Acid Inhibitors Exacerbate H.pylori‐Induced Gastritis Both In Vitro And In Vivo

Abstract

BackgroundGastric cancer (GC) is strongly associated with H.pylori infection. But, GC tends to develop in hypochlorhydric, but not in hyperchlorhydric patients. Since potent acid inhibitors, such as proton pump inhibitors (PPI) are widely used for the treatment of GERD, it seems reasonable to assume that potent acid inhibitors may excerbate H.pylori‐induced gastritis, promote gastric atrophy, and increase risk of GC. Based on these hypothesis, we examined (1) if the increased gastric luminal pH enhances toxicity of H.pylori‐derived ammonia in vitro, (2) if PPIs exacerbates gastritis in H.pylori‐infected mice in vivo.MethodsA:In vitro study: 1. Intact sheets of in vitro bullfrog gastric mucosa were incubated in Ussing chambers in vitro. Transmucosal electrical resistance (TER) was monitored to evaluate mucosal integrity. 2. GSM06 cells, derived from murine gastric mucosa, were cultured with or without 5 mM NH4Cl. Cell viablity and gastric mucosal apoptosis were evaluated by MTT, and by capase‐3 assay, respectively. B: In vivo study: Six‐wk‐old female mice were cultured for 8 wks after inoculated with H.pyloi, SS‐1. Degree of gastritis was evaluated using updated Sydney sysytem. Colonization of H.pylori was also examined.ResultsA‐1. NH4Cl decreased TER at high luminal pH (>7.0), but not at low luminal pH (5.0). A‐2. NH4Cl decreased cell viality and enhanced apoptosis more at higher ambient pH (7.8), than at low pH (7.2). B‐1. PPI Tx exacerbated inflammation in corpus, but not in antral mucosa in H.pylori‐infected mice. B‐2. PPI Tx increased colonization of H.pylori only in corpus.ConclusionsHigh ambient pH induced by potent acid inhibitors enhances toxicity of H.pylori‐dervied ammonia, thereby exacerbates H.pylori‐induced gastritis. Potent acid inhibition may increase risk of GC in patients with H.pylori infection.