title: Delta-tocotrienol protects mice from radiation-induced gastrointestinal injury.
abstract: 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 radiation-induced 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 (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 deoxynucleotidyl 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.
authors.affiliation: a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Xiang Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Sanchita P
authors.initials: SP
authors.lastname: Ghosh
authors.forename: Cam T
authors.initials: CT
authors.lastname: Ha
authors.forename: Dadin
authors.initials: D
authors.lastname: Fu
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.forename: David L
authors.initials: DL
authors.lastname: Bolduc
authors.forename: Vilmar
authors.initials: V
authors.lastname: Villa
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
authors.forename: Michael R
authors.initials: MR
authors.lastname: Landauer
authors.forename: Mang
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D018988:Bacterial Translocation / Q000187:drug effects / Q000528:radiation effects; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004847:Epithelial Cells / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects / Q000293:injuries* / Q000528:radiation effects; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D017785:Photons / Q000009:adverse effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016019:Survival Analysis; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D003037:Cobalt Radioisotopes; D008840:Microfilament Proteins; D011837:Radiation-Protective Agents; C485645:TWF2 protein, mouse; D014810:Vitamin E; C082097:tocotrienol, delta; D011505:Protein-Tyrosine Kinases