Protective effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659553
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Hirosaki University
• Principal Investigator: KASHIWAKURA Ikuo 弘前大学, 保健学研究科, 教授 (00177370)
• Co-Investigator(Kenkyū-buntansha): MONZEN Satoru 弘前大学, 保健学研究科, 助教 (20514136) ; YOSHINO Hironori 弘前大学, 保健学研究科, 助教 (10583734)
• Co-Investigator(Renkei-kenkyūsha): ITO Koichi 弘前大学, 保健学研究科, 教授 (90398579)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 医薬品 / 全身照射 / 急性放射線症候群 / romiprostim

Research Abstract

Different combinations of four drugs - recombinant human erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate (ND)- was administered to mice within 2 h after exposure to a lethal 7 Gy dose of gamma-irradiation.Approximately 10% of the untreated irradiated control mice survived for 27 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for three days immediately after irradiation led to a complete survival of the irradiated mice until day 30.However,the treatment with G-CSF and EPO with ND led to only 75% survival at day 30.The hematological analyses showed that the numbers of almost of hematopoietic cells in the surviving mice treated with effective medications recovered to the levels of non-irradiated mice.The present findings show that the combination of G-CSF, EPO and RP may be a useful countermeasure for victims exposed to accidental lethal irradiation.

Research Products

• [Journal Article] Long-lasting radioprotective effects of a combination of pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation (2014)
  • Author(s): M. Yamaguchi, T. Hirouchi, M. Nakano, S. Monzen, H. Yoshino, M. Chiba, J. Ishikawa, A. Nishiyama, S. Murakami, K. Ito and I. Kashiwakura
  • Journal Title: Radiat. Emerg. Med. Volume: 3(1) Pages: 50-55
  • Peer Reviewed
• [Journal Article] Mitochondrial involvement in the radiation response of human hematopoietic stem cells (2013)
  • Author(s): M. Yamaguchi and I. Kashiwakura
  • Journal Title: c Volume: 8(7) Pages: e70503
  • Peer Reviewed
• [Presentation] 致死線量放射線ばく露マウスに対する C-Mpl作動薬の作用 (2013)
  • Author(s): 石川純也,廣内篤久,伊藤巧一,千葉満,中野学,門前暁,吉野浩教,羽澤勝治,中野光,山口平,田中公夫,柏倉幾郎
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
  • Year and Date: 2013-10-18
• [Presentation] 放射線曝露個体におけるマスト細胞への分化・増殖能の変化 (2013)
  • Author(s): 村上翔,廣内篤久,石川純也,山口平,柏倉幾郎
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
  • Year and Date: 2013-10-18
• [Remarks]
  • URL: http://www.hs.hirosaki-u.ac.jp/~kashiwakura/
• [Patent(Industrial Property Rights)] 放射線被ばく治療剤及び放射線被ばく治療方法 (2012)
  • Inventor(s): 柏倉幾郎,伊藤巧一,中野学,門前暁,千葉満,吉野浩教,廣内篤久
  • Industrial Property Rights Holder: 弘前大学
  • Industrial Property Rights Type: 用法特許
  • Industrial Property Number: 特願2012-250880
  • Filing Date: 2012-11-15