Dietary Zinc Ameliorates TNBS-Induced Colitis in Mice Associated with Regulation of Th1/Th2/Th17 Balance and NF-κB/NLRP3 Signaling Pathway

Biol Trace Elem Res. 2024 Feb;202(2):659-670. doi: 10.1007/s12011-023-03715-y. Epub 2023 May 30.

Abstract

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic relapsing inflammatory gastrointestinal tract diseases of uncertain origin, which are frequently associated with zinc deficiency. Animal models have a considerable value in elucidating the process of IBD. In this study, 50 male C57BL/6 J mice were randomly assigned to five groups: control group (Con), 2,4,6-trinitrobenzenesulfonic acid (TNBS) group, and three zinc supplementation groups, namely 160 ppm group, 400 ppm group, and 1000 ppm group. The results showed that supplementation of dietary zinc with zinc oxide could effectively relieve the severity of ulcerative colitis induced by TNBS in mice. We demonstrate that the protective mechanism involves the immunomodulation of dietary zinc by increasing CD3+, CD3+CD8+, and Th2 cells, suppressing Th1 and Th17 cells, and decreasing the production of serum IL-1β and IL-18. The dietary zinc oxide seems to be able to suppress the NF-κB/NLRP3 signaling pathway by downregulating the mRNA and protein expression of NIK, IKK, NF-κB, and NLRP3. The results suggest that dietary supplementation of zinc oxide may protect against colitis, and proper daily zinc supplementation may reduce the risk of IBD.

Keywords: Colitis; Immune; Molecular mechanism; TNBS; Zinc.

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / prevention & control
  • Colitis, Ulcerative*
  • Disease Models, Animal
  • Inflammatory Bowel Diseases*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Signal Transduction
  • Th17 Cells / metabolism
  • Zinc / adverse effects
  • Zinc Oxide* / pharmacology

Substances

  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Zinc Oxide
  • Zinc