Efficient analysis of the toxicity and mechanisms of Hexaconazole and two other triazole fungicides: insights from integrated network toxicology, molecular docking and bioinformatics data

Background: The safety of food grains is crucial for human health. Hexaconazole, Propiconazole, and Prothioconazole are widely used triazole fungicides primarily employed in agriculture for the control of plant diseases, aiming to enhance crop yield and quality. Objective: This research aims to elucidate the potential toxic targets and underlying molecular mechanisms of brain and liver damage induced by exposure to the three fungicides through network toxicology combined with molecular docking and bioinformatics data analysis. Method and results: Toxicity analysis through the ADMETlab database showed that the toxicity of the three fungicides was mainly associated with neurotoxicity and liver injury. Systematically utilizing GeneCards, OMIM and other databases and through Cytoscape tools, we identified potential and core targets (including EGFR , CASP3 , ESR1 , PPARG , TP53 , HSP90AA1 , and PTGS2 ) associated with fungicides and brain injury or liver injury. GO and KEGG enrichment analyses indicate that these targets are associated with pathways related to cancer, the PI3K-Akt signaling pathway, organic cyclic compounds, and organic nitrogen compounds. Molecular docking simulations conducted using AutoDock confirmed the high-affinity binding interactions between the fungicides and key target proteins. Conclusions: This study provides a theoretical foundation for understanding the molecular mechanisms underlying the neurotoxicity and hepatotoxicity induced by Hexaconazole, Propiconazole, and Prothioconazole, while establishing a foundational framework for the development of prevention and treatment strategies related to triazole pesticide-associated brain and liver injuries. Our findings underscore the potential risks these three pesticides pose to brain and liver health, highlighting the need for further epidemiological and clinical research in the future.