{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T08:31:36Z","timestamp":1793435496345,"version":"4.5.0"},"reference-count":56,"publisher":"Radiation Research Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2022,2,16]]},"abstract":"<jats:p>Radiation-induced esophageal injury (RIEI) is a major dose-limiting complication of radiotherapy, especially for esophageal and thoracic cancers. RIEI is a multi-factorial and multi-step process, which is regulated by a complex network of DNA, RNA, protein and metabolite. However, it is unclear which esophageal metabolites are altered by ionizing radiation and how these changes affect RIEI progression. In this work, we established a rat model of RIEI with 0\u201340 Gy X-ray irradiation. Esophageal irradiation using \u226525 Gy induced significant changes to rats, such as body weight, food intake, water intake and esophageal structure. The metabolic changes and related pathways of rat esophageal metabolites were investigated by liquid chromatography-mass spectrometry (LC-MS). One hundred eighty metabolites showed an up-regulation in a dose-dependent manner (35 Gy \u2265 25 Gy &gt; controls), and 199 metabolites were downregulated with increasing radiation dose (35 Gy \u2264 25 Gy &lt; controls). The KEGG analysis showed that ionizing radiation seriously disrupted multiple metabolic pathways, and arachidonic acid metabolism was the most significantly enriched pathway. 20 metabolites were dysregulated in arachidonic acid metabolism, including up-regulation of five prostaglandins (PGA2, PGJ2, PGD2, PGH2, and PGI2) in 25 or 35 Gy groups. Cyclooxygenase-2 (COX-2), the key enzyme in catalyzing the biosynthesis of prostaglandins from arachidonic acid, was highly expressed in the esophagus of irradiated rats. Additionally, receiver operating characteristic (ROC) curve analysis revealed that PGJ2 may serve as a promising tissue biomarker for RIEI diagnosis. Taken together, these findings indicate that ionizing radiation induces esophageal metabolic alterations, which advance our understanding of the pathophysiology of RIEI from the perspective of metabolism.<\/jats:p>","DOI":"10.1667\/rade-20-00240.1","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T16:31:52Z","timestamp":1645029112000},"page":"480-490","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Profiling Implicates a Critical Role of Cyclooxygenase-2-Mediated Arachidonic Acid Metabolism in Radiation-Induced Esophageal Injury in Rats"],"prefix":"10.1667","volume":"197","author":[{"given":"Wenling","family":"Tu","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Feng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Wu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanghua","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Shao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Tang","sequence":"additional","affiliation":[{"name":"West China Second University Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Shi","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"V Bar-Ad, B Leiby, M Witek, et al.  \"Am J Clin Oncol.\"  37, \"Treatment-related acute esophagitis for patients with locoregionally advanced non-small cell lung cancer treated with involved-field radiotherapy and concurrent chemotherapy.\" (2014)","DOI":"10.1097\/COC.0b013e31827de7a2"},{"key":"2","doi-asserted-by":"crossref","unstructured":"D Murro  and S Jakate  \"Arch Pathol Lab Med.\"  139, \"Radiation esophagitis.\" 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Wishart,  \"Physiol Rev.\"  99, \"Metabolomics for investigating physiological and pathophysiological processes.\" (2019)","DOI":"10.1152\/physrev.00035.2018"},{"key":"30","doi-asserted-by":"crossref","unstructured":"RK Azad  and V Shulaev  \"Brief Bioinform.\"  20, \"Metabolomics technology and bioinformatics for precision medicine.\" (2019)","DOI":"10.1093\/bib\/bbx170"},{"key":"31","doi-asserted-by":"crossref","unstructured":"L Li, P Krznar, A Erban, et al.  \"Diabetes.\"  68, \"Metabolomics Identifies a biomarker revealing in vivo loss of functional \u03b2-cell mass before diabetes onset.\" (2019)","DOI":"10.2337\/db19-0131"},{"key":"32","doi-asserted-by":"crossref","unstructured":"IL Jackson, PT Xu, G Nguyen, et al.  \"Health Phys.\"  106, \"Characterization of the dose response relationship for lung injury following acute radiation exposure in three well-established murine strains: Developing an interspecies bridge to link animal models with human lung.\" 48 (2014)","DOI":"10.1097\/HP.0b013e3182a32ccf"},{"key":"33","doi-asserted-by":"crossref","unstructured":"AL DiCarlo, AC Bandremer, BA Hollingsworth, et al.  \"Radiat Res.\"  194, \"Cutaneous radiation injuries: models, assessment and treatments.\" (2020)","DOI":"10.1667\/RADE-20-00120.1"},{"key":"35","doi-asserted-by":"crossref","unstructured":"GM Videtic, KL Stephans, NM Woody, et al.  \"Int J Radiat Oncol Biol Phys.\"  90, \"30 Gy or 34 Gy? 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Neuroinflammation.\"  15, \"Prostaglandin D2\/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets.\" 272 (2018)","DOI":"10.1186\/s12974-018-1305-3"},{"key":"47","doi-asserted-by":"crossref","unstructured":"JA Avila, M Kiprowska, T Jean-Louis, et al.  \"Brain Behav.\"  10, \"PACAP27 mitigates an age-dependent hippocampal vulnerability to PGJ2-induced spatial learning deficits and neuroinflammation in mice.\" e01465 (2020)","DOI":"10.1002\/brb3.1465"},{"key":"48","doi-asserted-by":"crossref","unstructured":"S Zhang, X Wu, S Yu,  \"Dis Esophagus.\"  27, \"Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus.\" (2014)","DOI":"10.1111\/dote.12118"},{"key":"49","doi-asserted-by":"crossref","unstructured":"C O'Connell, D Amar, A Boucly, et al.  \"Drug Saf.\"  39, \"Comparative Safety and Tolerability of Prostacyclins in Pulmonary Hypertension.\" (2016)","DOI":"10.1007\/s40264-015-0365-x"},{"key":"50","doi-asserted-by":"crossref","unstructured":"WL Smith, Y Urade, PJ Jakobsson,  \"Chem Rev.\"  111, \"Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis.\" (2011)","DOI":"10.1021\/cr2002992"},{"key":"52","doi-asserted-by":"crossref","unstructured":"M Hofer, Z Hoferov\u00e1, M Falk,  \"Molecules.\"  24, \"Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome.\" 4019 (2019)","DOI":"10.3390\/molecules24224019"},{"key":"53","doi-asserted-by":"crossref","unstructured":"EC Laiakis, K Strassburg, R Bogumil, et al.  \"J Proteome Res.\"  13, \"Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.\" 4143 (2014)","DOI":"10.1021\/pr5005295"},{"key":"54","doi-asserted-by":"crossref","unstructured":"M Goudarzi, WM Weber, TD Mak, et al.  \"J Proteome Res.\"  14, \"Metabolomic and lipidomic analysis of serum from mice exposed to an internal emitter, cesium-137, using a shotgun LC-MS(E) approach.\" 374 (2015)","DOI":"10.1021\/pr500913n"},{"key":"55","doi-asserted-by":"crossref","unstructured":"LK Steel  and GN Catravas  \"Int J Radiat Biol Relat Stud Phys Chem Med.\"  42, \"Radiation-induced changes in production of prostaglandins F2 alpha, E, and thromboxane B2 in guinea pig parenchymal lung tissues.\" 517 (1982)","DOI":"10.1080\/09553008214551461"},{"key":"56","doi-asserted-by":"crossref","unstructured":"M Donlon, L Steel, EA Helgeson, et al.  \"Life Sci.\"  32, \"Radiation-induced alterations in prostaglandin excretion in the rat.\" 2631 (1983)","DOI":"10.1016\/0024-3205(83)90354-5"},{"key":"51","doi-asserted-by":"crossref","unstructured":"DL Simmons, RM Botting, T Hla,  \"Pharmacol Rev.\"  56, \"Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition.\" 387 (2004)","DOI":"10.1124\/pr.56.3.3"},{"key":"34","doi-asserted-by":"crossref","unstructured":"RA Schlaak, G SenthilKumar, M Boerma, et al.  \"Cancers (Basel).\"  12, \"Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity.\" 415 (2020)","DOI":"10.3390\/cancers12020415"}],"container-title":["Radiation 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