THE POTENTIATION OF THE RADIOPROTECTIVE EFFICACY OF TWO MEDICAL COUNTERMEASURES, GAMMA-TOCOTRIENOL AND AMIFOSTINE, BY A COMBINATION PROPHYLACTIC MODALITY

Overview

Journal Radiat Prot Dosimetry

Publisher Oxford University Press

Date 2016 Aug 21

PMID 27542813

Citations 24

Authors

Vijay K Singh

Oluseyi O Fatanmi

Stephen Y Wise

Victoria L Newman

Patricia L P Romaine

Thomas M Seed

Affiliations

Soon will be listed here.

Abstract

This study was designed to evaluate the possible potentiation of survival protection afforded by relatively low-dose amifostine prophylaxis against total body irradiation in combination with a protective, less toxic agent, gamma-tocotrienol (GT3). Mice were administered amifostine and/or GT3, then exposed to 9.2 Gy Co γ-irradiation and monitored for survival for 30 days. To investigate cytokine stimulation, mice were administered amifostine or GT3; serum samples were collected and analyzed for cytokines. Survival studies show single treatments of GT3 or amifostine significantly improved survival, compared to the vehicle, and combination treatments resulted in significantly higher survival compared to single treatments. In vivo studies with GT3 confirmed prior work indicating GT3 induces granulocyte colony-stimulating factor (G-CSF). This approach, the prophylactic combination of amifostine and GT3, which act through different mechanisms, shows promise and should be investigated further as a potential countermeasure for acute radiation syndrome.

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References

MacVittie T, Farese A . Cytokine-based treatment of radiation injury: potential benefits after low-level radiation exposure. Mil Med. 2002; 167(2 Suppl):68-70. View

Krivokrysenko V, Shakhov A, Singh V, Bone F, Kononov Y, Shyshynova I . Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther. 2012; 343(2):497-508. PMC: 3477210. DOI: 10.1124/jpet.112.196071. View

Pellmar T, Rockwell S . Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res. 2004; 163(1):115-23. DOI: 10.1667/rr3283. View

KLIGERMAN M, Glover D, Turrisi A, Norfleet A, Yuhas J, Coia L . Toxicity of WR-2721 administered in single and multiple doses. Int J Radiat Oncol Biol Phys. 1984; 10(9):1773-6. DOI: 10.1016/0360-3016(84)90547-9. View

Landauer M, Davis H, Dominitz J, Weiss J . Comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: WR-2721, cysteamine, diethyldithiocarbamate, and N-acetylcysteine. Pharmacol Ther. 1988; 39(1-3):97-100. DOI: 10.1016/0163-7258(88)90046-0. View

Singh V, Beattie L, Seed T . Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures. J Radiat Res. 2013; 54(6):973-88. PMC: 3823775. DOI: 10.1093/jrr/rrt048. View

van der Vijgh W, Peters G . Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (Ethyol): preclinical aspects. Semin Oncol. 1994; 21(5 Suppl 11):2-7. View

Patchen M, MacVittie T, Solberg B, Souza L . Therapeutic administration of recombinant human granulocyte colony-stimulating factor accelerates hemopoietic regeneration and enhances survival in a murine model of radiation-induced myelosuppression. Int J Cell Cloning. 1990; 8(2):107-22. DOI: 10.1002/stem.5530080204. View

Kulkarni S, Singh P, Ghosh S, Posarac A, Singh V . Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of gamma-tocotrienol, a promising radiation countermeasure. Cytokine. 2013; 62(2):278-85. DOI: 10.1016/j.cyto.2013.03.009. View

10.

Singh V, Kulkarni S, Fatanmi O, Wise S, Newman V, Romaine P . Radioprotective Efficacy of Gamma-Tocotrienol in Nonhuman Primates. Radiat Res. 2016; 185(3):285-98. DOI: 10.1667/RR14127.1. View

11.

Singh V, Fatanmi O, Singh P, Whitnall M . Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation. Cytokine. 2012; 58(3):406-14. DOI: 10.1016/j.cyto.2012.03.011. View

12.

Singh P, Wise S, Ducey E, Brown D, Singh V . Radioprotective efficacy of tocopherol succinate is mediated through granulocyte-colony stimulating factor. Cytokine. 2011; 56(2):411-21. DOI: 10.1016/j.cyto.2011.08.016. View

13.

Singh V, Yadav V . Role of cytokines and growth factors in radioprotection. Exp Mol Pathol. 2005; 78(2):156-69. DOI: 10.1016/j.yexmp.2004.10.003. View

14.

Kumar K, Raghavan M, Hieber K, Ege C, Mog S, Parra N . Preferential radiation sensitization of prostate cancer in nude mice by nutraceutical antioxidant gamma-tocotrienol. Life Sci. 2006; 78(18):2099-104. DOI: 10.1016/j.lfs.2005.12.005. View

15.

MacVittie T, Monroy R, Patchen M, Souza L . Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Biol. 1990; 57(4):723-36. DOI: 10.1080/09553009014550891. View

16.

Miller R, Murley J, Grdina D . Metformin exhibits radiation countermeasures efficacy when used alone or in combination with sulfhydryl containing drugs. Radiat Res. 2014; 181(5):464-70. PMC: 4080797. DOI: 10.1667/RR13672.1. View

17.

Weiss J . Pharmacologic approaches to protection against radiation-induced lethality and other damage. Environ Health Perspect. 1998; 105 Suppl 6:1473-8. PMC: 1469917. DOI: 10.1289/ehp.97105s61473. View

18.

Nagy V . Accuracy considerations in EPR dosimetry. Appl Radiat Isot. 2000; 52(5):1039-50. DOI: 10.1016/s0969-8043(00)00052-x. View

19.

Sen C, Khanna S, Roy S . Tocotrienols: Vitamin E beyond tocopherols. Life Sci. 2006; 78(18):2088-98. PMC: 1790869. DOI: 10.1016/j.lfs.2005.12.001. View

20.

Singh V, Newman V, Berg A, MacVittie T . Animal models for acute radiation syndrome drug discovery. Expert Opin Drug Discov. 2015; 10(5):497-517. DOI: 10.1517/17460441.2015.1023290. View