Folic Acid Attenuates N-Methyl-N'-Nitro-N-NitrosoguanidineInduced Gastric Mucosal Injury in Rats

Turk J Gastroenterol. 2024 Nov 1;35(11):839-848. doi: 10.5152/tjg.2024.23506.

Abstract

Background/aims: N-Methyl-N'-nitroso-N-nitrosoguanidine (MNNG) is suspected to increase the risk of developing stomach cancer. Folic acid (FA) is familiar with decreasing inflammation. We expected that FA would protect against MNNG-induced gastric mucosal injury.

Materials and methods: Thirty 12-week-old SPF-grade female Sprague-Dawley (SD) rats were treated with MNNG and given different dosages of FA as an intervention measure. Quantitative polymerase chain reaction (qPCR) was used to analyze the expression of IL-1, IL-6, IL-8, IL-18, TNF-α, NLRP3, ASC, and caspase-1 genes. The enzyme-linked immunosorbent assay (ELISA) was utilized for the identification of inflammatory cytokines. Western blot was accustomed to detecting IL-1β, IL-18, and NLRP3 inflammatory vesicles in gastric tissue. Furthermore, the gastric mucosal tissues underwent histological examination.

Results: Our investigation demonstrated that FA reduced MNNG-induced inflammatory factor increase by decreasing NF-κB signaling (P < .05). Furthermore, FA prevented the MNNG-induced upregulation of NLRP3 inflammasome-related genes and proteins (all P < .01).

Conclusion: Our data imply that MNNG exposure stimulates the NF-κB/NLRP3 pathway, while FA suppresses it, limiting stomach mucosal inflammation.

Keywords: Chemoprevention; N-methyl-N’-nitro-N-nitrosoguanidine; NF-κB/NLRP3; folic acid; stomach.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Female
  • Folic Acid* / pharmacology
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / metabolism
  • Gastric Mucosa* / pathology
  • Interleukin-18 / metabolism
  • Methylnitronitrosoguanidine* / toxicity
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Rats
  • Rats, Sprague-Dawley*

Substances

  • Methylnitronitrosoguanidine
  • Folic Acid
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Cytokines
  • NF-kappa B
  • Interleukin-18
  • Nlrp3 protein, rat