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丙烯醛清除剂和解毒剂:从黄酮类化合物的高通量筛选到没食子儿茶素没食子酸酯的作用机制研究。

Acrolein scavengers and detoxification: From high-throughput screening of flavonoids to mechanistic study of epigallocatechin gallate.

机构信息

Department of Food Science and Engineering, Jinan University, Guangzhou 510632, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National, Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China; Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering and Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China.

Department of Hematology, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou 510317, China.

出版信息

J Hazard Mater. 2024 Dec 5;480:135873. doi: 10.1016/j.jhazmat.2024.135873. Epub 2024 Sep 17.

DOI:10.1016/j.jhazmat.2024.135873
PMID:39305594
Abstract

Acrolein (ACR) is a widespread, highly toxic substance that poses significant health risks. Flavonoids have been recognized as effective ACR scavengers, offering a possible way to reduce these risks. However, the lack of specific high-throughput screening methods has limited the identification of ACR scavengers, and their actual detoxifying capacity on ACR remains unknown. To address this, we developed a high-throughput screening platform to assess the ACR scavenging capacity of 322 flavonoids. Our results showed that 80.7 % of the flavonoids could scavenge ACR, but only 34.4 % exhibited detoxifying effects in an ACR-injured QSG7701 cell model. Some flavonoids even increased toxicity. Structure-activity relationship (SAR) analysis indicated that galloyl and pyrogallol units enhance scavenging but worsen ACR-induced cytotoxicity. Further investigation revealed that epigallocatechin gallate (EGCG) could exacerbate ACR-induced redox disorder, leading to cell apoptosis. Our findings provide crucial data on the scavenging and detoxifying capacities of 322 flavonoids, highlighting that ACR scavengers might not mitigate ACR-induced toxicity and could pose additional safety risks.

摘要

丙烯醛(ACR)是一种广泛存在且毒性很强的物质,对健康构成重大威胁。类黄酮已被认为是有效的 ACR 清除剂,为降低这些风险提供了一种可能的途径。然而,缺乏特定的高通量筛选方法限制了 ACR 清除剂的鉴定,其对 ACR 的实际解毒能力仍不清楚。为了解决这个问题,我们开发了一个高通量筛选平台来评估 322 种类黄酮对 ACR 的清除能力。我们的结果表明,80.7%的类黄酮可以清除 ACR,但只有 34.4%在 ACR 损伤的 QSG7701 细胞模型中表现出解毒作用。一些类黄酮甚至增加了毒性。构效关系(SAR)分析表明,没食子酰基和焦没食子酰基单元增强了清除作用,但加重了 ACR 诱导的细胞毒性。进一步的研究表明,表没食子儿茶素没食子酸酯(EGCG)可加重 ACR 诱导的氧化还原紊乱,导致细胞凋亡。我们的研究结果提供了 322 种类黄酮的清除和解毒能力的关键数据,突出表明 ACR 清除剂可能不会减轻 ACR 诱导的毒性,并且可能带来额外的安全风险。

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