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

• Published in: Journal of hazardous materials Vol. 387; p. 121707
• Main Authors: Fu, Huiyang, Qiu, Shengnan, Yao, Xinxin, Gao, Feng, Tan, Peng, Teng, Teng, Shi, Baoming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-04-2020
• Subjects: Animal Feed; Animals; Antioxidant; CAR/PXR; Constitutive Androstane Receptor; Female; Food Contamination; Gene Expression - drug effects; Glycine - analogs & derivatives; Glycine - toxicity; Glyphosate; Herbicides - toxicity; Keap1-Nrf2; Kelch-Like ECH-Associated Protein 1 - metabolism; Liver - drug effects; Liver - pathology; NF-E2-Related Factor 2 - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Glucocorticoid - metabolism; Signal Transduction - drug effects; Swine; Weaned piglets; ADG; ALP; ALT; GLP; MDA; H2O2; Glyphosate; GLU; CHOL; GPX1; P-gp; CAR/PXR; IW; CAR; TBIL; CAT; ADFI; Keap1-Nrf2; CYP2E1; DBIL; F/G; GSH-Px/GPx; HO-1; PXR; CYP2A19; URIC; FW; HDL; LDH; MDR1; CREA; LDL; BUN; GSH; UGT1A6; NQO1; AST; MRP2; Weaned piglets; CK; T-AOC; SOD; GST; SOD2; Antioxidant; SOD1; CYP3A29; GCLC; TG; GGT; GSTA2; ALB; CYP1A2; GSTA1; Keap1; CYP1A1; A/G; TP; GLB; GCLM; NFE2L2
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2019.121707

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•Glyphosate (GLP) is the herbicide with the largest dosage and yield in production.•It is unprecedented to take sensitive weaned piglets as the research object of GLP test.•The intake of GLP has no effect on the performance of weaned piglets•GLP intake can cause changes in antioxidant enzymes activity.•The toxicity can be alleviated by activating the nuclear receptor CAR/PXR signaling 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.