Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett’s esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.
The metabolic relationship between H2S and NO in gastric mucosa in norm and pathology is still poorly studied. Aim of this study was to determine mechanisms of interaction between NO and H2S generating systems under conditions of the combined actions of NSAIDs and stress. Water restraint stress (WRS) was used to induce peptic lessions in rats; naproxen and ATB-346 were administered prior to WRS. Nos2, Cbs and Ptgs2 gene expression level was determined by semiquantitative RT-PCR in gastric epitheliocytes. In the gastric mucosa were determined: alterations in H2S and NOx concentrations, changes in activity of myeloperoxidase. Both WRS and naproxen action prior to WRS cased a significant rise in myeloperoxidase activity. Administration of ATB-346 resulted in a considerable decrease of myeloperoxidase activity. Naproxen action caused the downregulation of Nos2. The level of Cbs expression in group pretreated with naproxen was much higher than in group of WRS alone. We suppose that it increases as a result of Nos2 downregulation and the correspondent decrease of NO concentration. The relationship between NO and H2S in the gastric mucosa is likely mediated through the regulation of genes expression. As a result of the released H2S, ATB-346 administration decreased the severity of gastric mucosa lesions.
The present study was designed to evaluate the role of postprandial hyperglycemia (PHG) on oesophageal epithelial barrier (OEB) integrity via evaluation expression of fucosylated glycans by PFA and LABA labeling and mechanism in formation PHG induced pre-ulcer lesions through the NO/NOS activity in OEB and therapeutic potential and mechamism of L-Tryptophan influence on OEB lesions. Fucosaylated glycans are contributed in OEB integrity. NO/NOS activity seem to play a critical role in OEB ulcerogenesis because blocking its activity aggravates experimental OEB lesions, most likely through the inflammation, vascular and perivascular changes.
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