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Article

Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice

1
Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, Washington, DC 20057, USA
2
Departments of Biochemistry, Molecular, and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA
3
Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
4
Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90024, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(1), 24; https://doi.org/10.3390/antiox14010024
Submission received: 25 November 2024 / Revised: 23 December 2024 / Accepted: 24 December 2024 / Published: 27 December 2024
(This article belongs to the Special Issue Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy)

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 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.
Keywords: radiation exposure; whole-body irradiation; partial-body irradiation; metabolomics; urine metabolomics; pathway analysis; machine learning; radiation effects; biomarkers radiation exposure; whole-body irradiation; partial-body irradiation; metabolomics; urine metabolomics; pathway analysis; machine learning; radiation effects; biomarkers

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MDPI and ACS Style

Li, Y.; Bansal, S.; Singh, B.; Jayatilake, M.M.; Klotzbier, W.; Boerma, M.; Lee, M.-H.; Hack, J.; Iwamoto, K.S.; Schaue, D.; et al. Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice. Antioxidants 2025, 14, 24. https://doi.org/10.3390/antiox14010024

AMA Style

Li Y, Bansal S, Singh B, Jayatilake MM, Klotzbier W, Boerma M, Lee M-H, Hack J, Iwamoto KS, Schaue D, et al. Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice. Antioxidants. 2025; 14(1):24. https://doi.org/10.3390/antiox14010024

Chicago/Turabian Style

Li, Yaoxiang, Shivani Bansal, Baldev Singh, Meth M. Jayatilake, William Klotzbier, Marjan Boerma, Mi-Heon Lee, Jacob Hack, Keisuke S. Iwamoto, Dörthe Schaue, and et al. 2025. "Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice" Antioxidants 14, no. 1: 24. https://doi.org/10.3390/antiox14010024

APA Style

Li, Y., Bansal, S., Singh, B., Jayatilake, M. M., Klotzbier, W., Boerma, M., Lee, M.-H., Hack, J., Iwamoto, K. S., Schaue, D., & Cheema, A. K. (2025). Distinct Urinary Metabolite Signatures Mirror In Vivo Oxidative Stress-Related Radiation Responses in Mice. Antioxidants, 14(1), 24. https://doi.org/10.3390/antiox14010024

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