Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome—A Concise Review

Höfer, Milan; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

doi:10.3390/molecules22050834

Cited by 14 publications

(6 citation statements)

References 75 publications

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“…Although the search for suitable, safe and effective radiation countermeasures was initiated more than half a century ago, it still represents a global challenge (Hofer et al 2017). Remedies for the accidental exposure of individuals, as well as mass populations, to high doses of ionizing radiation are scarce (Gaberman et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

Galal

Abdel-Rafei

Hasan

2018

Can. J. Physiol. Pharmacol.

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The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.

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Section: Discussionmentioning

confidence: 99%

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

Galal

Abdel-Rafei

Hasan

2018

Can. J. Physiol. Pharmacol.

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“…Several promising strategies are continuously being developed to improve radiotherapy. For instance, spatial dose fractionation, time dose fractionation, micro/mini-beam irradiation, heavy-ion irradiation [10,11,12,13,14,15,16,17], and application of normal cell radio-protectants [18,19] and/or tumor cell radiosensitizers [20] could already be used in practice and eventually combined. One of the radiosensitizing approaches proposed is to selectively potentiate radiation toxicity for tumor cells by metal nanoparticles [21,22,23,24,25,26,27,28].…”

Section: Introductionmentioning

confidence: 99%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.

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“…There is currently an increasing concern worldwide regarding potential radiation exposures, whether from clinical uses of radiation, nuclear accidents, or military/terrorist events, emphasizing the need for radiation countermeasure development (39)(40)(41)(42). Importantly, the development of effective countermeasures requires a complete understanding of the mechanisms of radiation-induced sequelae (17,(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Iron Deposition in the Bone Marrow and Spleen of Nonhuman Primates with Acute Radiation Syndrome

Day,

Rittase,

Slaven

et al. 2023

Radiation Research

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The risk of exposure to high levels of ionizing radiation from nuclear weapons or radiological accidents is an increasing world concern. Partial- or total-body exposure to high doses of radiation is potentially lethal through the induction of acute radiation syndrome (ARS). Hematopoietic cells are sensitive to radiation exposure; white blood cells primarily undergo apoptosis while red blood cells (RBCs) undergo hemolysis. Several laboratories demonstrated that the rapid hemolysis of RBCs results in the release of acellular iron into the blood. We recently demonstrated using a murine model of ARS after total-body irradiation (TBI) and the loss of RBCs, iron accumulated in the bone marrow and spleen, notably between 4–21 days postirradiation. Here, we investigated iron accumulation in the bone marrow and spleens from TBI nonhuman primates (NHPs) using histological stains. We observed trends in increased intracellular and extracellular brown pigmentation in the bone marrow after various doses of radiation, especially after 4–15 days postirradiation, but these differences did not reach significance. We observed a significant increase in Prussian blue-staining intracellular iron deposition in the spleen 13–15 days after 5.8–8.5 Gy of TBI. We observed trends of increased iron in the spleen after 30–60 days postirradiation, with varying doses of radiation, but these differences did not reach significance. The NHP model of ARS confirms our earlier findings in the murine model, showing iron deposition in the bone marrow and spleen after TBI.

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Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome—A Concise Review

Cited by 14 publications

References 75 publications

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Iron Deposition in the Bone Marrow and Spleen of Nonhuman Primates with Acute Radiation Syndrome

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