Emerging contaminant fluorinated liquid crystal monomer 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB)-induced hepatotoxicity: Insights from combined transcriptomics and metabolomics approaches.

Fluorinated liquid crystal monomers (FLCMs) are widely used in liquid crystal display (LCD) panels. However, as emerging contaminants, FLCMs have been detected in various environments and proven to be toxic to humans. This study aimed to investigate the molecular mechanisms underlying the hepatotoxicity of a typical FLCM, 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), in HepG2 cells. EDPrB exposure (25 mg/L) induced oxidative stress, evidenced by reduced CAT activity (1.87-fold) and increased MDA content (2.12-fold) (p < 0.05). 25 mg/L EDPrB disrupted the metabolism, significantly elevating the levels of TC (1.65-fold, p < 0.001), TG (1.47-fold, p < 0.01), and GLU (1.44-fold, p < 0.05), respectively. Comprehensive analysis of transcriptomics and metabolomics revealed that EDPrB affected lipid and glucose metabolisms, antioxidant defense-related pathways, and PI3K/AKT/mTOR signaling pathways. Additionally, the altered expression of metabolism-related genes confirmed the promotion of fatty acid synthesis and glycolysis. The altered expression of PI3K, AKT, and mTOR proteins, coupled with their strong binding affinity to EDPrB, collectively revealed the dysregulation of PI3K/AKT/mTOR pathways. Protein-protein interaction (PPI) analysis further verified the interaction between lipid and glucose metabolism disorders, oxidative stress, and PI3K/AKT/mTOR pathways dysfunction, contributing to EDPrB-induced hepatotoxicity. Our findings provide valuable insights into the potential health risks of FLCMs.