Glyphosate‐based herbicides induces autophagy in IPEC‐J2 cells and the intervention of N‐acetylcysteine

Abstract Glyphosate‐based herbicides (GBHs) are the most widely used pesticide in the world, and its extensive use has increased pressures on environmental safety and potential human and livestock health risks. This study investigated the effects of GBHs on antioxidant capacity, inflammatory cytokines, and autophagy of porcine intestinal epithelial cells (IPEC‐J2) and its molecular mechanism. Also, the protective effects of N‐acetylcysteine (NAC) against the toxicity of GBHs were evaluated. Our results showed that the activities of antioxidant enzymes (SOD, GSH‐Px) were decreased by GBHs. GBHs increased inflammatory factors (IL‐1β, IL‐6, TNF‐α) and the mRNA expression of iNOS and COX‐2. GBHs induced the up‐regulation of Nrf2/HO‐1 pathway and the phosphorylation of IκB‐α and NFκB p65, up‐regulation of LC3‐II/LC3‐I, and down‐regulation of P62, and NFκB inhibitor decreased the mRNA expression of inflammatory cytokines (IL‐1β, IL‐6, IL‐8). Moreover, NAC reduced the cytotoxicity by suppressing ROS levels, and changed the autophagy‐related proteins such as the suppression of LC3‐II conversion and up‐regulation of P62. Our findings unveil a novel mechanism of GBHs effects on IPEC‐J2 cells and NAC can reverse cytotoxicity to some extent.