Overview of Radiation-protective Agent Research and Prospects for the Future

Abstract

Since the discovery of X-rays in 1895, radioactivity and its effects on the body have led to the issue of radiation injury. Radiation-related casualties following exposure to a lethal dose of ionizing radiation show severe acute radiation syndromes (ARS) involving bone marrow death and gastrointestinal death. ARS causes a decrease in the peripheral blood cell count and such as severe ARS, the intake of appropriate medications is the most suitable initial treatment. Therefore, the development of effective radiation-protective agent is an important issue against radiological accidents and nuclear threats. In this review, the overview of radiation-protective/mitigative agent development against acute radiation effects (external exposure), as well as our research data, and the prospects for future research have been outlined.

Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome

“…We previously reported that treatment with the combination of domestically approved pharmaceutical drugs (e.g. G-CSF and RP) enhances the survival of mice exposed to lethal TBI [8][9][10].…”

“…The post-radiation treatment was performed within 2 h after TBI, and the TBI and non-TBI mice were administered different types of medications ( Table 1). The four types of medications were delivered in combinations of the following two commercially available drugs based on our previous reports [8][9][10]: recombinant human G-CSF Neutrogin® (Chugai Pharmaceutical, Tokyo, Japan) and human TPOR agonist RP (Romiplate®; Kyowa Hakko Kirin, Tokyo, Japan). G-CSF or RP was intraperitoneally administered once-daily for 3 or 4 times or once a week for up to 4 times, respectively.…”

“…The approval of cytokine use varies by country, and GM-CSFs, interleukin-3, and thrombopoietin (TPO), which are recommended as the principal therapeutic cytokines corresponding to ARS severity by the International Atomic Energy Agency [7], are not approved in Japan. We recently found that treatment with a combination of domestically approved drugs, such as a G-CSF (Neutrogin®) and the TPO receptor (TPOR) agonist romiplostim (RP; Romiplate®), rescues mice from lethal TBI [8][9][10]. Although the effectiveness of these drugs as a medical treatment for emergency radiation exposure has been reported, the necessary dosages reported were much higher than the clinically used dosages.…”

Mitigative Efficacy of the Clinical Dosage Administration of Granulocyte Colony-stimulating Factor and Romiplostim in Mice With Severe Acute Radiation Syndrome

“…MCMs that can address thrombocytopenia would likely have a positive effect on ARS patients when administered alone or in combination with a G-CSF, since the duration of severe thrombocytopenia appears to correlate with death to a greater extent than that of severe neutropenia and appears to be more clinically relevant to the survival in ARS [6]. The approval of cytokine use varies by country, and GM-CSFs, interleukin-3, and thrombopoietin (TPO), which are recommended as the principal therapeutic cytokines corresponding to ARS severity by the International Atomic Energy Agency [7], are not approved in Japan. We recently found that treatment with a combination of domestically approved drugs, such as a G-CSF (Neutrogin®) and the TPO receptor (TPOR) agonist romiplostim (RP; Romiplate®), rescues mice from lethal TBI [8][9][10].…”

Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome

“…On the other hand, the combination of G-CSF and MCMs that can address thrombocytopenia can be expected to improve the pancytopenia occurs in ARS patients, since the duration of severe thrombocytopenia appears to correlate with death to a greater extent than that of severe neutropenia and appears to be more clinically relevant to the survival in ARS [ 9 ]. The approval of cytokine use varies by country, and GM-CSFs, interleukin-3, and thrombopoietin (TPO), which are recommended as the principal therapeutic cytokines corresponding to ARS severity by the International Atomic Energy Agency [ 10 ], are not approved in Japan. We recently found that treatment with a combination of approved pharmaceutical drugs, such as a G-CSF (Neutrogin ® ) and the TPO receptor (TPOR) agonist romiplostim (RP; Romiplate ® ), rescues mice from lethal TBI [ 11 – 13 ].…”