Assessing the toxicological effects and mechanism of plasticizer exposure on inflammatory bowel disease based on network toxicology and molecular docking

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-05-10 DOI:10.1016/j.fct.2025.115543

Ning Tang , Wentao Sun , Jingke Zhang , Xin Ma , Yan Wang

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引用次数: 0

Abstract

Phthalates (PAEs) are one of the most commonly used plasticizers. Due to their good performance, they are widely used in daily production, such as food packaging, paints, adhesives, children's toys, lubricants and building materials. However, PAEs usually have weak interactions with polymers, which can easily cause environmental pollution in use. These plasticizers have been linked to various health conditions, including inflammatory disorders. They are less intensively studied in the occurrence of inflammation, especially inflammatory bowel disease (IBD), and the necessity to evaluate their pathogenic molecular toxicity is particularly urgent. In this study, network toxicology and molecular docking methods were used to study the toxicological mechanism of IBD induced by four common plasticizers (DBP, DEHP, DEP, DNOP). Potential related targets were predicted using the PharmMapper, SwissStargetPrediction, GeneCards, DisGeNET, OMIM and TTD databases, and 286 related targets were identified. Using Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, binding protein-Protein Interaction (PPI) networks and cytoHubba plug-ins, ten relevant signaling pathways (PI3K-Akt signaling pathway, lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, Proteoglycans in cancer, and so on.) and ten hub genes were identified. Four plasticizers (DBP, DEHP, DEP, DNOP) and the top 10 selected Hub gene targets (SRC, KRAS, PIK3CA, PIK3R1, JAK2, PTPN11, PIK3CD, HRAS, PIK3CG, EGFR) were analyzed by molecular docking. This study provides valuable insights into the molecular mechanisms of plasticizer-induced IBD and highlights the practicality of network toxicology in assessing the toxicity of emerging environmental pollutants. It enhances our understanding of the health risks posed by plasticizers and offers new strategies for mitigating their impact on inflammatory diseases.

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基于网络毒理学和分子对接的增塑剂暴露对炎症性肠病的毒理学效应及机制评估

邻苯二甲酸酯（PAEs）是最常用的增塑剂之一。由于其良好的性能，被广泛应用于日常生产中，如食品包装、油漆、粘合剂、儿童玩具、润滑剂和建筑材料等。然而，PAEs通常与聚合物的相互作用较弱，在使用中容易造成环境污染。这些增塑剂与各种健康状况有关，包括炎症性疾病。它们在炎症，特别是炎症性肠病（IBD）发生中的研究较少，评估其致病分子毒性的必要性尤为迫切。本研究采用网络毒理学和分子对接方法，研究了四种常用增塑剂（DBP、DEHP、DEP、DNOP）诱导IBD的毒理学机制。利用PharmMapper、SwissStargetPrediction、GeneCards、DisGeNET、OMIM和TTD数据库预测潜在的相关靶点，共鉴定出286个相关靶点。利用基因本体（GO）功能注释和京都基因与基因组百科（KEGG）途径富集、结合蛋白-蛋白相互作用（PPI）网络和cytoHubba插件，鉴定了10个相关信号通路（PI3K-Akt信号通路、脂质和动脉粥样硬化、糖尿病并发症AGE-RAGE信号通路、癌症中的蛋白聚糖等）和10个枢纽基因。通过分子对接分析4种增塑剂（DBP、DEHP、DEP、DNOP）和前10个选定的Hub基因靶点（SRC、KRAS、PIK3CA、PIK3R1、JAK2、PTPN11、PIK3CD、HRAS、PIK3CG、EGFR）。这项研究为增塑剂诱导IBD的分子机制提供了有价值的见解，并强调了网络毒理学在评估新出现的环境污染物毒性方面的实用性。它增强了我们对增塑剂带来的健康风险的理解，并提供了减轻增塑剂对炎症性疾病影响的新策略。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.