Institute of Animal Nutrition, Northeast Agricultural University, Harbin, China.
Environ Toxicol. 2022 Aug;37(8):1878-1890. doi: 10.1002/tox.23534. Epub 2022 Apr 7.
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.
草甘膦类除草剂（GBHs）是世界上使用最广泛的农药，其广泛使用增加了对环境安全和潜在的人类和牲畜健康风险的压力。本研究探讨了 GBHs 对猪肠上皮细胞（IPEC-J2）抗氧化能力、炎症细胞因子和自噬的影响及其分子机制。同时，评估了 N-乙酰半胱氨酸（NAC）对 GBHs 毒性的保护作用。我们的结果表明，GBHs 降低了抗氧化酶（SOD、GSH-Px）的活性。GBHs 增加了炎症因子（IL-1β、IL-6、TNF-α）和 iNOS 和 COX-2 的 mRNA 表达。GBHs 诱导 Nrf2/HO-1 通路的上调和 IκB-α 和 NFκB p65 的磷酸化，LC3-II/LC3-I 的上调和 P62 的下调，NFκB 抑制剂降低了炎症细胞因子（IL-1β、IL-6、IL-8）的 mRNA 表达。此外，NAC 通过抑制 ROS 水平降低了细胞毒性，并改变了自噬相关蛋白，如抑制 LC3-II 转化和上调 P62。我们的研究结果揭示了 GBHs 对 IPEC-J2 细胞作用的新机制，NAC 可以在一定程度上逆转细胞毒性。
