Delta-Tocotrienol Protects Mice fromRadiation-Induced Gastrointestinal Injury

• Published in: Radiation research Vol. 180; no. 6; p. 649
• Main Authors: Li, Xiang Hong, Ghosh, Sanchita P, Ha, Cam T, Fu, Dadin, Elliott, Thomas B, Bolduc, David L, Villa, Vilmar, Whitnall, Mark H, Landauer, Michael R, Xiao, Mang
• Format: Journal Article
• Language: English
• Published: Lawrence Allen Press Inc 01-12-2013
• Subjects: Bone marrow; Irradiation; Survival; Translocation
• ISSN: 0033-7587; 1938-5404

We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiationinduced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy ^sup 60^Co total-body irradiation at a dose rate of 0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum sections were stained with hematoxylin and eosin and the surviving crypts in irradiated mice were counted. Apoptosis in intestinal epithelial cells was measured by terminal deoxy-nucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg) significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI. Administration of DT3 protected intestinal tissue, decreased apoptotic cells in jejunum and inhibited gut bacterial translocation in irradiated mice. Furthermore, DT3 significantly inhibited radiation-induced production of pro-inflammatory factors interleukin-1β and -6 and suppressed expression of protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis in mouse intestinal cells. Our data demonstrate that administration of DT3 protected mice from radiation-induced gastrointestinal system damage. [PUBLICATION ABSTRACT]