α-Tocopherol Succinate Protects Mice against Radiation-Induced Gastrointestinal Injury

The purpose of this study was to elucidate the role of alpha-tocopherol succinate (alpha-TS) in protecting mice from gastrointestinal syndrome induced by total-body irradiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of alpha-TS and exposed to different doses of Co-60 gamma radiation, and 30-day survival was monitored. Jejunum sections were analyzed for crypts and villi, PUMA (p53 upregulated modulator of apoptosis), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL). The crypt regeneration in irradiated mice was evaluated by 5-bromo-2-deoxyuridine (BrdU). Bacterial translocation from gut to heart, spleen and liver in alpha-TS-treated and irradiated mice was evaluated by bacterial culture on sheep blood agar, colistin-nalidixic acid, and xylose-lysine-desoxycholate medium. Our results demonstrate that alpha-TS enhanced survival in a significant number of mice irradiated with 9.5, 10, 11 and 11.5 Gy Co-60 gamma radiation when administered 24 h before radiation exposure. alpha-TS also protected the intestinal tissue of irradiated mice in terms of crypt and villus number, villus length and mitotic figures. TS treatment decreased the number of TUNEL- and PUMA-positive cells and increased the number of BrdU-positive cells in jejunum compared to vehicle-treated mice. Further, alpha-TS inhibited gut bacterial translocation to the heart, spleen and liver in irradiated mice. Our data suggest that alpha-TS protects mice from radiation-induced gastrointestinal damage by inhibiting apoptosis, promoting regeneration of crypt cells, and inhibiting translocation of gut bacteria. (C) 2012 by Radiation Research Society