Abstract：
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.
摘要：
食品安全与人类健康息息相关。噻菌灵被广泛用作蔬菜和水果等农产品的杀真菌剂和除臭剂，以防止运输和储存期间的真菌感染。本研究旨在使用新型网络毒理学和分子对接技术研究噻菌灵的毒性和潜在机制。首先,ADMETLab2.0和ADMETsar数据库，随着文学,预测噻菌灵诱导癌症和肝损伤的潜力。使用GeneCards和TCMIP数据库构建疾病靶文库，而噻菌灵靶文库是使用瑞士靶预测和TCMIP数据库构建的。维恩数据库确定了与噻菌灵诱导的癌症和肝损伤相关的潜在靶标。蛋白质-蛋白质相互作用(PPI)网络来自STRING数据库，从DAVID数据库获得基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径。分子对接评估噻菌灵与核心靶标之间的结合亲和力。该研究揭示了噻菌灵诱导的癌症的29个潜在靶标和肝损伤的30个潜在靶标。PPI确定了噻菌灵诱导的癌症的5个核心靶标和诱导肝损伤的4个核心靶标。KEGG分析表明，噻菌灵可能通过细胞周期蛋白依赖性激酶2（CDK2）和表皮生长因子受体（EGFR）靶标诱导胃癌和前列腺癌。和肝损伤通过相同的目标，以p53信号通路为中心。GO分析表明，噻菌灵诱导的癌症和肝损伤与有丝分裂细胞周期G2/M转换和DNA复制有关。分子对接显示噻菌灵与CDK1、CDK2、EGFR、和检查点激酶1（CHEK1）。这些发现表明噻菌灵可能通过p53信号通路影响有丝分裂细胞周期的G2/M转换。可能诱发癌症和肝损伤。本研究为理解噻菌灵毒性的潜在分子机制提供了理论基础。帮助预防和治疗相关疾病。此外,网络毒理学方法加速了未表征的农业化学品的毒性途径的阐明。
