Radioprotection and Radiomitigation: From the Bench to Clinical Practice

Abstract

The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed.

Mangosteen Hinders Gamma Radiation-Mediated Oxidative Stress and Liver Injury by Down-Regulating TNF-α/NF-κB and Pro-Fibrotic Factor TGF-β1 Inducing Inflammatory Signaling

“… 41 TNF has major immune functions in inflammation, cell proliferation control and division. 43 In our results the up-regulation of liver TNF-α, IL-6 and serum C-reactive protein (CRP) levels after exposure to 6 Gy of γ-irradiation might stimulate a feed forward loop in the NF-kB activation in Küpffer cells leading to secretion of IL-1α, TNF and also activation of quiescent hepatic stellate cells (HSCs) via stimulated TGF-β . Moreover, oxidative stress through its own increased TGF-β has driven apoptosis and enhanced hepatic damage cellular death, 44 which might explain radiation induced DNA fragmentation associated with boost of Caspase-3; as an indicator of apoptosis.…”

Acute Radiation Syndrome and the Microbiome: Impact and Review

“…Some improvement was noted in the group that consumed the prebiotic diet (reduction in days of diarrhea), suggesting that these dietary changes could lead to improved quality of life for these patients. Although the causal role of modulating microbiome by supplements to improve radiation injury resulting from accidental exposure to large doses is not as widely published, supplements are reported to protect gamma-irradiated mice ( Shimoi et al, 1994 ) and improve survival ( Satyamitra et al, 2011 ; Obrador et al, 2020 ). However, there are conflicting reports that underscore the need for caution in the use of all supplements without supporting data.…”

Could Polyphenols Really Be a Good Radioprotective Strategy?

“…In this context, several compounds have been described, but only amifostine, the S-phospho derivative of 2-[(3-aminopropyl)amino]ethanethiol, is approved as clinical radiation protector [ 11 ]. Other thiol-containing compounds, beyond nitroxides with superoxide dismutase (SOD)-like activity, hormone analogues, antibiotics, and phytochemicals, have been investigated as radioprotectors, whereas immunomodulators, probiotics, statins are explored as mitigator agents [ 12 ]. Specialized natural compounds are playing a key role in preclinical and clinical research, thanks to their anti-oxidant and anti-inflammatory efficacy that identifies them as promising agents in the field of radioprotection and radiomitigation.…”