Octreotide-based therapies effectively protect mice from acute and chronic gastritis

Eur J Pharmacol. 2022 Aug 5:928:174976. doi: 10.1016/j.ejphar.2022.174976. Epub 2022 Apr 26.

Abstract

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.

Keywords: Acute and chronic gastric injury; Anti-inflammation; Drug combinations; Gastric mucosa restoration; Octreotide.

MeSH terms

  • Animals
  • Clarithromycin / metabolism
  • Clarithromycin / pharmacology
  • Clarithromycin / therapeutic use
  • Ethanol / pharmacology
  • Gastric Mucosa
  • Gastritis* / drug therapy
  • Gastritis* / prevention & control
  • Gastritis, Atrophic* / drug therapy
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Inflammation / drug therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Octreotide / pharmacology
  • Octreotide / therapeutic use
  • Omeprazole / pharmacology
  • Omeprazole / therapeutic use

Substances

  • Ethanol
  • Clarithromycin
  • Omeprazole
  • Octreotide