{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:47:29Z","timestamp":1787168849758,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Research Institute Public Project","award":["GY2024Z-1, GY2024D-1"],"award-info":[{"award-number":["GY2024Z-1, GY2024D-1"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3302002"],"award-info":[{"award-number":["2022YFC3302002"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Key Laboratory of Forensic Medicine","award":["21DZ2270800"],"award-info":[{"award-number":["21DZ2270800"]}]},{"name":"PhD Research Startup Foundation of Nantong University","award":["25B11"],"award-info":[{"award-number":["25B11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>As a typical halogenated hydrocarbon environmental pollutant, 1,2-dichloroethane (1,2-DCE) exhibits clinically confirmed hepatotoxicity with incompletely understood mechanisms. This study integrated network toxicology, molecular docking, and in vitro experiments to investigate necroptosis in 1,2-DCE-induced liver injury. Computational analysis predicted involvement of the aryl hydrocarbon receptor (AHR)\/cytochrome P450 1A1 (CYP1A1) pathway, and molecular docking suggested potential binding between 1,2-DCE and AHR (\u22126.5 kcal\/mol). CCK-8 assays showed that 1,2-DCE reduced THLE-2 hepatocyte viability in a concentration-dependent manner. Notably, 1,2-DCE triggered rapid AHR nuclear translocation within 1 h and transiently upregulated CYP1A1 at both the transcriptional and protein levels (3\u20136 h). Further studies revealed elevated intracellular reactive oxygen species (ROS) at 24 h. After 48 h exposure, CYP1A1 expression was significantly suppressed, accompanied by activation of necroptosis markers, including increased lactate dehydrogenase (LDH) release, enhanced propidium iodide (PI) staining, and elevated phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). These findings reveal a dual-phase mechanism: an early adaptive stress response via the AHR-CYP1A1 axis, followed by pathway dysfunction and transition to necroptosis, suggesting AHR as a potential target for intervening in 1,2-DCE-induced hepatotoxicity.<\/jats:p>","DOI":"10.3390\/toxics14020136","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:22Z","timestamp":1769771362000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AHR-CYP1A1 Axis Perturbation and Necroptosis in 1,2-Dichloroethane Hepatotoxicity: Elucidation by an Integrated Network Toxicology and In Vitro Validation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-7378","authenticated-orcid":false,"given":"Yichang","family":"Liu","sequence":"first","affiliation":[{"name":"College of Medicine, Nantong University, Nantong 226000, China"},{"name":"Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Medicine, Nantong University, Nantong 226000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Tian","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hewen","family":"Dong","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Ma","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Meng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, 1838 Guangzhoudadaobei, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2025-3254","authenticated-orcid":false,"given":"Ningguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai Forensic Service Platform, Academy of Forensic Science, Shanghai 200063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","first-page":"350","article-title":"Aliphatic Halogenated Hydrocarbons: Report and Analysis of Liver Injury in 60 Patients","volume":"6","author":"Teschke","year":"2018","journal-title":"J. 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