From Toxicity Assessment to In Vivo Validation: Exploring the Molecular Mechanisms of Triclosan-Induced Liver Injury

作者：Simin Wu, Jinfeng Zhao, Xinyu Fang, Peng Liao, G H Liu · 发表于：Chemical Research in Toxicology · 年份：2025 · DOI：10.1021/acs.chemrestox.5c00380 · 被引用次数：22 · 研究领域：Effects and risks of endocrine disrupting chemicals、Pharmaceutical and Antibiotic Environmental Impacts、Antimicrobial agents and applications

Triclosan (TCS), a synthetic compound initially marketed as a broad-spectrum antibacterial agent, poses significant threats to the environment, animal, and human health due to its inherent toxicity and improper discharge. This study first comprehensively assessed the environmental and biological toxicity of TCS. Subsequently, an integrated approach combining network toxicology, molecular docking, and in vivo experiments was employed to analyze and experimentally validate. For the first time, the mechanisms underlying TCS-induced liver injury in weaned piglets. Results identified 31 major targets associated with TCS-induced liver injury. Molecular docking confirmed strong binding affinity between TCS and the top 10 MCC-ranked core targets. Factor-gene and miRNA-gene regulatory networks were constructed for these core targets. Further GO and KEGG analyses revealed significant enrichment of TCS hepatotoxicity targets in biological processes, including redox regulation, and multiple signaling pathways. Validation via in vivo experiments in weaned piglets demonstrated that TCS exposure significantly induced liver damage and histopathological alterations. It disrupted hepatic redox homeostasis, evidenced by significantly decreased T-AOC, SOD, CAT, and GSH levels, alongside increased MDA levels. Furthermore, TCS significantly upregulated the expression of the Rap1-PI3K/AKT, HIF-1/VEGF, and Ras-MAPK signaling pathways. This study provides the first evidence that TCS exerts hepatotoxi...