Emamectin benzoate-induced toxicity affects intestinal epithelial integrity involving apoptosis

• Published in: Food and chemical toxicology Vol. 190; p. 114827
• Main Authors: Yue, Xingyu, Lin, Fengxiang, Gui, Shuyan, Zhang, Sai, Wu, Zongbin, Xiang, Yuxin, Xiao, Tianxiang, Xiao, Jinjing, Cao, Haiqun, Shi, Yanhong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2024
• Subjects: Apoptosis; Apoptosis - drug effects; Caco-2 Cells; Caco-2 cell; Cell Survival - drug effects; Emamectin benzoate; Humans; Intestinal epithelial barrier; Intestinal Mucosa - drug effects; Ivermectin - analogs & derivatives; Ivermectin - toxicity; RNA-Seq; Transcriptome - drug effects; Caco-2 cell; RNA-Seq; Intestinal epithelial barrier; Emamectin benzoate; Apoptosis
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.114827

The frequency presence of emamectin benzoate in agricultural production highlights the need for studying their toxicity against human intestinal epithelial barrier (IEB). Herein, we combined a Caco-2 cell model with transcriptome analysis to assess the intestinal toxicity of emamectin benzoate and its disease-causing potential. Results showed that the half maximal inhibitory concentration (IC50) of emamectin benzoate on Caco-2 cell viability after 24, 48, and 72 h of exposure were 18.1, 9.9, and 8.3 μM, respectively. Emamectin benzoate exposure enhanced the Caco-2 monolayer paracellular permeability, damaged the IEB, and increased cellular apoptosis. Key driver gene analysis of 42 apoptosis - related DEGs, identified 10 genes (XIAP, KRAS, MCL1, NRAS, PIK3CA, CYCS, MAPK8, CASP3, FADD, and TNFRSF10B) with the strongest correlation with emamectin benzoate - induced apoptosis. Transcriptomics identified 326 differentially expressed genes (DEGs, 204 upregulated and 122 downregulated). The functional terms of neurodegeneration - multiple diseases was enriched with the most number of DEGs, and the Parkinson disease pathway had the highest enrichment degree. Our findings provided support for environmental toxicology studies and the health risk assessment of emamectin benzoate. [Display omitted]