Multi-omics integration reveals underlying toxicological mechanisms of triclosan in the freshwater fish model Zacco platypus.

Although the partial mechanisms of triclosan toxicity have been suggested in fish models, integrated omics approaches for understanding its overall effects are still lacking in non-model fish species. In this study, we utilized a multi-omics platform that integrates the transcriptome, proteome, and metabolome to understand the underlying molecular toxicological mechanisms of triclosan (TCS) in the pale chub, Zacco platypus. Z. platypus was exposed to three concentrations of TCS (1, 50, and 200 μg L), including an environmentally relevant dose, for 96 h. Molecular and biochemical responses were then analyzed in liver tissues at the transcriptomic, proteomic, and metabolomic levels, after integration with in silico bioinformatics. Our findings revealed that the primary toxic mechanism of TCS involved the accumulation of misfolded proteins in the endoplasmic reticulum (ER), leading to increased ER stress. This was accompanied by a significant downregulation of carbohydrate and amino acid metabolism, which inhibited energy metabolism. These pathways were associated with pronounced oxidative stress, as confirmed by increased reactive oxygen species (ROS) levels and reduced glutathione (GSH) contents. Taken together, by integrating multi-omics datasets, we identified key toxicological pathways underlying TCS exposure to fish.