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

Abstract

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 hepatotoxicity by inducing hepatic oxidative stress and aberrant activation of multiple signaling pathways. The findings offer novel data for the comprehensive toxicological assessment of TCS, contribute to safeguarding animal and human health, and propose a framework for the integrated risk assessment of similar environmental contaminants.

The authors' abstract, as published at the source. Chemical Research in Toxicology, 2025 · DOI ↗