Mechanism of nonylphenol induced gastric inflammation through NF-κB/NLRP3 signaling pathway

Abstract

Studies have found that the intake of environmental endocrine disruptors was positively correlated with the occurrence of gastric diseases. The aim of this study was to determine whether nonylphenol (NP) exposure can induce gastric inflammation and whether its mechanism was related to NF-κB/NLRP3 signaling pathway. In vivo, male SD rats were randomly divided into 4 groups (12 rats/group): control group (corn oil), NP low (0.4 mg/kg), medium (4 mg/kg), and high (40 mg/kg) dose groups. After 33 weeks of NP chronic exposure, it was found pathological changes in gastric tissues, increase the release of inflammatory factors, and effects expressions of genes related to the NF-κB/NLRP3 signaling pathway. In vitro, the GES-1 cell experiments, which included four groups: control (0 µmol/L NP), L (2.5 µmol/L NP), M (40 µmol/L NP), and H (60 µmol/L NP), confirmed that NP increased the release of inflammatory factors in the cells, and up-regulated the expression of proteins related to NF-κB/NLRP3 signaling pathway. Furthermore, when pyrrolidinedithiocarbamate ammonium (PDTC) blocked the NF-κB signaling pathway, it was found that the expression of related proteins in the NF-κB/NLRP3 signaling pathway was decreased, and the release of inflammatory factors in GES-1 cells caused by NP was also attenuated. The results of this study indicated that NP can induce inflammation in the stomach in vivo and in vitro, and its mechanism was related to the NF-κB/NLRP3 signaling pathway. These findings provided a new perspective on the mechanism of inflammatory response induced by exposure to environmental endocrine disruptors. Also, these findings indicated that therapeutic strategies for the NF-κB/NLRP3 signaling pathway may be new methods to treat inflammatory diseases.