Polystyrene Microplastics Exacerbate Arsenic-Induced Ferroptosis and Lipid Metabolism Dysregulation in Chicken Hepatocytes through SIRT7-SIRT1 Axis-Associated Transcriptomic Alterations

Co-contamination with arsenic (As) and polystyrene microplastics (PS-MPs) poses a significant risk to environmental health. This study elucidated the synergistic toxicity mechanism of PS-MPs and As using a chicken hepatocyte model, integrating electron microscopy, migration assays, and comprehensive biomarker assessment. Toxicity prediction, molecular docking, transcriptomics, protein-protein interaction networks, and Pearson correlation analysis were further employed to clarify the underlying mechanism of their combined toxic effects. Molecular docking analysis provided supporting computational evidence that the styrene monomer derived from PS-MPs interferes with antioxidant proteins (e.g., SIRT1), suggesting a possible mechanism by which PS-MPs could exacerbate intracellular As accumulation. This interaction precipitates a vicious cycle of oxidative stress and lipid metabolism disorders. Further research has found that synergistic toxicity was significantly associated with a coordinated dysregulation of SIRT7 and SIRT1, suggesting a perturbation of the dynamic balance between these two regulators. This imbalance subsequently suppresses PPAR-α signaling and GPX4, while upregulating lipid accumulation markers and ferroptosis drivers such as ACSL4. These findings, together with functional validation via SIRT1 overexpression and SIRT7 knockdown, identify a potential core regulatory axis of the SIRT7-SIRT1 protein network in the synergistic toxicity of As-PS-MPs. Our research provides a new framework for the toxicological analysis of PS-MPs and As through transcriptomics and bioinformatics analysis and offers new ideas for further studies on combined pollutant exposure.