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在斑马鱼模型中使用基于注意力的卷积神经网络和机器学习评估喹啉黄的胚胎毒性作用

Assessment of embryotoxic effects of quinoline yellow using attention-based convolutional neural network and machine learning in zebrafish model.

作者信息

Majdan Magdalena, Maciąg Piotr S, Rogalska Agata

机构信息

Department of Toxicology and Food Science, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.

Warsaw University of Technology, Faculty of Electronics and Information Technology, Institute of Computer Science, Warsaw, Poland.

出版信息

Front Pharmacol. 2025 Aug 1;16:1606214. doi: 10.3389/fphar.2025.1606214. eCollection 2025.

Abstract

Our daily diet often includes food additives found in numerous processed foods. Growing concerns about the toxicity and potential health risks of synthetic dyes have drawn increased attention from researchers and regulatory authorities. This study examines the embryotoxic effects of Quinoline Yellow (QY), a synthetic dye commonly used as an additive, using both and models. Computational studies on QY were conducted using QSAR (Quantitative Structure Activity Relations) analysis to identify the major toxicological endpoints. predictions indicated clastogenic and reproductive toxicities, interaction with androgen and estrogen receptors, and an elevated propensity for skin and respiratory allergies. (zebrafish) embryos were exposed to various concentrations of QY (0.005-2 mg⋅mL) over 48, 72 and 96-h periods. Lethal effects were observed at concentrations above 0.5 mg mL, with a median lethal concentration LC50 of 0.64 mg mL. Exposure to QY (0.5-2 mg⋅mL) resulted in pericardial edema, swollen and necrosed yolk sac, blood stasis and reduced eye size. The study provides direct evidence for the developmental toxicity and teratogenic potential of QY. To enhance the analysis, attention-based Convolutional Neural Networks (CNN) and Transfer Learning (TL) were employed to discern morphological alterations in zebrafish embryos exposed and not exposed to QY. Automating the analysis and classification of zebrafish embryo images diminishes the workload and time burden on biological experts while simultaneously enhancing the reproducibility and objectivity of the classification. The developed neural network further corroborates the evidence suggesting QY's potential toxicity.

摘要

我们的日常饮食通常包含许多加工食品中含有的食品添加剂。人们对合成染料的毒性和潜在健康风险日益担忧,这引起了研究人员和监管机构越来越多的关注。本研究使用[具体模型1]和[具体模型2]模型,研究了喹啉黄(QY)这种常用作添加剂的合成染料的胚胎毒性。利用定量构效关系(QSAR)分析对QY进行了计算研究,以确定主要的毒理学终点。预测表明存在致突变性和生殖毒性、与雄激素和雌激素受体的相互作用,以及皮肤和呼吸道过敏倾向增加。将斑马鱼胚胎在48、72和96小时内暴露于不同浓度的QY(0.005 - 2 mg·mL)中。在浓度高于0.5 mg/mL时观察到致死效应,半数致死浓度LC50为0.64 mg/mL。暴露于QY(0.5 - 2 mg·mL)导致心包水肿、卵黄囊肿胀和坏死、血液淤积以及眼睛尺寸减小。该研究为QY的发育毒性和致畸潜力提供了直接证据。为了加强分析,采用了基于注意力的卷积神经网络(CNN)和迁移学习(TL)来识别暴露和未暴露于QY的斑马鱼胚胎中的形态变化。自动化斑马鱼胚胎图像的分析和分类减少了生物专家的工作量和时间负担,同时提高了分类的可重复性和客观性。所开发的神经网络进一步证实了表明QY潜在毒性的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b31/12354635/f90cef9205b9/fphar-16-1606214-g001.jpg

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