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Antioxidants
Special Issues
Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy
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Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1726

Special Issue Editor

Prof. Dr. Jean Paul Jay-Gerin

E-Mail Website
Guest Editor
Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Interests: water radiolysis; early events in radiobiology; free radicals; radioprotectors/antioxidants; FLASH radiobiology/radiotherapy; Monte Carlo multi-track chemistry simulations; water chemistry in small modular reactors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiation therapy (RT) is essential in modern cancer treatment. It uses ionizing radiation to target and destroy cancer cells as a core element of oncological care. A major challenge in RT is delivering effective cancer-killing doses while reducing severe side effects to nearby healthy tissues. To address this, clinical radiotherapy has shifted towards ultra-high dose rate irradiation, known as FLASH irradiation. This method significantly lessens damage to healthy tissues while preserving the anti-tumor effectiveness of standard clinical dose rates, which are much slower than FLASH rates.

Multiple preclinical studies, both in vitro and in vivo using cell cultures and animal models, primarily with electron linear accelerators, support the evidence that FLASH-RT can spare normal tissues, challenging traditional radiobiology principles. Recently, the protective benefits of FLASH-RT have been shown using megavoltage photons, cyclotron-based protons, helium, and carbon ions, expanding its potential applications significantly.

The molecular mechanisms that differentiate tumor and normal tissue responses to FLASH-RT remain unclear. Clarifying these mechanisms is essential for the clinical application of the FLASH effect. This Special Issue aims to gather papers that offer the latest insights into these processes, with a particular emphasis on radiation-induced oxidative stress, the production of reactive oxygen and nitrogen species, and the role of antioxidants in modulating these effects.

Prof. Dr. Jean Paul Jay-Gerin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • radiobiology and radiotherapy
  • ultra-high dose rate irradiation and the FLASH effect
  • molecular and cellular mechanisms
  • radiation-induced oxidative stress
  • reactive oxygen and nitrogen species
  • inflammatory processes
  • antioxidants and radioprotectors
  • pulse radiolysis
  • kinetics
  • physicochemical and biological processes
  • DNA damage
  • role of oxygen and the oxygen depletion hypothesis
  • modeling and experimental
  • FLASH particle therapy

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Published Papers (2 papers)

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22 pages, 1811 KiB  
Article
Oxygen Depletion and the Role of Cellular Antioxidants in FLASH Radiotherapy: Mechanistic Insights from Monte Carlo Radiation-Chemical Modeling
by Israth Rabeya, Jintana Meesungnoen and Jean-Paul Jay-Gerin
Antioxidants 2025, 14(4), 406; https://doi.org/10.3390/antiox14040406 - 28 Mar 2025
Viewed by 459
Abstract
FLASH radiotherapy is a novel irradiation modality that employs ultra-high mean dose rates exceeding 40–150 Gy/s, far surpassing the typical ~0.03 Gy/s used in conventional radiotherapy. This advanced technology delivers high doses of radiation within milliseconds, effectively targeting tumors while minimizing damage to [...] Read more.
FLASH radiotherapy is a novel irradiation modality that employs ultra-high mean dose rates exceeding 40–150 Gy/s, far surpassing the typical ~0.03 Gy/s used in conventional radiotherapy. This advanced technology delivers high doses of radiation within milliseconds, effectively targeting tumors while minimizing damage to the surrounding healthy tissues. However, the precise mechanism that differentiates responses between tumor and normal tissues is not yet understood. This study primarily examines the ROD hypothesis, which posits that oxygen undergoes transient radiolytic depletion following a radiation pulse. We developed a computational model to investigate the effects of dose rate on radiolysis in an aqueous environment that mimics a confined cellular space subjected to instantaneous pulses of energetic protons. This study employed the multi-track chemistry Monte Carlo simulation code, IONLYS-IRT, which has been optimized to model this radiolysis in a homogeneous and aerated medium. This medium is composed primarily of water, alongside carbon-based biological molecules (RH), radiation-induced bio-radicals (R●), glutathione (GSH), ascorbate (AH−), nitric oxide (●NO), and α-tocopherol (TOH). Our model closely monitors the temporal variations in these components, specifically focusing on oxygen consumption, from the initial picoseconds to one second after exposure. Simulations reveal that cellular oxygen is transiently depleted primarily through its reaction with R● radicals, consistent with prior research, but also with glutathione disulfide radical anions (GSSG●−) in roughly equal proportions. Notably, we show that, contrary to some reports, the peroxyl radicals (ROO●) formed are not neutralized by recombination reactions. Instead, these radicals are rapidly neutralized by antioxidants present in irradiated cells, with AH− and ●NO proving to be the most effective in preventing the propagation of harmful peroxidation chain reactions. Moreover, our model identifies a critical dose rate threshold below which the FLASH effect, as predicted by the ROD hypothesis, cannot fully manifest. By comparing our findings with existing experimental data, we determine that the ROD hypothesis alone cannot entirely explain the observed FLASH effect. Our findings indicate that antioxidants might significantly contribute to the FLASH effect by mitigating radiation-induced cellular damage and, in turn, enhancing cellular radioprotection. Additionally, our model lends support to the hypothesis that transient oxygen depletion may partially contribute to the FLASH effect observed in radiotherapy. However, our findings indicate that this mechanism alone is insufficient to fully explain the phenomenon, suggesting the involvement of additional mechanisms or factors and warranting further investigation. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy)
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16 pages, 3330 KiB  
Article
Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice
by Yaoxiang Li, Shivani Bansal, Baldev Singh, Meth M. Jayatilake, William Klotzbier, Marjan Boerma, Mi-Heon Lee, Jacob Hack, Keisuke S. Iwamoto, Dörthe Schaue and Amrita K. Cheema
Antioxidants 2025, 14(1), 24; https://doi.org/10.3390/antiox14010024 - 27 Dec 2024
Viewed by 730
Abstract
Exposure to ionizing radiation disrupts metabolic pathways and causes oxidative stress, which can lead to organ damage. In this study, urinary metabolites from mice exposed to high-dose and low-dose whole-body irradiation (WBI HDR, WBI LDR) or partial-body irradiation (PBI BM2.5) were analyzed using [...] Read more.
Exposure to ionizing radiation disrupts metabolic pathways and causes oxidative stress, which can lead to organ damage. In this study, urinary metabolites from mice exposed to high-dose and low-dose whole-body irradiation (WBI HDR, WBI LDR) or partial-body irradiation (PBI BM2.5) were analyzed using targeted and untargeted metabolomics approaches. Significant metabolic changes particularly in oxidative stress pathways were observed on Day 2 post-radiation. By Day 30, the WBI HDR group showed persistent metabolic dysregulation, while the WBI LDR and PBI BM2.5 groups were similar to control mice. Machine learning models identified metabolites that were predictive of the type of radiation exposure with high accuracy, highlighting their potential use as biomarkers for radiation damage and oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy)
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