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

2013 Fiscal Year Final Research Report

• 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
• 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
  • 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 (2013)
  • Author(s): Ogaki S, Taguchi K, Watanabe H, Otagiri M, Maruyama T
  • Journal Title: Drug Metabolism and Disposition Volume: 41(1) Pages: 141-8
  • DOI: 10.1124/dmd.112.048744
  • 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, Yaegashi N
  • Journal Title: Life Sciences Volume: 91(11-12) Pages: 420-8
  • DOI: 10.1016/j.lfs.2012.08.021
  • 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
  • Year and Date: 20131206-07
• [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
  • Year and Date: 20131121-22
• [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