Innovative Approaches for Oxygen Metabolism Disorder with Artificial Oxygen Carriers and Related Compounds

2015 Fiscal Year Final Research Report

• Project/Area Number: 24249086
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Tokai University
• Principal Investigator: KAWAGUCHI Akira 東海大学, 医学部, 教授 (30195052)
• Co-Investigator(Kenkyū-buntansha): INOKUCHI Sadaki 東海大学, 医学部, 教授 (60160008) ; HAIDA Munetaka 東海大学医療技術短期大学, 看護学部, 教授 (20208408) ; SHIRAI Mikiyasu 独立行政法人国立循環器病研究センター, 心機能生理部, 部長 (70162758) ; NEYA Saburo 千葉大学, 薬学研究科(研究院), 教授 (10156169) ; YAMANO Mariko 大阪府立大学, 総合リハビリテーション学部, 准教授 (80192409) ; IMAI Kiyohiro 法政大学, 生命科学部, 教授 (50028528) ; KANO Koji 同志社大学, 工学部, 教授 (60038031) ; MURAYAMA Chieko 東海大学, 医学部, 講師 (50307295) ; TAMAKI Tetsuro 東海大学, 医学部, 准教授 (10217177) ; ENDO Hitoshi 東海大学, 医学部, 講師 (10550551) ; TSUNESHIGE Antonio 法政大学, 生命科学部, 教授 (30409346) ; OKU Naoto 静岡県立大学, 薬学部, 教授 (10167322)
• Co-Investigator(Renkei-kenkyūsha): IMAI Kiyohiro 法政大学, 生命科学部, 教授 (50028528)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 人工酸素運搬体 / 虚血 / 再灌流障害 / ヘモグロビン / 酸素代謝障害 / 一酸化炭素中毒 / シアン中毒 / 水素

Outline of Final Research Achievements

Blood circulation consists of heart(pump), vasculature(circuit)and blood(fluid). While derangement of any of them results in circulatory failure, approaches through the third component have been scarce except for transfusion. Whereas artificial oxygen carriers (AOC) remain short of red cells in health, their physical characteristics may work better in disease. In the current study, we tested various AOC and related compounds in animal models to show, 1)protection of ischemia and/or reperfusion injury in bronchus, stomach, brain, inner-ear, skin and skeletal muscle, 2)absence of competitive inhibition on antigen recognition by reticuloendothelial system after a large-dose administration, 3)enhanced radiotherapy and reduction on metastasis after chemotherapy. The results prompted us to change the hypothetical mechanism from aerobic energy synthesis to anti-inflammatory action through suppressed HIF-1a-mediated signal transduction, which better explains the current observations.

Free Research Field

循環不全