Imidacloprid increases intestinal permeability by disrupting tight junctions.

Area of Science:

• Environmental Toxicology
• Gastroenterology
• Molecular Biology

Background:

• Neonicotinoid pesticides like imidacloprid (IMI) are widespread environmental contaminants.
• IMI is absorbed by the intestine, but its impact on intestinal barrier function is poorly understood.

Purpose of the Study:

• To investigate the effects of IMI on intestinal epithelial barrier integrity and identify underlying molecular mechanisms.
• To assess the role of the pregnane X receptor (PXR) and myosin light chain kinase (MLCK) signaling in IMI-induced gut barrier disruption.

Main Methods:

• In vivo toxicity study in male Wistar rats (90-day repeated oral dose).
• In vitro assays using Caco-2 cell monolayers to assess barrier permeability and protein expression.
• In silico analysis to predict PXR-IMI interactions.
• Measurement of tight junction proteins, inflammatory biomarkers, and signaling pathway components (NF-κB p65, MLCK).

Main Results:

• IMI exposure significantly increased intestinal permeability, endotoxin, and inflammatory biomarkers (TNF-α, IL-1β) in rats.
• Caco-2 cells treated with IMI showed reduced transepithelial electrical resistance and tight junction protein levels.
• IMI disrupted the PXR-NF-κB p65-MLCK signaling pathway, with effects reversed by MLCK inhibitor ML-7.
• In silico analysis confirmed potent binding sites between PXR and IMI.

Conclusions:

• Imidacloprid induces intestinal epithelial barrier disruption and inflammation.
• The mechanism involves down-regulation of tight junctions and modulation of the PXR-NF-κB p65-MLCK pathway.
• IMI's impact on gut barrier integrity warrants attention for pesticide safety assessments.