Unraveling the hepatic and immune toxicity of triclosan: an integrative network toxicology, molecular docking, and experimental study

Triclosan exhibits broad-spectrum antibacterial and antifungal activities, but its application in personal care products has been restricted due to potential toxicity and environmental risks. Systematic evaluation of triclosan’s toxicity and underlying mechanisms is urgently needed. This is an integrative preclinical study. We combined computational prediction, cell experiments and animal tests. Computational analyses screened possible toxic targets of triclosan. We further verified these results using in vitro hepatocyte models and in vivo mouse liver injury models. During the investigation of the effects of triclosan on the liver of mice, we identified 27 target points related to liver injury and 19 target points related to immune injury. There was a significant overlap between these two sets of targets. And network analysis confirmed four key hub genes, namely COMT, HSP90AA1, GSTP1, and TTR. Molecular docking results demonstrated stable binding affinity between triclosan and these core targets, and the changes in gene and protein expression levels were further validated in both in vivo and in vitro models. We found the significant overlap between triclosan-induced liver injury and immune injury targets, revealing an inherent association between these two types of toxicity. This study provides a theoretical basis for comprehensively understanding the molecular mechanisms underlying triclosan-induced liver and immune injury. It also offers valuable guidance for developing strategies to mitigate triclosan’s toxicity to humans and the environment. Not applicable.