THE POTENTIATION OF THE RADIOPROTECTIVE EFFICACY OF TWO MEDICAL COUNTERMEASURES, GAMMA-TOCOTRIENOL AND AMIFOSTINE, BY A COMBINATION PROPHYLACTIC MODALITY

Radiat Prot Dosimetry. 2016 Dec;172(1-3):302-310. doi: 10.1093/rpd/ncw223. Epub 2016 Aug 19.

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 Gy 60Co 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.

MeSH terms

  • Amifostine / administration & dosage*
  • Animals
  • Chromans / administration & dosage*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Combinations
  • Male
  • Mice
  • Radiation Dosage
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / prevention & control*
  • Radiation-Protective Agents / administration & dosage*
  • Survival Rate*
  • Treatment Outcome
  • Vitamin E / administration & dosage
  • Vitamin E / analogs & derivatives*
  • Whole-Body Irradiation

Substances

  • Chromans
  • Drug Combinations
  • Radiation-Protective Agents
  • Vitamin E
  • plastochromanol 8
  • Amifostine