The Gastrin Receptor Antagonist Netazepide (YF476) Prevents Oxyntic Mucosal Inflammation Induced by Helicobacter Pylori Infection in Mongolian Gerbils

ObjectiveLong-term Helicobacter pylori infection causes gastritis leading to hypergastrinemia and predisposes to gastric cancer. Our aim was to assess the role of gastrin in oxyntic mucosal inflammation in H.pylori-infected Mongolian gerbils by means of the gastrin receptor antagonist netazepide (YF476). DesignWe studied 60 gerbils for 18months and left five animals uninfected (control group), inoculated 55 with H.pylori, and treated 28 of the infected animals with netazepide (Hp+YF476 group). Twenty-seven infected animals were given no treatment (Hp group). We measured plasma gastrin and intraluminal pH. H.pylori detection and histologic evaluations of the stomach were carried out. ResultsAll 55 inoculated animals were H.pylori positive at termination. Eighteen animals in the Hp group had gastritis. There was a threefold increase in mucosal thickness in the Hp group compared to the Hp+YF476 group, and a threefold increase in oxyntic neuroendocrine cells in the Hp group compared to the Hp+YF476 group (p<.05). All animals in the Hp+YF476 group had macro- and microscopically normal findings in the stomach. Plasma gastrin was higher in the Hp group than in the control group (17216pmol/L vs 124 +/- 5pmol/L, p<.05) and highest in the Hp+YF476 group (530 +/- 36pmol/L). Intraluminal pH was higher in the Hp group than in the Hp+YF476 group (2.51 vs 2.30, p<.05). ConclusionThe gastrin antagonist netazepide prevents H.pylori-induced gastritis in Mongolian gerbils. Thus, gastrin has a key role in the inflammatory reaction of the gastric mucosa to H.pylori infection in this species.