characteristics, biological properties, and medical applications. (2012)
  • Author(s): Taguchi K, Chuang VT, Maruyama T, Otagiri M.
  • Journal Title: J Pharm Sci. Volume: 101 Issue: 9 Pages: 3033-46
  • DOI: 10.1002/jps.23181
  • Peer Reviewed
• [Presentation] 一酸化炭素付加型ヘモグロビン小胞体の特発性肺線維症治療薬としての創製 (2013)
  • Author(s): 田口和明, 他
  • Organizer: 第20回日本血液代替物学会年次大会
  • Place of Presentation: 奈良
• [Presentation] Carbon monoxide bound red blood cells protect the expression of hepatic cytochrome P450 after resuscitation from hemorrhagic shock via inactivation of Kupffer cells (2013)
  • Author(s): Ogaki S, Taguchi K, 他
  • Organizer: Asian Federation for Pharmaceutical Sciences 2013
  • Place of Presentation: Jeju, Korea
• [Presentation] Preclinical studies of hemoglobin-vesicles as an artificial oxygen carrier in non-human primate (2013)
  • Author(s): Kazuaki Taguchi, Hiromi Sakai, Hirohisa Horinouchi, Koichi Kobayashi, Toru Maruyama, Masaki Otagiri
  • Organizer: The XIVth International Symposium on Blood Substitutes and Oxygen Therapeutics
  • Place of Presentation: Chengdu, China
• [Presentation] 一酸化炭素付加型ヘモグロビン小胞体の特発性肺線維症治療薬としての創製 (2013)
  • Author(s): 田口和明、永尾紗理、丸山徹、小田切優樹
  • Organizer: 第20回日本血液代替物学会年次大会
  • Place of Presentation: 奈良県新公会堂
  • Invited
• [Presentation] 細胞型人工酸素運搬体ヘモグロビン小胞体のカニクイザルへの大量投与の結果からみた実効性 (2012)
  • Author(s): 田口和明、酒井宏水、堀之内宏久、小林紘一、丸山徹、小田切優樹
  • Organizer: 第19日本血液代替物学会年次大会
  • Place of Presentation: 旭川大雪クリスタルホール
• [Presentation] 骨髄指向性を有する新規エリスロポエチン製剤の開発 (2012)
  • Author(s): 宮崎裕理、田口和明、宗慶太郎、小田切優樹、丸山徹
  • Organizer: 日本薬剤学会27年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 血小板代替物H12(ADP)リポソームの体内動態に及ぼす血小板減少症の影響 (2012)
  • Author(s): 10. 丸山徹、田口和明、氏平隼人、渡邊博志、新井愛美、池田康夫、武岡真司、半田誠、小田切優樹
  • Organizer: 第19日本血液代替物学会年次大会
  • Place of Presentation: 旭川大雪クリスタルホール
• [Presentation] Preclinical studies of hemoglobin-vesicles as an artificial oxygen carrier in non-human primate
  • Author(s): Taguchi K, 他
  • Organizer: 14th International Symposium on Blood Substitutes and Oxygen Therapeutics