Work

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

Year: 2025

Type: article

Abstract: 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. This study aimed to investigate the influence of LCT on AS development in ApoE −/− mice and to explore the potential role of metabolomic alterations. 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. 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. LCT exacerbates atherosclerotic lesions in ApoE −/− mice, and fecal metabolomic alterations may contribute to this process. Schematic overview of the study design. LCT, Lambda-cyhalothrin; AS, Atherosclerosis; HFD, High-fat diet; NC, Normal control; TG, Triglyceride; TC, Total cholesterol; LDL-C, Low-density lipoprotein cholesterol; HDL-C, High-density lipoprotein cholesterol; LC-MS, Liquid Chromatography-Mass Spectrometry. ● First exploration of the effect of lambda-cyhalothrin on the development of atherosclerosis. ● lambda-cyhalothrin enhanced atherosclerotic plaque formation and dyslipidemia in ApoE −/− mice. ● Fecal metabolites may play a role in this enhancement of atherosclerosis.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119165