Effect of tegoprazan, a novel potassium-competitive acid blocker, on non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy

Sci Rep. 2024 Nov 8;14(1):27173. doi: 10.1038/s41598-024-78581-2.

Abstract

As the non-steroidal anti-inflammatory drugs (NSAIDs) are typically used in the treatment of chronic conditions, the incidence of NSAID-induced enteropathy is increasing. Given the challenges associated with discontinuing NSAIDs, effective preventive and treatment strategies are crucial. We assessed the effect of tegoprazan on NSAID-induced enteropathy. Human epithelial cells (HIEC-6, HT-29, and Caco-2) were treated with indomethacin and tegoprazan. Cell viability, expression levels of tight-junction proteins, levels of proinflammatory cytokines, and apoptosis were assessed by conducting MTT assays, RT-PCR, western blotting, and immunofluorescence staining, respectively. Tegoprazan significantly ameliorated the inhibition of cell proliferation induced by indomethacin. Tegoprazan also mitigated the suppression of occludin and ZO-1 expression by indomethacin, thereby restoring intestinal permeability. Additionally, tegoprazan reversed the indomethacin-induced elevation of the levels of proinflammatory cytokines and the rate of apoptosis of small intestinal epithelial cells. Our findings indicate that tegoprazan exerts a protective effect against NSAID-induced injury to small intestinal epithelial cells. The effect involves enhancement of the expression levels of tight junction proteins and the suppression of inflammation and apoptosis.

Keywords: Enteropathy; Non-steroidal anti-inflammatory drug; Permeability; Tegoprazan.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Apoptosis* / drug effects
  • Caco-2 Cells
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • HT29 Cells
  • Humans
  • Indomethacin* / adverse effects
  • Intestinal Diseases / chemically induced
  • Intestinal Diseases / drug therapy
  • Intestinal Diseases / metabolism
  • Intestinal Diseases / pathology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Tight Junction Proteins / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin
  • Cytokines
  • Tight Junction Proteins