# Radiomitigators: Breakthroughs in Post-Radiation Recovery

## TL;DR

This review explores radiomitigators, which help reduce radiation damage after exposure, focusing on their mechanisms and potential for improving recovery in medical and emergency settings.

## Contribution

The paper provides a comprehensive overview of radiomitigators, emphasizing their translational potential and mechanisms of action for post-radiation recovery.

## Key findings

- Radiomitigators can attenuate radiation-induced damage when administered post-exposure.
- Key mechanisms include reducing oxidative stress and enhancing DNA repair pathways.
- Clinical translation challenges and strategies for optimizing radiomitigators are identified.

## Abstract

Ionizing radiation (IR) exposure poses a significant biomedical challenge in clinical, occupational, and emergency contexts, highlighting the urgent need for effective medical countermeasures against acute radiation syndrome (ARS) and delayed effects of radiation exposure (DEARE). Depending on the timing of administration, radiation countermeasures are classified as radioprotectors, radiomitigators, or therapeutics. Among these, radiomitigators offer a critical advantage by attenuating IR-induced damage when administered after exposure, thereby expanding their applicability in unanticipated radiation incidents. This review provides an overview of the pathophysiological mechanisms underlying IR-induced injury and summarizes the current FDA-approved radiation countermeasures. It then focuses on radiomitigators that have demonstrated efficacy in preclinical animal models, together with available evidence from clinical studies, emphasizing their translational potential for both emergency preparedness and oncological settings. We examine routes of administration and key mechanisms of action, including modulation of oxidative and nitrosative stress, enhancement of DNA damage response pathways, preservation of mitochondrial function, regulation of inflammatory and immune signaling, attenuation of fibrotic remodeling, maintenance of vascular integrity, and promotion of tissue regeneration and repair. Finally, challenges associated with clinical translation and strategies to optimize radiomitigators for the management of radiation-induced injury are discussed. By integrating these insights and consolidating existing knowledge, this review aims to guide basic and clinical research toward more effective radiomitigative strategies and combination therapies to improve survival, limit tissue damage, and preserve long-term quality of life in individuals exposed to IR.