Analysis of the proteomic profiles in serum of mice treated with RadioDefender, a novel radiation medical countermeasure

Abstract Exposure to high doses of ionizing radiation arising from nuclear attacks or radiological emergencies can result in the development of acute radiation syndrome (ARS). Current treatments for ARS are limited to radiomitigators that help restore immune cell and platelet production along with bone marrow function. However, there are no radioprotectors available for use as a prophylaxis for military and first responders, although many are under investigation. RadioDefender is a candidate radioprotective agent derived from amifostine, a limited-use drug with radioprotective properties. Previous investigations in pre-treated human hematopoietic stem cells exposed to γ-radiation and mouse survival studies have shown that this candidate drug improves cell viability, supporting its potential for further development as a radioprotector. In this study, mice were treated with a single dose of either RadioDefender (250, 500, 600, or 700 mg/kg) or vehicle 24 hours prior to 9.2 Gy total-body γ-irradiation. Blood was collected at 30 days post-irradiation, and serum was isolated for proteomic analysis. As part of a larger investigation into the safety of RadioDefender, this study was performed to assess the efficacy of selected doses in combination with radiation exposure. Serum proteomic profiles of vehicle- and RadioDefender-treated animals were compared to healthy controls as an exploratory investigation of proteomic differences among animals surviving to 30 days post-irradiation. At 30 days post-irradiation, minimal differences in serum proteomic abundance were observed between any of the groups, suggesting that both irradiation- and drug-induced changes may have subsided by this time point.