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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Main Authors: 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
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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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.
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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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