Abstract
The search for efficient radioprotective agents to protect from radiation-induced toxicity, due to planned or accidental radiation exposure, is still ongoing worldwide. Despite decades of research and development of widely different biochemical classes of natural and derivative compounds, a safe and effective radioprotector is largely unmet. In this comprehensive review, we evaluated the evidence for the radioprotective performance of classical thiols, vitamins, minerals, dietary antioxidants, phytochemicals, botanical and bacterial preparations, DNA-binding agents, cytokines, and chelators including adaptogens. Where radioprotection was demonstrated, the compounds have shown moderate dose modifying factors ranging from 1.1 to 2.7. To date, only few compounds found way to clinic with limited margin of dose prescription due to side effects. Most of these compounds (amifostine, filgratism, pegfilgrastim, sargramostim, palifermin, recombinant salmonella flagellin, Prussian blue, potassium iodide) act primarily via scavenging of free radicals, modulation of oxidative stress, signal transduction, cell proliferation or enhance radionuclide elimination. However, the gain in radioprotection remains hampered with low margin of tolerance. Future development of more effective radioprotectors requires an appropriate nontoxic compound, a model system and biomarkers of radiation exposure. These are important to test the effectiveness of radioprotection on physiological tissues during radiotherapy and field application in cases of nuclear eventualities.
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Abbreviations
- bFGF:
-
Beta fibroblast growth factors
- CD2F1:
-
Cluster of differentiations 2F1
- DMA:
-
(5-2-[2′-(3, 4-Dimethoxyphenyl)-5′-benzimidazolyl]
- DMF:
-
Dose modifying factor
- DTPA:
-
Diethylenetriaminepentaacetic acid
- FDA:
-
Food and Drug Administration
- G-CSF:
-
Granulocyte colony-stimulating factor
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- GPx:
-
Glutathione peroxidase
- GT3:
-
Gamma tocotrienol
- Gy:
-
Gray (dose of ionizing radiation)
- HMG-CoA:
-
3-Hydroxy-3-methyl-glutaryl-coenzyme A
- IL:
-
Interleukin
- MAP kinases:
-
Mitogen activated protein kinases
- MEA:
-
β-Mercaptoethyamine
- NF-kB:
-
Nuclear factor kappa beta
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- SQGD:
-
Semiquinone glucoside
- TBZ:
-
2-(4-Thiazolyl) benzimidazole
- TS:
-
Tocopherol succinate
- LD50:
-
Lethal dose for 50% killing
- TLR 2/6:
-
Toll-like receptor 2/6
- TNF-α:
-
Tumor necrosis factor-α
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Acknowledgements
We would like to extend sincere gratitude and appreciation to the Dr. B. Moftah, N. Al-Harbi, and S. Bin Judia for their supports, and Farah Yamak for helping in editing the manuscript.
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KM collected information and drafted the manuscript and GA conceived the review and critically revised and edited the content.
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This work was partially supported the National Science, Technology and Innovation Plan (NSTIP, KACST) Grants 12-MED2945-20 and 15-MED4114-20 (KFSHRC, RAC 2130-025 and 2170 005).
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The authors wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
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Mishra, K., Alsbeih, G. Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development. 3 Biotech 7, 292 (2017). https://doi.org/10.1007/s13205-017-0925-0
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DOI: https://doi.org/10.1007/s13205-017-0925-0