Lambda-cyhalothrin exposure enhances the development of atherosclerosis in ApoE−/− mice

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-10-01 DOI:10.1016/j.ecoenv.2025.119165

Lei Yu , Haiyan Chen , Lingcheng Li , Haofeng Zhang , Fudong He , Zhenger Fang , Guangjun Zheng , Biying Zhou , Xia Chen , Mingliang Liu , Xiaohua Liang , Guolong Qi , Zhoubin Zhang , Guang Hao

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Abstract

Background

Lambda-cyhalothrin (LCT), a widely used pyrethroid insecticide, has been implicated in the development of metabolic disorders. However, its specific role in atherosclerosis (AS) remains unclear.

Objectives

This study aimed to investigate the influence of LCT on AS development in ApoE^−/−mice and to explore the potential role of metabolomic alterations.

Methods

Eight-week-old male ApoE^−/− mice were fed a high-fat diet for 12 weeks to establish an AS model. Fifteen AS model mice were randomly allocated into three groups (n = 5 per group) for a 15-day intervention: (1) a normal control group (NC), (2) a 45 % high-fat diet (HFD), and (3) an HFD with lambda-cyhalothrin exposure group (HFD+LCT, 1 mg/kg/day). After the intervention, fecal, serum, and aortic samples were collected. Atherosclerotic lesions were evaluated using Oil Red O staining of aortic tissues, and serum lipid profiles were measured. Fecal metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS). Additionally, bioinformatics analysis of two independent gene expression datasets (GSE122165 and GSE124081) was conducted to elucidate the molecular pathways associated with pyrethroid exposure.

Results

Compared with the NC and HFD groups, the HFD+LCT group exhibited significantly increased aortic plaque formation and elevated serum triglyceride (TG) levels. Untargeted metabolomic analysis revealed substantial perturbations in the HFD+LCT group compared to the HFD group, with 159 significantly altered metabolites (108 increased and 51 decreased). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified nine pathways potentially involved in LCT-aggravated AS, including lipid and AS, cholesterol metabolism, and glycerolipid metabolism. The triglyceride species TG (16:0/16:1/16:1) was identified as a potential mediator. Transcriptome analysis suggested that LCT may influence AS risk by regulating the expression of genes such as Cyp3a13, Cyp2b10, Vnn1, Hsd3b5, Hsd3b2, and Gapdhs, thereby affecting metabolic processes.

Conclusion

LCT exacerbates atherosclerotic lesions in ApoE^−/−mice, and fecal metabolomic alterations may contribute to this process.

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Lambda-cyhalothrin暴露可促进ApoE - / -小鼠动脉粥样硬化的发展

氰氯氰菊酯（LCT）是一种广泛使用的拟除虫菊酯类杀虫剂，与代谢紊乱的发生有关。然而，其在动脉粥样硬化（AS）中的具体作用尚不清楚。目的研究LCT对ApoE−/−小鼠AS发展的影响，并探讨代谢组学改变在其中的潜在作用。方法8周龄ApoE−/−雄性小鼠高脂喂养12周，建立AS模型。将15只AS模型小鼠随机分为3组（每组 = 5只），进行为期15天的干预：(1)正常对照组（NC），(2) 45 %高脂饮食（HFD），(3)高脂饮食加蓝氟氯氰菊酯暴露组（HFD+LCT， 1 mg/kg/天）。干预后，收集粪便、血清和主动脉样本。使用主动脉组织油红O染色评估动脉粥样硬化病变，并测量血脂谱。使用液相色谱-质谱（LC-MS）进行粪便代谢组学分析。此外，我们还对两个独立的基因表达数据集（GSE122165和GSE124081）进行了生物信息学分析，以阐明与拟除虫菊酯暴露相关的分子途径。结果与NC组和HFD组相比，HFD+LCT组主动脉斑块形成明显增加，血清甘油三酯（TG）水平升高。非靶向代谢组学分析显示，与HFD组相比，HFD+LCT组存在实质性的紊乱，159种代谢物显著改变（108种增加，51种减少）。京都基因和基因组百科全书途径富集分析确定了9条可能参与lct加重AS的途径，包括脂质和AS，胆固醇代谢和甘油脂代谢。甘油三酯种类TG（16:0/16:1/16:1）被确定为潜在的介质。转录组分析提示LCT可能通过调节Cyp3a13、Cyp2b10、Vnn1、Hsd3b5、Hsd3b2和Gapdhs等基因的表达，从而影响AS风险，从而影响代谢过程。结论lct加重ApoE−/−小鼠的动脉粥样硬化病变，粪便代谢组学改变可能参与了这一过程。

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.