Interaction of Helicobacter pylori eradication and non-steroidal anti-inflammatory drugs on gastric epithelial apoptosis and proliferation: implications on ulcerogenesis

Aliment Pharmacol Ther. 2000 Jul;14(7):879-85. doi: 10.1046/j.1365-2036.2000.00783.x.


Background: Apoptosis is associated with loss of gastric mucosal integrity and may play an important role in ulcer development.

Aim: To examine how Helicobacter pylori and NSAIDs interact to effect apoptosis and proliferation of the gastric mucosa.

Methods: Patients presenting with musculoskeletal pain requiring NSAID treatment and without previous exposure to NSAID or pre-existing ulcers were recruited. Patients were divided into three groups: (A) H. pylori-infected; (B) H. pylori-eradicated; and (C) non-infected patients. They were given naproxen for 8 weeks. Patients with non-ulcer dyspepsia and H. pylori infection who were given anti-Helicobacter therapy were recruited as controls (D). Endoscopy was performed at baseline and 8-weeks after receiving naproxen. Gastric antral biopsies were obtained to assess apoptosis by terminal uridine deoxynucleotidyl nick end-labelling (TUNEL) and proliferation by Ki67 immunostaining.

Results: A total of 55 patients were studied. H. pylori-positive patients had a higher apoptosis and proliferation index at baseline than non-infected patients (P < 0.0001), and eradication of H. pylori resulted in a significant reduction in these parameters. The NSAID induced apoptosis in non-infected subjects (P=0.03) whilst apoptosis was reduced in H. pylori-positive patients receiving NSAID (P=0.02). After 8 weeks of NSAID, post-treatment apoptosis was significantly higher in patients with persistent H. pylori infection than in non-infected patients (P=0.01).

Conclusions: Eradication of H. pylori prior to NSAID therapy significantly reduces the level of apoptosis in the gastric mucosa, which may contribute to maintaining mucosa integrity and preventing ulcer development.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Ulcer Agents / therapeutic use
  • Apoptosis*
  • Cell Division / drug effects
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / pathology
  • Helicobacter Infections / complications*
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / pathology
  • Helicobacter pylori
  • Humans
  • Male
  • Middle Aged
  • Stomach Ulcer / etiology*
  • Stomach Ulcer / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents