Metabolomics identifies plasma biomarkers of localized radiation injury
Abstract A radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for i...
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Nature Portfolio
2025-01-01
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Online Access: | https://doi.org/10.1038/s41598-025-85717-5 |
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author | Lucie Ancel Stéphane Grison Olivier Gabillot Jules Gueguen Ljubica Svilar Bernard Le Guen Gaëtan Gruel Marc Benderitter Jean-Charles Martin Maâmar Souidi Radia Tamarat Stéphane Flamant Mohamed Amine Benadjaoud |
author_facet | Lucie Ancel Stéphane Grison Olivier Gabillot Jules Gueguen Ljubica Svilar Bernard Le Guen Gaëtan Gruel Marc Benderitter Jean-Charles Martin Maâmar Souidi Radia Tamarat Stéphane Flamant Mohamed Amine Benadjaoud |
author_sort | Lucie Ancel |
collection | DOAJ |
description | Abstract A radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for improving medical care efficiency. This preclinical study aims to identify circulating metabolites as biomarkers associated with LRI using a C57BL/6J mouse model of hind limb irradiation. More precisely, two independent mice cohorts were used to conduct a broad-spectrum profiling study followed by a suspect screening analysis performed on plasma metabolites by mass spectrometry. An integrative analysis was conducted through a multi-block sparse partial least square discriminant analysis (sPLS-DA) to establish multi-scale correlations between specific metabolites levels and biological, physiological (injury severity), and functional parameters (skin perfusion). The identified biomarker signature consists in a 6-metabolite panel including putrescine, uracil, 2,3-dihydroxybenzoate, 3-hydroxybenzoate, L-alanine and pyroglutamate, that can discriminate mice according to radiation dose and injury severity. Our results demonstrate relevant molecular signature associated with LRI in mice and support the use of plasma metabolites as suitable molecular biomarkers for LRI prognosis and diagnosis. |
format | Article |
id | doaj-art-b47f8c0bdbe641fb835ad02f1bad07e0 |
institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-01-01 |
publisher | Nature Portfolio |
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spelling | doaj-art-b47f8c0bdbe641fb835ad02f1bad07e02025-01-19T12:20:17ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85717-5Metabolomics identifies plasma biomarkers of localized radiation injuryLucie Ancel0Stéphane Grison1Olivier Gabillot2Jules Gueguen3Ljubica Svilar4Bernard Le Guen5Gaëtan Gruel6Marc Benderitter7Jean-Charles Martin8Maâmar Souidi9Radia Tamarat10Stéphane Flamant11Mohamed Amine Benadjaoud12Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SESANE/LRToxInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccCentre Cardiovasculaire et Nutrition (C2VN), CRIBIOM, Aix Marseille UniversitéÉlectricité de France (EDF)Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMEDInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTEC2VN, INRAE, INSERM, BIOMET, Aix Marseille UniversitéInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTEInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccInstitut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAccAbstract A radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for improving medical care efficiency. This preclinical study aims to identify circulating metabolites as biomarkers associated with LRI using a C57BL/6J mouse model of hind limb irradiation. More precisely, two independent mice cohorts were used to conduct a broad-spectrum profiling study followed by a suspect screening analysis performed on plasma metabolites by mass spectrometry. An integrative analysis was conducted through a multi-block sparse partial least square discriminant analysis (sPLS-DA) to establish multi-scale correlations between specific metabolites levels and biological, physiological (injury severity), and functional parameters (skin perfusion). The identified biomarker signature consists in a 6-metabolite panel including putrescine, uracil, 2,3-dihydroxybenzoate, 3-hydroxybenzoate, L-alanine and pyroglutamate, that can discriminate mice according to radiation dose and injury severity. Our results demonstrate relevant molecular signature associated with LRI in mice and support the use of plasma metabolites as suitable molecular biomarkers for LRI prognosis and diagnosis.https://doi.org/10.1038/s41598-025-85717-5MetaboliteIonizing radiationMolecular biomarkersLocalized radiation injury |
spellingShingle | Lucie Ancel Stéphane Grison Olivier Gabillot Jules Gueguen Ljubica Svilar Bernard Le Guen Gaëtan Gruel Marc Benderitter Jean-Charles Martin Maâmar Souidi Radia Tamarat Stéphane Flamant Mohamed Amine Benadjaoud Metabolomics identifies plasma biomarkers of localized radiation injury Scientific Reports Metabolite Ionizing radiation Molecular biomarkers Localized radiation injury |
title | Metabolomics identifies plasma biomarkers of localized radiation injury |
title_full | Metabolomics identifies plasma biomarkers of localized radiation injury |
title_fullStr | Metabolomics identifies plasma biomarkers of localized radiation injury |
title_full_unstemmed | Metabolomics identifies plasma biomarkers of localized radiation injury |
title_short | Metabolomics identifies plasma biomarkers of localized radiation injury |
title_sort | metabolomics identifies plasma biomarkers of localized radiation injury |
topic | Metabolite Ionizing radiation Molecular biomarkers Localized radiation injury |
url | https://doi.org/10.1038/s41598-025-85717-5 |
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