Network toxicological and molecular docking to investigate the mechanisms of toxicity of agricultural chemical Thiabendazole.

Autor: He J; Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Minzu University, Nanning, 530006, China; Department of Pharmacology, Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Naning, 530022, China. Electronic address: hejunhui202109@163.com., Zhu X; School of Material Science and Engineering, Hubei University of Automotive Technology, Shiyan, 442000, China., Xu K; Yunnan Provincial Key Laboratory of Wood Adhesives and Glued Products, International Joint Research Center for Biomass Materials, Southwest Forestry University, Kunming, 650224, China., Li Y; Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN, USA., Zhou J; Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Minzu University, Nanning, 530006, China. Electronic address: zhoujuying@126.com.
Jazyk: angličtina
Zdroj: Chemosphere [Chemosphere] 2024 Sep; Vol. 363, pp. 142711. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1016/j.chemosphere.2024.142711
Abstrakt: Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole's potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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