Hematopoietic recovery and amelioration of radiation-induced Lethality by the vitamin e isoform δ-tocotrienol

Merriline M. Satyamitra, Shilpa Kulkarni, Sanchita P. Ghosh, Conor P. Mullaney, Donald Condliffe, Venkataraman Srinivasan

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 60Co 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 (-â̂'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.

Original languageEnglish (US)
Pages (from-to)736-745
Number of pages10
JournalRadiation Research
Volume175
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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Tocotrienols
lethality
vitamins
Vitamins
Protein Isoforms
recovery
antioxidants
Radiation
dosage
irradiation
mice
radiation
protectors
tocopherol
macrophages
Antioxidants
nitric oxide
schedules
radiation sources
liver

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Hematopoietic recovery and amelioration of radiation-induced Lethality by the vitamin e isoform δ-tocotrienol. / Satyamitra, Merriline M.; Kulkarni, Shilpa; Ghosh, Sanchita P.; Mullaney, Conor P.; Condliffe, Donald; Srinivasan, Venkataraman.

In: Radiation Research, Vol. 175, No. 6, 06.2011, p. 736-745.

Research output: Contribution to journalArticle

Satyamitra, Merriline M. ; Kulkarni, Shilpa ; Ghosh, Sanchita P. ; Mullaney, Conor P. ; Condliffe, Donald ; Srinivasan, Venkataraman. / Hematopoietic recovery and amelioration of radiation-induced Lethality by the vitamin e isoform δ-tocotrienol. In: Radiation Research. 2011 ; Vol. 175, No. 6. pp. 736-745.
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