title: THE POTENTIATION OF THE RADIOPROTECTIVE EFFICACY OF TWO MEDICAL COUNTERMEASURES, GAMMA-TOCOTRIENOL AND AMIFOSTINE, BY A COMBINATION PROPHYLACTIC MODALITY.
abstract: This study was designed to evaluate the possible potentiation of survival protection afforded by relatively low-dose amifostine prophylaxis against total body irradiation in combination with a protective, less toxic agent, gamma-tocotrienol (GT3). Mice were administered amifostine and/or GT3, then exposed to 9.2 Gy60Co γ-irradiation and monitored for survival for 30 days. To investigate cytokine stimulation, mice were administered amifostine or GT3; serum samples were collected and analyzed for cytokines. Survival studies show single treatments of GT3 or amifostine significantly improved survival, compared to the vehicle, and combination treatments resulted in significantly higher survival compared to single treatments. In vivo studies with GT3 confirmed prior work indicating GT3 induces granulocyte colony-stimulating factor (G-CSF). This approach, the prophylactic combination of amifostine and GT3, which act through different mechanisms, shows promise and should be investigated further as a potential countermeasure for acute radiation syndrome.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine 'America's Medical School', Services University of the Health Sciences , Bethesda, MD, USA vijay.singh@usuhs.edu.|Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine 'America's Medical School', Services University of the Health Sciences , Bethesda, MD, USA.|Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine 'America's Medical School', Services University of the Health Sciences , Bethesda, MD, USA.|Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine 'America's Medical School', Services University of the Health Sciences , Bethesda, MD, USA.|Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Newman
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine 'America's Medical School', Services University of the Health Sciences , Bethesda, MD, USA.|Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Patricia L P
authors.initials: PL
authors.lastname: Romaine
authors.affiliation: Tech Micro Services , Bethesda, MD, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
mesh_terms: D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D002839:Chromans / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D015996:Survival Rate; D016896:Treatment Outcome; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
chemical_list: D002839:Chromans; D004338:Drug Combinations; D011837:Radiation-Protective Agents; D014810:Vitamin E; C013649:plastochromanol 8; D004999:Amifostine