γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status
Abstract
:1. Introduction
2. Radiation Countermeasures: Radioprotectors, Mitigators and Therapeutics
3. U.S. Food and Drug Administration (U.S. FDA) Animal Efficacy Rule
4. Tocopherols and Tocotrienols: Members of the Vitamin E Family
5. Radioprotective Efficacy of γ-Tocotrienol (GT3) in the Mouse Model
5.1. Radioprotection against Hematopoietic Injury
5.2. Radioprotection against Gastrointestinal and Vascular Injuries
6. Cytokine Induction by GT3
6.1. Efficacy of GT3 Is Mediated through Granulocyte Colony-Stimulating Factor (G-CSF) Production in the Mouse Model
6.2. Mobilization of Mouse Progenitors by GT3-Induced G-CSF
7. Combination of GT3 with Other Agents for Enhancing Its Radioprotective Efficacy
7.1. Radioprotective Efficacy of GT3 and Pentoxifylline (PTX) Combination
7.2. Radioprotective Efficacy of GT3 and Amifostine Combination
7.3. Contribution of Thrombomodulin to GT3-Mediated Lethality Protection
8. Radioprotective Efficacy of GT3 in Nonhuman Primates (NHPs)
9. Mechanisms of Action
9.1. Antioxidant Properties of GT3
9.2. Effects of GT3 on 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) Reductase
9.3. Anti-Apoptotic Activity of GT3
10. Conclusions and Future Direction
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
ΔΨm | Mitochondrial membrane potential |
ARS | Acute radiation syndrome |
BH4 | Tetrahydrobiopterin |
CD | Cluster of differentiation molecule |
c-Kit+ | Stem cell factor positive |
DRF | Dose reduction factor |
Flk+ | Endothelial progenitor cell marker positive |
G-CSF | Granulocyte colony-stimulating factor |
GFRP | GTPCH feedback regulatory protein |
GI-ARS | Gastrointestinal acute radiation syndrome |
GRAS | Generally recognized as safe |
Gy | Gray |
GTPCH | Guanosine triphosphate cyclohydrolase 1 |
H-ARS | Hematopoietic acute radiation syndrome |
HMG-CoA | 3-Hydroxy-3-methylglutaryl-coenzyme A |
IL | Interleukin |
Lin− | Lineage negative |
IκBα | Inhibitor of κBα |
NF-κB | Nuclear factor-κB |
PTX | Pentoxifylline |
U.S. FDA | United States Food and Drug Administration |
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Singh, V.K.; Hauer-Jensen, M. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status. Int. J. Mol. Sci. 2016, 17, 663. https://doi.org/10.3390/ijms17050663
Singh VK, Hauer-Jensen M. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status. International Journal of Molecular Sciences. 2016; 17(5):663. https://doi.org/10.3390/ijms17050663
Chicago/Turabian StyleSingh, Vijay K., and Martin Hauer-Jensen. 2016. "γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status" International Journal of Molecular Sciences 17, no. 5: 663. https://doi.org/10.3390/ijms17050663