Hematopoietic Recovery and Amelioration of Radiation-Induced Lethality by the Vitamin E Isoform δ-Tocotrienol

Radiat Res. 2011 Jun;175(6):736-45. doi: 10.1667/RR2460.1. Epub 2011 Mar 24.

Abstract

δ-Tocotrienol (DT3), a vitamin E isoform, is associated with strong antioxidant and immunomodulatory properties. We confirmed the potent antioxidant activity in membrane systems and showed that DT3 is an effective radiation protector and mitigator. DT3 (4 μM, P < 0.001) inhibited lipid peroxidation in mouse liver microsomes and nitric oxide (NO) formation (20 μM DT3, P < 0.01) in RAW264.7 cells, a murine alveolar macrophage line. In CD2F1 mice exposed to lethal total-body radiation from a (60)Co γ-radiation source, a single subcutaneous (s.c.) injection of DT3 before or after irradiation produced a significant increase in 30-day survival. DT3 was effective from 18.75 to 300 mg/kg (--24 h, P < 0.001). A single dose of 150 or 300 mg/kg DT3 given 24 h before irradiation (radioprotection) resulted in dose reduction factors (DRFs) of 1.19 and 1.27, respectively (P < 0.001). Further, DT3 reduced radiation lethality when administered 2, 6 or 12 h after irradiation, and 150 mg/kg DT3 administered 2 h after exposure conferred a DRF of 1.1 (mitigation). The optimum schedule of 300 mg/kg DT3 24 h prior to 7 Gy significantly reduced pancytopenia compared to irradiated controls (P < 0.05). The large therapeutic potential of and multi-lineage hematopoietic recovery for DT3 warrants further studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Hematopoiesis / drug effects
  • Hematopoiesis / radiation effects*
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Microsomes, Liver / metabolism
  • Nitrites / metabolism
  • Radiation-Protective Agents / pharmacology*
  • Time Factors
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology
  • Whole-Body Irradiation

Substances

  • Nitrites
  • Radiation-Protective Agents
  • Vitamin E
  • tocotrienol, delta