title: Hematopoietic Recovery and Amelioration of Radiation-Induced Lethality by the Vitamin E Isoform δ-Tocotrienol.
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.
authors: Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889, USA. satyamitra@afrri.usuhs.mil
authors: Merriline M
authors: MM
authors: Satyamitra
authors: Shilpa
authors: S
authors: Kulkarni
authors: Sanchita P
authors: SP
authors: Ghosh
authors: Conor P
authors: CP
authors: Mullaney
authors: Donald
authors: D
authors: Condliffe
authors: Venkataraman
authors: V
authors: Srinivasan
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D014916:Whole-Body Irradiation
chemical_list: D009573:Nitrites; D011837:Radiation-Protective Agents; D014810:Vitamin E; C082097:tocotrienol, delta