Radiation Protection by the Antioxidant Alpha-Tocopherol Succinate

摘要

Radiological terrorism and use of nuclear weapons are major concerns for national defense and homeland security. At low doses of radiation, the hazards from these scenarios may not be apparent immediately, but may result in late arising pathologies like cancer and pulmonary fibrosis. At high doses, the hazards vary from incapacitation due to nausea and diarrhea to mortality. Free radical species of oxygen, derived from the interaction of ionizing radiation with critical biological targets and with the aqueous cellular milieu, are implicated in these hazards. Scavengers of free radicals have been shown to be effective protectors from radiation damage. However, many of these protectors are either toxic or cannot be administered orally at doses that are effective. The data presented here indicate that alpha-tocopherol succinate (TS), a free radical scavenger, can be used as a radioprotector with low toxicity. Tocopherol succinate was dispersed in a vehicle containing polyethylene glycol- 400 (PEG) and given orally (PO) to male CD2F1 mice. About 22-24 hours later, they were irradiated at different doses of 60Co radiation at a dose rate of 0.6 Gy/min. To maximize the protection, different formulations of the vehicle were used. Mice were monitored for body weight and survival for 30 days. In vitro experiments were done to study the effects of TS on radiation-induced apoptosis of Jurkat cells (lymphoblastoid cell line) using flow cytometry. Although different formulations for solubilizing TS were used, oral formulations based on PEG were found to provide better protection than those based on oil emulsions. The best protection was obtained with a combination of PEG-400 and an emulsifier consisted of benzyl alcohol and ethyl alcohol.