{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T21:51:16Z","timestamp":1769637076935,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hebei Province International Science and Technology Cooperation Project","award":["24292401Z"],"award-info":[{"award-number":["24292401Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Drug-induced liver injury (DILI), a major type of adverse drug reaction, has become one of the leading causes of acute liver injury and liver failure worldwide. Its clinical significance lies not only in acute hepatocyte necrosis and functional failure but also in its role as a key initiating factor for liver cancer progression. Therefore, early diagnosis of DILI is of great importance. Methods: This study employed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS\/MS) to perform widely targeted metabolomics analysis on acetaminophen (APAP)-induced liver injury mice and healthy mice. Results: UPLC-QTRAP-MS\/MS identified 41 differentially expressed metabolites primarily involved in glycerophospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and glutathione metabolism pathways. The significant elevation of serum and hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) confirmed the successful establishment of the drug-induced liver injury (DILI) model. ROC curve analysis indicated 11 metabolites with AUC values exceeding 0.90 as potential biomarkers, including (R)-2-Hydroxybutyric acid, Glu-Gln, \u03b3-Glu-Gln, 2-Methyllactic acid, L-Serine, Hyodeoxycholic acid, 3-Epideoxycholic acid, and Glycochenodeoxycholic acid 7-sulfate. Conclusions: We propose that these differential metabolites may serve as candidate biomarkers for DILI. Our findings provide a novel metabolomic signature derived directly from the injured tissue and offer a theoretical foundation for further research into early diagnosis of drug-induced liver injury.<\/jats:p>","DOI":"10.3390\/metabo16020096","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:48:04Z","timestamp":1769590084000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Widely Targeted Liver Metabolomics Reveals Potential Biomarkers in Mice with Drug-Induced Liver Injury"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7582-8121","authenticated-orcid":false,"given":"Jiangning","family":"Peng","sequence":"first","affiliation":[{"name":"College of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hebei Institute of Drug and Medical Device Inspection, Shijiazhuang 050027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuehong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University, Kaifeng 475004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"McCombs Institute for the Early Detection and Treatment of Cancer, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Institute of Drug and Medical Device Inspection, Shijiazhuang 050027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Hengshui Comprehensive Inspection and Testing Center, Hengshui 053000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.23736\/S2724-5985.20.02795-6","article-title":"Drug induced liver injury: From pathogenesis to liver transplantation","volume":"67","author":"Germani","year":"2021","journal-title":"Minerva Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/liv.15262","article-title":"Incidence and risk factors of drug-induced liver injury","volume":"42","author":"Li","year":"2022","journal-title":"Liver Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13020-021-00543-x","article-title":"Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs","volume":"16","author":"Zhou","year":"2021","journal-title":"Chin. 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