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

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-1ß, 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-1ß, 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.

Toxic effects of glyphosate on intestinal morphology, antioxidant capacity and barrier function in weaned piglets.

At present, the public is paying more attention to the adverse effects of pesticides on human and animal health and the environment. Glyphosate is a broad-spectrum pesticide that is widely used in agricultural production. In this manuscript, the effects of diets containing glyphosate on intestinal morphology, intestinal immune factors, intestinal antioxidant capacity and the mRNA expression associated with the Nrf2 signaling pathway were investigated in weaned piglets. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) were randomly selected with an average weight of 12.24 ±â€¯0.61 kg. Weaned piglets were randomly assigned into 4 treatment groups and fed a basal diet supplemented with 0, 10, 20, and 40 mg/kg glyphosate for a 35-day feeding trial. We found that glyphosate had no effect on intestinal morphology. In the duodenum, glyphosate increased the activities of CAT and SOD (linear, P < 0.05) and increased the levels of MDA (linear and quadratic, P < 0.05). In the duodenum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and NQO1 (linear and quadratic, P < 0.05) and reduced the relative mRNA expression levels of GPx1, HO-1 and GCLM (linear and quadratic, P < 0.05). In the jejunum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and decreased the relative mRNA expression levels of GCLM (linear and quadratic, P < 0.05). Glyphosate increased the mRNA expression levels of IL-6 in the duodenum (linear and quadratic, P < 0.05) and the mRNA expression levels of IL-6 in the jejunum (linear, P < 0.05). Glyphosate increased the mRNA expression of NF-κB in the jejunum (linear, P = 0.05). Additionally, the results demonstrated that glyphosate linearly decreased the ZO-1 mRNA expression levels in the jejunum and the mRNA expression of claudin-1 in the duodenum (P < 0.05). In the duodenum, glyphosate increased the protein expression levels of Nrf2 (linear, P = 0.025). Overall, glyphosate exposure may result in oxidative stress in the intestines of piglets, which can be alleviated by enhancing the activities of antioxidant enzymes and self-detoxification.

Exchange Coupling in Soft Magnetic Nanostructures and Its Direct Effect on Their Theranostic Properties.

Exchange coupling between hard and soft magnetic materials at the nanoscale exhibits novel or improved physical properties for energy and data storage applications. Recently, exchange coupling has also been explored in core/shell magnetic nanostructures (MNS) composed of hard and soft magnetic spinel ferrites, but applications have been limited in biomedicine due to the presence of "toxic" cobalt based ferrites as hard magnetic component. We report core/shell MNS where both core and shell components are soft magnetic ferrites (Fe3O4, MnFe2O4, and Zn0.2Mn0.8Fe2O4) and show that exchange coupling still exists due to the difference in their anisotropy. The physical properties (saturation magnetization, susceptibility, anisotropy, r2 relaxivity, and specific absorption rate) of core/shell MNS are compared with the same size single phase counterparts which excludes any size dependent effect and gives the direct effect of exchange coupling. After optimization of core and shell components and their proportions, we have shown that a core/shell MNS shows significantly higher contrast enhancement and thermal activation properties than their single phase counterparts due to exchange coupling between core and shell ferrites. Our finding provides a novel way to improve theranostic properties of spinel ferrite based MNS while maintaining their biocompatibility.