Gamma-tocotrienol, a tocol antioxidant as a potent radioprotector.
OBJECTIVE
To assess the radioprotective potential of gamma-tocotrienol.


METHODS
To optimise its dose and time regimen, gamma-tocotrienol (GT3) was injected subcutaneously (SC) at different doses into male CD2F1 mice [LD(50/30) (lethal radiation dose that results in the mortality of 50% mice in 30 days) radiation dose of 8.6 Gy with vehicle]. The mice were given 10.5, 11 and 11.5 Gy cobalt-60 radiation, and 30-day survival-protection was determined. Time optimisation was done by SC administration of GT3 at different intervals before irradiation. Dose reduction factor (DRF) was determined by probit analysis using mortality as the end point at six radiation doses. Protection from radiation induced pancytopenia was determined by enumerating peripheral blood cells from mice given GT3 and irradiated at 7 Gy.


RESULTS
At an optimal dose of 200 mg/kg given SC 24 h before irradiation, GT3 had a DRF of 1.29. GT3 accelerated the recovery of total white blood cells, neutrophils, monocytes, platelets, and reticulocytes in irradiated mice, compared to vehicle-injected, irradiated controls.


CONCLUSIONS
GT3 is a radioprotectant having a higher DRF than any other tocols. The protection it provides close to the gastro-intestinal range indicate that GT3 can be considered as an ideal radioprotectant meriting further drug development stages for the ultimate use in humans.
Ghosh
Sanchita P
SP
Armed Forces Radiobiology Research Institute, USUHS, Bethesda, USA. ghosh@afrri.usuhs.mil
Kulkarni
Shilpa
S
Hieber
Kevin
K
Toles
Raymond
R
Romanyukha
Lyudmila
L
Kao
Tzu-Cheg
TC
Hauer-Jensen
Martin
M
Kumar
K Sree
KS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000528:radiation effects; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D011837:Radiation-Protective Agents; D014810:Vitamin E; C013649:plastochromanol 8