{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:50:44Z","timestamp":1791240644415,"version":"4.1.0"},"reference-count":35,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,11,10]]},"abstract":"<jats:p>This study aims to elucidate the processes involved in radiation-induced liver injury and subsequent hepatocyte proliferation, and to identify novel metabolic profiles associated with progression of liver injury and hepatocyte proliferation. Six-week-old male Sprague-Dawley rats were exposed to a single 25 Gy dose of radiation to the whole liver to induce a model of radiation-induced liver injury and subsequent hepatocyte proliferation. Liver injury and hepatocyte proliferation were assessed using a range of techniques, including Masson's trichrome staining, liver histopathology, ELISA, immunohistochemistry, and Western blotting. Dynamic changes in metabolic profiles and biomarker concentrations in liver tissue were investigated using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry. After radiation exposure, acute radiation-induced liver dysfunction occurs, but then there is gradual recovery over time, concomitant with the onset of hepatocyte proliferation. Metabolomic analysis of liver tissues at different time points, specifically day 1, day 8, day 15, and day 30 postirradiation, revealed notable differences in all 22 metabolites, with a predominance of lipid metabolites. Among them, 9 metabolites showed more than a twofold change on days 15 and 30. We validated the correlation between these 9 metabolites with injury scores and Ki-67 positive cells (%). Notably, there was a strong negative correlation between glycerylphosphorylethanolamine (GPE) and the injury score (correlation coefficient: -0.701) and between 1-hexadecanoyl-2-(5-hydroxy-8-oxo-6E-octenoyl)-sn-glycero-3-phosphoserine (PHOOA-PS) and the Ki-67 positive cells (%) (correlation coefficient: \u20130.824). Additionally, GPE has significant value in differentiating the degree of injury [area under the curve (AUC) = 0.958]. This study successfully established a rat model of radiation-induced hepatic injury and subsequent hepatocyte proliferation, shedding light on dynamic metabolic changes at different times.<\/jats:p>","DOI":"10.1667\/rade-24-00112.1","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T11:26:00Z","timestamp":1762773960000},"page":"100-112","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Metabolomics Atlas of Radiation-induced Liver Injury and Hepatocyte Proliferation Process in Rat"],"prefix":"10.1667","volume":"205","author":[{"given":"Qiaoyuan Wu","family":"M.M.","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing Li","family":"M.M.","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Health Science Center at Houston, University of Texas, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingshi","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"publisher","unstructured":"A Vogel, T Meyer, G Sapisochin, et al.  \"Lancet.\"  400, \"Hepatocellular carcinoma.\" 1345 (2022)","DOI":"10.1016\/s0140-6736(22)01200-4"},{"key":"2","doi-asserted-by":"publisher","unstructured":"TS Su, SX Liang, LQ Li, et al.  \"J Clin Transl Hepatol.\"  11, \"New staging model for radiation-based hepatocellular carcinoma treatment: A national multicenter study.\" 341 (2023)","DOI":"10.14218\/JCTH.2022.00002"},{"key":"3","doi-asserted-by":"publisher","unstructured":"S Apisarnthanarax, A Barry, M Cao, et al.  \"Pract Radiat Oncol.\"  12, \"External beam radiation therapy for primary liver cancers: An ASTRO clinical practice guideline.\" 28 (2022)","DOI":"10.1016\/j.prro.2021.09.004"},{"key":"4","doi-asserted-by":"publisher","unstructured":"SX Liang, XD Zhu, HJ Lu, et al.  \"Cancer.\"  103, \"Hypofractionated three-dimensional conformal radiation therapy for primary liver carcinoma.\" 2181 (2005)","DOI":"10.1002\/cncr.21012"},{"key":"5","doi-asserted-by":"publisher","unstructured":"SX Liang, XB Huang, XD Zhu, et al.  \"Radiother Oncol.\"  98, \"Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis.\" 265 (2011)","DOI":"10.1016\/j.radonc.2010.10.014"},{"key":"6","doi-asserted-by":"publisher","unstructured":"ZY Xu, SX 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Goodman,  \"J Hepatol.\"  47, \"Grading and staging systems for inflammation and fibrosis in chronic liver diseases.\" 598 (2007)","DOI":"10.1016\/j.jhep.2007.07.006"},{"key":"17","doi-asserted-by":"publisher","unstructured":"M Imaeda, H Ishikawa, Y Yoshida, et al.  \"J Radiat Res.\"  55, \"Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.\" 665 (2014)","DOI":"10.1093\/jrr\/rru005"},{"key":"18","doi-asserted-by":"crossref","unstructured":"JP Geraci  and Mariano Ms  \"Radiat Res.\"  136, \"Radiation hepatology of the rat: parenchymal and nonparenchymal cell injury.\" 205 (1993)","DOI":"10.2307\/3578612"},{"key":"19","doi-asserted-by":"publisher","unstructured":"Z-G Ren, J Wang, K Gu, et al.  \"Mol Biol Rep.\"  39, \"Hepatic proliferation after partial liver irradiation in Sprague\u2013Dawley rats.\" 3829 (2012)","DOI":"10.1007\/s11033-011-1161-z"},{"key":"20","doi-asserted-by":"publisher","unstructured":"M Urabe, H Hikita, Y Saito, et al.  \"Hepatol Commun.\"  2, \"Activation of p53 After Irradiation Impairs the Regenerative Capacity of the Mouse Liver.\" 411 (2022)","DOI":"10.1002\/hep4.1815"},{"key":"21","doi-asserted-by":"publisher","unstructured":"GK Michalopoulos  and MC DeFrances  \"Science.\"  276, \"Liver regeneration.\" 60 (1997)","DOI":"10.1126\/science.276.5309.60"},{"key":"22","doi-asserted-by":"publisher","unstructured":"SE Theocharis, AS Skopelitou, AP Margeli, et al.  \"Dig Dis Sci.\"  39, \"Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy.\" 245 (1994)","DOI":"10.1007\/BF02090193"},{"key":"23","doi-asserted-by":"publisher","unstructured":"C Gerlach, DY Sakkab, T Scholzen, et al.  \"Hepatology.\"  26, \"Ki-67 expression during rat liver regeneration after partial hepatectomy.\" 573 (1997)","DOI":"10.1002\/hep.510260307"},{"key":"25","doi-asserted-by":"publisher","unstructured":"DT Chao, JK Lim, WS Ayoub, et al.  \"Aliment Pharmacol Ther.\"  39, \"Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase \u2264 40 IU\/L and significant hepatic fibrosis.\" 349 (2014)","DOI":"10.1111\/apt.12590.STOP"},{"key":"26","doi-asserted-by":"publisher","unstructured":"R Lichtinghagen, D Pietsch, H Bantel, et al.  \"J Hepatol.\"  59, \"The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values.\" 236 (2013)","DOI":"10.1016\/j.jhep.2013.03.016"},{"key":"28","doi-asserted-by":"publisher","unstructured":"LD. 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