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A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage
Military Medicine Research Unit, Test and Evaluation Command, Ground Self-Defense Force, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8566, Japan
Department of Immunology and Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8613, Japan
Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8613, Japan
* Author to whom correspondence should be addressed.
Received: 26 June 2013; in revised form: 9 September 2013 / Accepted: 13 September 2013 / Published: 27 September 2013
Abstract: The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage.
Keywords: ascorbic acid; abdominal radiation; citrulline; radiation-induced gastrointestinal damage; post-irradiation treatment with ascorbic acid
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Ito, Y.; Kinoshita, M.; Yamamoto, T.; Sato, T.; Obara, T.; Saitoh, D.; Seki, S.; Takahashi, Y. A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage. Int. J. Mol. Sci. 2013, 14, 19618-19635.
Ito Y, Kinoshita M, Yamamoto T, Sato T, Obara T, Saitoh D, Seki S, Takahashi Y. A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage. International Journal of Molecular Sciences. 2013; 14(10):19618-19635.
Ito, Yasutoshi; Kinoshita, Manabu; Yamamoto, Tetsuo; Sato, Tomohito; Obara, Takeyuki; Saitoh, Daizoh; Seki, Shuhji; Takahashi, Yukihiro. 2013. "A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage." Int. J. Mol. Sci. 14, no. 10: 19618-19635.