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Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development

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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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Correspondence to Ghazi Alsbeih.

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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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Data sharing is not applicable to this review manuscript as no datasets were generated or analyzed during the current study.

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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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