AHR-CYP1A1 Axis Perturbation and Necroptosis in 1,2-Dichloroethane Hepatotoxicity: Elucidation by an Integrated Network Toxicology and In Vitro Validation.

ABSTRACT: 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 (-6.5 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 (3-6 h

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12945068 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature