Long-lasting Radioprotective Effects of a Combination of Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation

Abstract

To reduce radiation-related casualties, it is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents. 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 and aimed to estimate the long-lasting radioprotective activities of the present therapeutic protocol. The present combination of four drugs—recombinant human erythropoietin (EPO), granulocytecolony 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 γ-irradiation. On day 100 after irradiation, the health of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells and hematopoietic progenitor cells. Approximately 12.5% of the untreated irradiated control mice survived for 100 days. The combined administration of G-CSF, EPO and RP for 3 consecutive days and ND for 1 day immediately after irradiation led to an 87.5% survival of the irradiated mice until day 100. Hematological analyses showed that the number of most of the hematopoietic cells in the treated surviving mice had recovered to the levels of the nonirradiated mice on day 100. The present findings show that the combination of G-CSF, EPO, RP and ND may be a useful countermeasure for victims exposed to accidental lethal irradiation.