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网络毒理学和分子对接阐明了山梨酸钾的肝毒性和致癌机制,并通过体外试验得到验证。

Network toxicology and molecular docking elucidate the hepatotoxic and carcinogenic mechanisms of potassium sorbate validated by in vitro assays.

作者信息

Li Yueyue, Dai Weiqi, Li Jingjing, Mo Wenhui, Xu Xuanfu

机构信息

Department of Gastroenterology, Shidong Hospital of Shanghai, Shanghai, 200438, China.

出版信息

Sci Rep. 2025 Aug 25;15(1):31225. doi: 10.1038/s41598-025-17255-z.

DOI:10.1038/s41598-025-17255-z
PMID:40854970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12379242/
Abstract

Potassium sorbate is a preservative widely used in various industrial products, and its potential toxicity and environmental risks are worthy of further exploration. This study provides a novel elucidation of the ecological toxicity mechanism of potassium sorbate, supported by in vitro cell model validation, thereby offering system-level to molecular-level analysis for the risk assessment and management of food additives. A total of 124 and 106 potential targets for hepatotoxicity and carcinogenicity were identified, respectively, and protein-protein interaction networks and Cytoscape were used to determine the hub genes associated with the toxicity of potassium sorbate. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the pathways induced by potassium sorbate were associated with cancer-related chemicals and pathways. Molecular docking results showed that potassium sorbate had high degree of affinity with the hub targets, which, combined with in vitro cell line validation, further supported the mechanism of action of potassium sorbate in the regulation of hepatocyte injury, tumor cell proliferation, and apoptosis. This study provides a novel perspective on the toxicity of potassium sorbate, and offers a theoretical basis for its safety assessment and risk management in clinical applications.

摘要

山梨酸钾是一种广泛应用于各种工业产品中的防腐剂,其潜在毒性和环境风险值得进一步探索。本研究通过体外细胞模型验证,对山梨酸钾的生态毒性机制进行了全新阐释,从而为食品添加剂的风险评估和管理提供了从系统水平到分子水平的分析。分别确定了124个和106个肝毒性和致癌性的潜在靶点,并利用蛋白质-蛋白质相互作用网络和Cytoscape软件确定了与山梨酸钾毒性相关的枢纽基因。基因本体论和京都基因与基因组百科全书通路富集分析表明,山梨酸钾诱导的通路与癌症相关化学物质和通路有关。分子对接结果表明,山梨酸钾与枢纽靶点具有高度亲和力,结合体外细胞系验证,进一步支持了山梨酸钾在调节肝细胞损伤、肿瘤细胞增殖和凋亡中的作用机制。本研究为山梨酸钾的毒性提供了新的视角,并为其临床应用中的安全性评估和风险管理提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/f8c3dc591cef/41598_2025_17255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/a86099227341/41598_2025_17255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/a589290d02ee/41598_2025_17255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/27a8e5d4fd5f/41598_2025_17255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/266e7dec8dd5/41598_2025_17255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/b740157fc369/41598_2025_17255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/f8c3dc591cef/41598_2025_17255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/a86099227341/41598_2025_17255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/a589290d02ee/41598_2025_17255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/27a8e5d4fd5f/41598_2025_17255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/266e7dec8dd5/41598_2025_17255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/b740157fc369/41598_2025_17255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f8/12379242/f8c3dc591cef/41598_2025_17255_Fig6_HTML.jpg

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