Glycine alleviates the intestinal epithelial barrier damage induced by imidacloprid via promoting metabolic detoxification

Imidacloprid, a neonicotinoid pesticide that was reported to induce intestinal damage at low doses, necessitating effective intervention strategies. As a common component in food, glycine (GLY) has the capacity to alleviate intestinal damage. However, whether it can relieve the damage caused by imidacloprid leave to be clarified. This study investigated the protective effects of GLY (2% and 5%) against imidacloprid induced (0.06 mg/kg bw/day) intestinal injury in male Wistar rats. GLY supplementation attenuated intestinal permeability and enhanced the expression of tight junction proteins. Further, the pregnane X receptor-myosin light chain 2 signaling pathway that mediating imidacloprid-induced intestinal toxicity was also found repaired. GLY intervention increased the enzyme activities of cytochrome P450 3A4 and glutathione-S-transferase, which were responding for phase I and phase Ⅱ imidacloprid metabolism. Meanwhile, reduced levels of imidacloprid and its phase I metabolites, as well as increased phase Ⅱ detoxifying glutathione conjugates, both suggesting the protective role of GLY intervention through enhancing imidacloprid detoxification metabolism. Importantly, the amino acid signaling pathway related fecal metabolic profiles and microbiota composition in imidacloprid treated rats were also modulated and improved by GLY. Totally, our findings demonstrated the protective effect of GLY on intestinal damage caused by imidacloprid exposure, which provided ideas for preventing and controlling the toxicity of food contaminants. • Dietary intervention with glycine is a potential strategy to mitigate imidacloprid induced toxicities • Glycine can alleviate imidacloprid-induced intestinal injury through upregulation of tight junction proteins. • Glycine could promote metabolic detoxification of imidacloprid via increasing phase II detoxifying glutathione conjugates. • Glycine supplementation restores imidacloprid-induced metabolic dysregulation and gut microbiota disruption.