Although multiple radioprotectors are currently being investigated preclinically for efficacy and safety, few studies have investigated concomitant metabolic changes. This study examines the effects of
amifostine on the metabolic profiles in tissues of mice exposed to
cobalt-60 total-body gamma-radiation. Global metabolomic and lipidomic changes were analyzed using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in bone marrow, jejunum, and lung samples of
amifostine-treated and saline-treated control mice. Results demonstrate that radiation exposure leads to tissue specific metabolic responses that were corrected in part by treatment with
amifostine in a
drug-dose dependent manner. Bone marrow exhibited robust responses to radiation and was also highly responsive to protective effects of
amifostine, while jejunum and lung showed only modest changes. Treatment with
amifostine at 200 mg/kg prior to irradiation seemed to impart maximum survival benefit, while the lower dose of 50 mg/kg offered only limited survival benefit. These findings show that the administration of
amifostine causes metabolic shifts that would provide an overall benefit to
radiation injury and underscore the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of
amifostine. This approach may be helpful in identifying
biomarkers for radioprotective efficacy of
amifostine and other countermeasures under development.