Toxicity of glyphosate in feed for weanling piglets and the mechanism of glyphosate detoxification by the liver nuclear receptor CAR/PXR pathway

Glyphosate (GLP), the most widely used and productive pesticide worldwide, which safety and reliability gradually become a social concern. It is important to explore the toxic of GLP on the limitation level by governments on piglets and the potential role of hepatic CAR/PXR and Keap1-Nrf2 pathways in low levels of glyphosate detoxification. Compared with the control group, the production performance and organ index of GLP group showed no significant change. However, the liver GLP residue of 40 mg/kg group was significantly higher than the control group. We also found that the activity of ALP increased linearly and DBIL content increased quadratically. Furthermore, GLP could significantly increase SOD and GSH-Px and decrease T-AOC and CAT activities and significantly increase MDA and H2O2 contents (P < 0.05); however, the genes expression of Keap1/Nrf2 pathway was not affected. Gene expression of CAR/PXR pathway showed that GLP could significantly stimulate the expression of CAR, but it could not affect the expression of phase Ⅰ (CYP1A1, CYP1A2, CYP2E1, CYP2A19, CYP3A29), phase Ⅱ (UGT1A6, GSTA1, GSTA2) detoxification enzymes and transporters (MDR1, MRP2, P-gp). Our study showed that although 10-40 mg/kg GLP would inevitably cause some liver damage and dysfunction, it can self-alleviating the toxic effect of GLP.