Melatonin alleviates chronic intermittent hypoxia-induced gastric mucosal injury via attenuation of oxidative stress and JNK-mediated apoptotic signaling in rats

PLoS One. 2026 Jan 13;21(1):e0338391. doi: 10.1371/journal.pone.0338391. eCollection 2026.

Abstract

Background: To investigate the mechanism of chronic intermittent hypoxia on gastric injury in rats and the intervening effect and possible mechanism of melatonin.

Methods: Forty-eight male Wistar rats were randomly divided into normal control, intermittent hypoxia, and melatonin treatment groups. Subgroups (n = 4 per time point) were treated for 2, 4, 6, and 8 weeks. Gastric tissue morphology, gastric juice pH, pepsin levels, oxidative stress markers (MDA and SOD), and the expression of JNK and apoptosis-related genes (Bax, Bcl-2) were assessed.

Results: The intermittent hypoxia group exhibited significant gastric mucosal damage, decreased pH, increased pepsin, elevated MDA, reduced SOD, and upregulation of JNK and Bax/Bcl-2 mRNA ratio. Melatonin treatment markedly alleviated these pathological and molecular changes compared to the intermittent hypoxia group (P < 0.05).

Conclusion: Chronic intermittent hypoxia induces gastric mucosal injury, which is associated with oxidative stress imbalance and activation of JNK-mediated apoptotic signaling. Melatonin exerts a protective effect by enhancing antioxidant capacity and suppressing the JNK-Bax/Bcl-2 pathway.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis* / drug effects
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / injuries
  • Gastric Mucosa* / metabolism
  • Gastric Mucosa* / pathology
  • Hypoxia* / complications
  • Hypoxia* / metabolism
  • Hypoxia* / pathology
  • MAP Kinase Signaling System* / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Melatonin* / pharmacology
  • Oxidative Stress* / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Melatonin
  • bcl-2-Associated X Protein
  • Antioxidants
  • Proto-Oncogene Proteins c-bcl-2
  • Superoxide Dismutase
  • Malondialdehyde