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毒死蜱在每日允许摄入量下抑制肠道干细胞增殖和分化,并在高剂量时破坏免疫反应。

Chlorpyrifos Inhibits Intestinal Stem Cell Proliferation and Differentiation at the Acceptable Daily Intake and Disrupts Immune Responses at High Doses.

作者信息

Yuan Xinlei, Wu Fang, Cheng Le, Ji Tengteng, Zheng Chenyan, Ma Yumeng, Jin Yutong, Dong Jianguo, Jin Yan, Fang Bing

机构信息

Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.

State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China.

出版信息

J Agric Food Chem. 2025 May 21;73(20):12455-12464. doi: 10.1021/acs.jafc.4c13249. Epub 2025 May 13.

DOI:10.1021/acs.jafc.4c13249
PMID:40357541
Abstract

The acceptable daily intake (ADI) and maximum residue limits in food for chlorpyrifos (CPF), a widely used organophosphorus pesticide, may damage the intestine. Here, we evaluated damage to the intestine by CPF at the ADI (0.01 mg/kg bodyweight/day) and at 10 times the ADI (10ADI; 0.1 mg/kg bodyweight/day) in mice after 8 weeks of exposure and evaluated the resulting immune response to an enterotoxigenic (ETEC) infection. CPF at the ADI dose significantly disrupted the intestinal integrity and intestinal stem cell functionality, which may be associated with reduced indole-3-propionic acid levels. However, mice in the 10ADI group exhibited only elevated pro-inflammatory cell and cytokine levels. During ETEC infection, intestinal mucosal immunity was activated by the 10ADI dose, as indicated by increased regulatory T cells and IL-10 levels, which were associated with decreased fecal butyric acid content. Our study demonstrated that the effects of pesticide residues appear to be dose-specific, bringing attention to the health risk at the ADI level.

摘要

毒死蜱(CPF)是一种广泛使用的有机磷农药,其每日允许摄入量(ADI)和食品中的最大残留限量可能会损害肠道。在此,我们评估了小鼠在暴露8周后,毒死蜱以ADI(0.01毫克/千克体重/天)和10倍ADI(10ADI;0.1毫克/千克体重/天)剂量对肠道的损害,并评估了由此产生的对产肠毒素大肠杆菌(ETEC)感染的免疫反应。ADI剂量的毒死蜱显著破坏了肠道完整性和肠道干细胞功能,这可能与吲哚-3-丙酸水平降低有关。然而,10ADI组的小鼠仅表现出促炎细胞和细胞因子水平升高。在ETEC感染期间,10ADI剂量激活了肠道黏膜免疫,表现为调节性T细胞和白细胞介素-10水平升高,这与粪便丁酸含量降低有关。我们的研究表明,农药残留的影响似乎具有剂量特异性,这引起了人们对ADI水平健康风险的关注。

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