Folic acid ameliorates N-methyl-N′-nitro-N-nitrosoguanidine-induced esophageal inflammation via modulation of the NF-κB pathway

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a common alkylating agent, which can be experimentally used as a chemical mutagen and carcinogen, extensively existing in the environment. Folic acid (FA), part of the B group of vitamins, plays an important role in defending against inflammation and reducing the risk of cancers. Nevertheless, there is little research on the protective effects of FA against MNNG-induced esophageal inflammation, and its underlying mechanism still remains elusive. Hence, in the present study, we exposed MNNG to SD rats and esophageal cells to establish the esophageal inflammation models. Our research aims to explore the protective roles of FA against esophageal inflammation induced by MNNG via NF-kappa B pathway by CCK-8, EdU, RT-qPCR, ELISA, H&E, Western blot. Our results revealed that MNNG decreased the viability of esophageal cells, which was restored under FA intervention. Besides, FA relieved the elevation of IL-6, IL-8 and TNF-alpha in MNNG-induced esophageal inflammation. Moreover, histopathological analysis showed that epithelial spinous cells proliferated in mucous layer, and inflammatory cells were locally infiltrated in the submucosa after MNNG exposure, while the pathological damage of esophageal tissues was gradually alleviated along with increasing FA doses. And Western blot results demonstrated that FA could relieve the rise of phosphorylated I kappa B alpha (p-I kappa B alpha) and phosphorylated p65 (p-p65) proteins induced by MNNG. Therefore, it is reasonable to believe that FA has a crucial role in preventing MNNG-induced esophageal inflammation through inhibiting the NF-kappa B pathway, thereby down-regulating the expressions of IL-6, IL-8 and TNF-alpha.

Automated summary

In this study, it was found that folic acid (FA) effectively protected esophageal cells in the MNNG-induced esophageal inflammation model by inhibiting the NF-kappa B pathway and down-regulating the expression of inflammatory molecules IL-6, IL-8, and TNF-alpha. These findings are of great significance for further research and development of therapeutic strategies for preventing esophageal inflammation.