Investigating the mechanisms of Triclocarban-induced liver injury: A comprehensive analysisbased on network toxicology and in vivo experiments
Xinyu Fang, Jinfeng Zhao, Simin Wu, Peng Liao, Guiping Guan · Environmental Pollution · 2025
Triclocarban (TCC) is a widely used antibacterial agent with chemical stability and lipophilicity, posing potential health risks due to environmental accumulation and bioaccumulation. This research explored the toxicological features and molecular pathways underlying TCC-induced liver damage through a combination of network toxicology, molecular docking, and in vivo studies. Network toxicology identified 269 potential targets and nine core genes, associated with TCC-induced liver damage. Molecular docking studies indicated significant binding affinities between TCC and the core proteins, implying potential functional interference. In vivo experiments with weaned piglets showed significant liver toxicity at high TCC doses, characterized by decreased liver index, elevated serum ALT and AST, and histopathological damage. High-dose TCC also inhibited antioxidant enzyme activities (GSH-PX and CAT), reduced T-AOC and T-SOD, and increased MDA levels. RT-qPCR analysis further confirmed that the mRNA levels of key target genes-including AKT1, HIF1A, EGFR, ALB, MMP9, BCL2L1, ANXA5, and PTGS2-were significantly up-regulated in the liver, whereas no significant change was observed for the core gene ESR1.This indicates the activation of oxidative stress and inflammatory pathways. These findings provide new insights into TCC-induced hepatotoxicity and highlight the need for further research on intervention targets and comprehensive health risk assessments across different exposures and species.