title: Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation.
abstract: It is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents to reduce the radiation-related casualties. The present study aimed to establish an optimum therapeutic protocol using currently approved pharmaceutical drugs to increase the survival of victims exposed to lethal radiation. 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)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of γ-irradiation. On day 30 after irradiation, the condition of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells, hematopoietic progenitor cells and the expression of cell surface antigens. Approximately 10% of the untreated irradiated control mice survived for 21 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for five days immediately after irradiation led to a complete survival of the irradiated mice until day 30. However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at day 30. The hematological analyses showed that the numbers of almost all 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.
authors: Tokuhisa
authors: T
authors: Hirouchi
authors: Koichi
authors: K
authors: Ito
authors: Manabu
authors: M
authors: Nakano
authors: Satoru
authors: S
authors: Monzen
authors: Hironori
authors: H
authors: Yoshino
authors: Mitsuru
authors: M
authors: Chiba
authors: Masaharu
authors: M
authors: Hazawa
authors: Akira
authors: A
authors: Nakano
authors: Junya
authors: J
authors: Ishikawa
authors: Masaru
authors: M
authors: Yamaguchi
authors: Kimio
authors: K
authors: Tanaka
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan. ikashi@hirosaki-u.ac.jp.
authors: Ikuo
authors: I
authors: Kashiwakura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D011839:Radiation, Ionizing; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: C481270:Mpl protein, mouse; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D009277:Nandrolone; D013926:Thrombopoietin; C488777:romiplostim; D000077603:Nandrolone Decanoate