{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:17Z","timestamp":1760060717989,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["24KJD230003","23KJB180028","2023M732990"],"award-info":[{"award-number":["24KJD230003","23KJB180028","2023M732990"]}]},{"name":"China Postdoctoral Foundation","award":["24KJD230003","23KJB180028","2023M732990"],"award-info":[{"award-number":["24KJD230003","23KJB180028","2023M732990"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Deoxynivalenol (DON), a prevalent environmental toxin produced by Fusarium fungi, frequently contaminates feed and food products. However, the critical metabolites and regulatory factors involved in DON toxicity remain poorly understood. Building upon our established DON-induced porcine intestinal epithelial cells (IPEC-J2) injury model, this study employed liquid chromatography-tandem mass spectrometry (LC-MS\/MS) to conduct metabolomic analysis, and integrated analysis with transcriptomic data from DON-exposed IPEC-J2. Results identified 1524 differentially expressed metabolites, and revealed significant enrichment in Glutathione metabolism and Mucin-type O-glycan biosyn-thesis pathways. Notably, \u03b3-glutamylcysteine (\u03b3GC), the rate-limiting precursor for glutathione synthesis, showed significant reduction following DON exposure. To explore the biological function of \u03b3GC, this study found through exogenous supplementation experiments that \u03b3GC pretreatment could significantly alleviate the inhibition of IPEC-J2 cell viability, effectively reduce intracellular ROS accumulation and inhibit DON-induced apoptosis in IPEC-J2 cells. These results indicated that the severe oxidative stress induced by DON is closely related to the blockage of glutathione synthesis caused by the exhaustion of intracellular \u03b3GC, and revealed the application potential of \u03b3GC as an exogenous supplement in the prevention and treatment of DON exposure. In conclusion, this study offers valuable insights into the metabolic and transcriptional alterations, along with the key metabolites and regulators involved in the cellular response to DON pollution. It also lays a theoretical foundation for more effective prevention and treatment strategies against DON pollution.<\/jats:p>","DOI":"10.3390\/toxins17090457","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:07:15Z","timestamp":1757668035000},"page":"457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Analysis of Metabolome and Transcriptome Identifies the Role of \u03b3-Glutamylcysteine in Mitigating Deoxynivalenol-Induced Toxicity"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaocheng","family":"Bao","sequence":"first","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-3027","authenticated-orcid":false,"given":"Ming-An","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-4647","authenticated-orcid":false,"given":"Hairui","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alshannaq, A., and Yu, J.-H. 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