Transport mechanisms of pesticide mixtures impairing intestinal barrier function in mice

Multiple pesticide residues in the diet can be ingested through the intestine; however, the interactions affecting intestinal health remain unclear. Histopathological analysis of mouse intestines revealed synergistic damage in those exposed to a binary mixture of abamectin, fluazinam, and spirodiclofen. The combined exposure to fluazinam and spirodiclofen resulted in a 73.35 % reduction in the expression level of the tight junction protein claudin-1 in Caco-2 cells. The studies on the transport in Caco-2 cells revealed that the combined exposure to abamectin and spirodiclofen resulted in transport amounts that were 5.37 and 19.98 times greater than those observed with individual exposures, respectively. The transporter inhibitors and molecular docking analysis indicated that competitive inhibition of the breast cancer resistance protein (BCRP) led to decreased pesticide efflux. Therefore, the disruption of the intestinal barrier caused by the interaction of pesticide mixtures warrants attention when evaluating the safety of various pesticide residues.