Imidacloprid increases intestinal permeability by disrupting tight junctions

• DOI: 10.1016/j.ecoenv.2021.112476
• Publication Date: 2021-06-30T00:58:07Z
• Authors: Guo-Ping Zhao; Xiao-Yu Wang; Jin-Wang Li; Ran Wang; Fa-Zheng Ren; Guo-Fang Pang; Yi-Xuan Li
• Keywords: Caco-2; Pregnane X receptor; Intestinal Permeability; Paracellular transport; Intestinal mucosa; Occludin

The neonicotinoid pesticide, imidacloprid (IMI), is frequently detected in the environment and foods. It absorbed metabolized by intestine; however, its effects on intestinal barrier integrity are not well studied. We investigated whether IMI disrupts permeability of epithelial via vivo tests male Wistar rats, vitro assays using human cell line, Caco-2, silico analyses. A repeated oral dose 90-day toxicity study was performed (0.06 mg/kg body weight/day). exposure significantly increased permeability, which led to elevated serum levels endotoxin inflammatory biomarkers (tumor necrosis factor-alpha interleukin-1 beta) without any variation weight. Decreased transepithelial electrical resistance with also observed 100 nM μM IMI-treated Caco-2 monolayers. Amounts tight junction proteins colon tissues between cells were lower than those controls. Increased myosin light chain phosphorylation, kinase (MLCK), p65 subunit nuclear factor kappa-light-chain-enhancer activated B (NF-κB p65) phosphorylation found IMI-exposed compared control cells. Furthermore, loss caused rescued MLCK inhibitor, ML-7, cycloheximide. Pregnane X receptor (PXR, NR1I2) inhibited low-dose treatment. In analysis indicated potent binding sites PXR IMI. Together, these data illustrate that induces disruption produces an response, involving down-regulation junctions disturbance PXR-NF-κB p65-MLCK signaling pathway. deserves attention assessing safety this pesticide.