α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury.
The purpose of this study was to elucidate the role of α-tocopherol succinate (α-TS) in protecting mice from gastrointestinal syndrome induced by total-body irradiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of α-TS and exposed to different doses of (60)Co γ 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 α-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 α-TS enhanced survival in a significant number of mice irradiated with 9.5, 10, 11 and 11.5 Gy (60)Co γ radiation when administered 24 h before radiation exposure. α-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, α-TS inhibited gut bacterial translocation to the heart, spleen and liver in irradiated mice. Our data suggest that α-TS protects mice from radiation-induced gastrointestinal damage by inhibiting apoptosis, promoting regeneration of crypt cells, and inhibiting translocation of gut bacteria.
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Ave, Bethesda, MD 20889-5603, USA. singh@afrri.usuhs.mil
Pankaj K
PK
Singh
Stephen Y
SY
Wise
Elizabeth J
EJ
Ducey
Oluseyi O
OO
Fatanmi
Thomas B
TB
Elliott
Vijay K
VK
Singh
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000517:prevention & control*; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000517:prevention & control*; D011835:Radiation Protection; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011859:Radiography; D015996:Survival Rate; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D011837:Radiation-Protective Agents; D024502:alpha-Tocopherol