Effects of 2,4‐dichlorophenoxyacetic acid on the expression of NLRP3 inflammasome and autophagy‐related proteins as well as the protective effect of Lycium barbarum polysaccharide in neonatal rats

Abstract

The pesticide 2,4‐dichlorophenoxyacetic acid (2,4‐D) has neurotoxic effects, but its mechanism is not clear. In this study, a 2,4‐D (75 mg/kg. b.w) exposure model was established in SD rats with colostrum. Lipopolysaccharide (1 mg/kg b.w) was used as the positive control, and Lycium barbarum polysaccharide (LBP, 50 mg/kg b.w) was used as an intervention factor to explore the neurotoxic effect of 2,4‐D and the neuroprotective effect of LBP. Our research results show that 2,4‐D causes a decrease in the number of hippocampal CA3 pyramidal cells and pyknosis in nuclei with a triangular or irregular shape and that rats show signs of anxiety or depression. In rat serum, superoxide dismutase, and glutathione peroxidase activity decreased, while malondialdehyde content increased. Protein and mRNA levels of TNFα, IL‐6, IL‐1β, IL‐18, NLRP3, ASC, caspase‐1, IL‐1β, IL‐18, and p62 increased, while those of LC3‐II/LC3‐I and Beclin‐1 decreased in hippocampal tissues. In conclusion, 2,4‐D increased the oxidative stress level, induced neuroinflammatory response, and decreased the autophagy level in experimental rats. LBP may have upregulated the autophagy level in the body by inhibiting the activation of the NLRP3 inflammasome, thus playing a neuroprotective role.

Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating α7nAChR‐mediated microglial polarization

“…Autophagy is an evolutionarily conserved metabolic process that promotes the recovery and degradation of intracellular macromolecules and damaged organelles 41,42 . α7nAChR mediated autophagy activation is associated with the progression of multiple inflammatory diseases.…”

“…23 In this study, we found that Autophagy is an evolutionarily conserved metabolic process that promotes the recovery and degradation of intracellular macromolecules and damaged organelles. 41,42 α7nAChR mediated autophagy activation is associated with the progression of multiple inflammatory diseases. It was reported that the α7nAChR agonist PNU282987 alleviates nerve injury in tMCAO mice by enhancing autophagy and promoting autophagy flux.…”

2,4‐dichlorophenoxyacetic acid induces ROS activation in NLRP3 inflammatory body‐induced autophagy disorder in microglia and the protective effect of Lycium barbarum polysaccharide

“…2,4‐Dichlorophenoxyacetic acid (2,4‐D) exerts neurotoxic effects that may lead to cell death by inducing oxidative stress in cells via the release of reactive oxygen species (ROS) in excess 1–3 . We previously showed that 2,4‐D increased the oxidative stress level, induced neuroinflammatory response, and decreased the autophagy level in experimental rats, 4 however, the specific mechanism underlying its toxicity remains to be clarified. Recent studies have shown that excess ROS release can activate nod‐like receptor protein 3 (NLRP3) inflammasomes 5–7 which has also been linked to various diseases, including neurodegenerative diseases.…”