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

Michal Hofer,Daniel Depeš,Martin Falk,Zuzana Hoferová

doi:10.3390/molecules22050834

Abstract

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

Highlights

The search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, very few safe and effective radiation countermeasures for the most severe of these injuries, namely acute radiation syndrome (ARS), defined as ‘an acute illness caused by irradiation of the entire body by a high dose of penetrating ionizing radiation in a very short period of time [1], have been approved
This exception is represented by two granulocyte colony-stimulating factor (G-CSF)-based radiation countermeasures (Neupogen® and Neulasta® ) which have recently been approved by the United
As follows from the above summary of the findings on pharmacological modulation of ARS by combined drug treatment, this topic has required long-term attention. It can be deduced from the literature that, whereas in the years of the Cold War researchers focused their studies predominantly on the evaluation of “true radioprotectors”, i.e., chemical radioprotectors effective at pre-irradiation administration, current efforts are concentrated especially on compounds usable in therapeutic post-irradiation treatment approaches

Summary

Introduction

The search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, very few safe and effective radiation countermeasures for the most severe of these injuries, namely acute radiation syndrome (ARS), defined as ‘an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating ionizing radiation in a very short period of time (usually a matter of minutes) [1], have been approved. E.g., β-glucan and Broncho-Vaxom, shown here as examples of immunomodulators suitable for combined administration with amifostine for the treatment of ARS, possess no, or low, toxicity and are often commercially available Their mechanism of action enables them to be administered in both protective and therapeutic regimens. G-CSF for the treatment of ARS has been aimed especially at evaluating the efficacy of the combined pre-irradiation amifostine and post-irradiation G-CSF therapy In animal studies, this combination has been shown to be very effective [35,36], e.g., in a 30-day survival study, the LD50/30 values (radiation doses killing 50% of the experimental animals by day 30 after irradiation) for mice administered saline, G-CSF, amifostine, and amifostine + G-CSF have been reported to be 7.85 Gy, 8.30 Gy, 11.30 Gy, and 12.85 Gy, respectively [35].

Combinations

Findings

Discussion and Conclusions