Food safety analysis: network toxicology, molecular docking, machine learning and single-cell analysis to interpret sodium benzoate-induced renal injury from multiple perspectives.

IF 2.7 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-09-09 DOI:10.1080/15376516.2025.2553859

Jingwei Li, Hailong Yang, Jingjia Yang, Jintao Liang, Yalun Liang, Yimao Wu, Runfeng Zhang

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引用次数: 0

Abstract

Background: Sodium benzoate, a common food additive, has raised safety concerns despite its general recognition as safe. This study aimed to investigate the mechanisms of sodium benzoate-induced nephrotoxicity.

Method: A network toxicology approach was used to identify key targets and core pathways involved in sodium benzoate nephrotoxicity. Molecular docking validated the binding affinity between these targets and sodium benzoate. Machine learning and single-cell analysis further explored the underlying mechanisms using dataset validation.

Result: Protein-protein interaction (PPI) network analysis revealed five key targets with the lowest binding energies (Matrix metalloproteinase 2 (MMP2), Estrogen Receptor 1 (ESR1), Poly (ADP-ribose) polymerase 1 (PARP1), Prostaglandin-endoperoxide synthase 2 (PTGS2), Mitogen-activated protein kinase 14 (MAPK14)) as central to sodium benzoate-induced renal injury. Enrichment analysis indicated 'diabetic nephropathy' (DN) as the primary pathway. Machine learning and single-cell analysis confirmed PTGS2 as the dominant factor exerting nephrotoxicity among the key genes.

Conclusion: This multi-method study uncovered potential mechanisms of sodium benzoate-induced renal injury, providing a basis for improving food safety evaluations.

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食品安全分析：网络毒理学、分子对接、机器学习、单细胞分析，多角度解读苯甲酸钠致肾损伤。

背景：苯甲酸钠是一种常见的食品添加剂，尽管人们普遍认为苯甲酸钠是安全的，但它的安全性引起了人们的关注。本研究旨在探讨苯甲酸钠引起肾毒性的机制。方法：采用网络毒理学方法，确定与苯甲酸钠肾毒性相关的关键靶点和核心途径。分子对接验证了这些靶点与苯甲酸钠的结合亲和力。机器学习和单细胞分析使用数据集验证进一步探索了潜在的机制。结果：蛋白-蛋白相互作用（PPI）网络分析揭示了5个结合能最低的关键靶点（基质金属蛋白酶2 （MMP2）、雌激素受体1 （ESR1）、聚（adp -核糖）聚合酶1 （PARP1）、前列腺素内过氧化物合成酶2 （PTGS2）、丝裂原活化蛋白激酶14 (MAPK14)）是苯甲酸钠诱导肾损伤的核心。富集分析表明“糖尿病肾病”（DN）是主要途径。机器学习和单细胞分析证实PTGS2是关键基因中发挥肾毒性的主要因素。结论：本研究揭示了苯甲酸钠致肾损伤的潜在机制，为改进食品安全评价提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.