Abstract: TH-PO0061
Can an Antioxidant/Anti-Inflammatory Compound Mitigate the Kidney Damage Caused by Galactic Cosmic Radiation on a 2.5-Year Simulated Mission to Mars?
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- D'Ambrosio, Viola, Universita Cattolica del Sacro Cuore, Rome, Italy
- Cohen, Eric P., NYU Langone Health, New York, New York, United States
- Li, Zhongwang, University College London, London, England, United Kingdom
- Nye, Emma, The Francis Crick Institute, London, England, United Kingdom
- Kiffer, Frederico, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
- Yun, Sanghee, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
- Roufosse, Candice A., Imperial College London, London, England, United Kingdom
- Eisch, Amelia J., The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
- Siew, Keith, University College London, London, England, United Kingdom
Background
Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation remain largely unexplored. We previously demonstrated that 6 months postexposure to a 33-ion GCR simulation (equivalent to a 2.5 year trip to Mars), both male and female mice exhibited increased proteinuria and 27% of female mice presented with thrombotic microangiopathy (TMA). Among the countermeasures tested, an Nrf2 activator, (CDDO)–methyl ester showed protection against oxidative stress.The aim of this work was to investigate whether the antioxidant/antiinflammatory compound (CDDO-EA) might mitigate the impact of 33-GCR.
Methods
A total of n=96 mature (6-month-old) C57BL/6J male and female mice were randomised to receive either CDDO-EA or vehicle control, and were subsequent exposed to either Sham-irradiation (Sham) or wholebody 33-GCR (0.75Gy). Animals were euthanised 6-months post exposure. H&E histological samples were prepared and whole slide images (WSI) taken of each kidney section for all animals. Glomeruli were segmented and extracted from the WSI using a custom A.I. script. Images were then inspected by four researchers (nephrologists, histologists and histopathologists) blinded to the group identity.
Results
In the original study, 3 of 11 female mice that were exposed to GCR and treated with vehicle presented with TMA. No TMA was detected in the GCR-exposed female mice that received CCDO, as well as in female mice that were Sham-irradiated with or without CDDO. No male mice showed TMA irrespective of Sham-irradiation, GCR exposure, CDDO or vehicle. Females were susceptible to TMA formation at 6 month post-GCR exposure and CDDO appeared to mitigate this effect. However, kidneys are late responding organs and longer post-exposure times are needed to establishedif this is a female-only phenomenon.
Conclusion
In conclusion, CDDO may be effective in mitigating the GCR-induced kidney damage. Advantages include the fact that CDDO is an already-approved FDA drug for ataxia (CDDO-EA) that has already been tested for chronic kidney disease. Further studies are needed, but our results upen up the possibility to drug repurposing of anti-oxidants as countermeasures against spaceflight induced kidney damage.
Acknowledgment
KS and this work was supported in part by the Royal Free Charity [Grant number 1088RD], Kidney Research UK [RP_017_20190306] and Wellcome Trust [Grant number 110282/Z/15/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.