Tocopherol succinate: a promising radiation countermeasure.
Vitamin E is composed of a family of eight isomers known as tocols; consisting of four tocopherols and four tocotrienols that exist in four isomeric forms: alpha (alpha), beta (beta), gamma (gamma), and delta (delta). Earlier we have demonstrated the radioprotective efficacy of the succinate ester of alpha-tocopherol (alpha-tocopherol succinate, TS). CD2F1 mice were injected subcutaneously with 400 mg/kg of TS and irradiated with different doses of 60Co gamma-radiation to determine its radioprotective efficacy. The dose reduction factor (DRF) for TS was also determined. We also investigated effects of TS on cytokine production by multiplex Luminex and message by quantitative RT-PCR. Peripheral blood cells were enumerated from irradiated (3 and 7 Gy) and non-irradiated mice. TS significantly protected mice against lethal doses of 60Co gamma-radiation and the DRF was 1.28. TS stimulated granulocyte-colony stimulating factor (G-CSF) with a peak at 24 h after drug injection, and also stimulated G-CSF message as judged by RT-PCR in bone marrow cells at 12 and 24 h after injection. Further, pancytopenia studies revealed that TS significantly reduced thrombocytopenia, neutropenia, and monocytopenia. TS had no significant effect on lymphocytes indicating that it may be helpful only for the myeloid cell compartments. The stimulation of G-CSF by TS supports its effects on myeloid cell compartments. Our studies indicate that TS may be developed as a radioprotectant for humans against the potentially lethal effects of radiation exposure.
Singh
Vijay K
VK
Department of Radiation Biology, F. Edward Hebért School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-5603, USA. singh@afrri.usuhs.mil
Brown
Darren S
DS
Kao
Tzu-Cheg
TC
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D016207:Cytokines / Q000097:blood; D005720:Gamma Rays; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010198:Pancytopenia / Q000097:blood; D011832:Radiation Injuries / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D024505:Tocopherols / Q000008:administration & dosage
D003037:Cobalt Radioisotopes; D016207:Cytokines; D011837:Radiation-Protective Agents; D016179:Granulocyte Colony-Stimulating Factor; D024505:Tocopherols