New Frontiers in Gut Nutrient Sensor Research: Prophylactic Effect of Glutamine Against Helicobacter pylori–Induced Gastric Diseases in Mongolian Gerbils

Abstract

Abstract. Ammonia is one of the important toxins produced by Helicobacter pylori (H. pylori), the major cause of peptic ulcer diseases. We examined whether glutamine or marzulene (a gastroprotective drug containing 1% sodium azulene and 99% glutamine) protects the gastric mucosa against H. pylori in vivo and investigated the mechanism underlying glutamine-induced mucosal protection against ammonia in gastric epithelial cells in vitro. Mongolian gerbils were fed for 3 months with a diet containing glutamine (2% -20%) or marzulene (20%) starting from 2 weeks or 2 years after H. pylori infection. Then, gastric mucosal changes were evaluated both macro-and microscopically. Cultured gastric epithelial cells were incubated in the presence of ammonia, with or without glutamine; and cell viability, ammonia accumulation, and chemokine production were determined. Gerbils exhibited edema, congestion, and erosion after 3-month infection; and after 2-year infection, they showed cancer-like changes in the gastric mucosa. Glutamine and marzulene significantly suppressed these pathological changes caused in the gastric mucosa by H. pylori infection. Ammonia was accumulated in the cells, resulting in an increase in chemokine production and a decrease in cell viability. These pathological responses were prevented by glutamine. In addition, glutamine decreased chemokine production and cell death through inhibition of cellular accumulation of ammonia, resulting in the prevention of H. pylori-induced gastric diseases in vivo. These results suggest that glutamine/marzulene would be useful for prophylactic treatment of H. pylori-induced gastric diseases in patients.

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

“…We previously reported that both glutamine and MSG protected gastric epithelial cells against ammonia-induced cell death (5), and indeed, they were effective against H. pylori-induced diseases in vivo (6). Akiba et al (7,8) recently reported that MSG protected the duodenal mucosa against acid by enhancing the secretion of mucus/ bicarbonate, probably mediated by multiple glutamate receptors and suggested the importance of the chemosensing system to the duodenal mucosal defense.…”

N-methyl d-Aspartate Channels Link Ammonia and Epithelial Cell Death Mechanisms in Helicobacter pylori Infection

“…Alternatively, it was suggested that A/A accelerates the conversion of glutamine to glutamate by glutamine synthetase, which depletes cells of ATP and reduces cell viability 17 . It is not fully understood why the viability of many cancer-derived epithelial cells is not affected by A/A when compared to non-transformed cells incubated with the same dose and time 18–20 . Thus, we asked whether specific mechanisms exist to render non-transformed epithelial cells susceptible to ammonia cytotoxicity that are modified in gastric cancer.…”

L-Glutamine Eradicates Helicobacter Pylori Gastritis: A Novel Case Report

“…The antioxidant properties of L -glutamine have been claimed to be useful in the treatment of peptic ulcer disease in animal Case Report studies as well in very few human studies. Only a few animal studies have been conducted so far to investigate the role L-glutamine in the treatment of H. pylori infections and it was found to be positive, yet human trials have not been done in large scale [10]. As evidence says, glutamine helps in reducing the accumulation of ammonia in gastric tissue and cells as well it helps in reducing the oxidative free radicals in gastric tissue thereby controlling the changes induced by H. pylori infection in gastric epithelial cells [9].…”