Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

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 H(2)S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H(2)S 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 H(2)S synthesis or of an H(2)S 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 H(2)S 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 H(2)S 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. H(2)S contributes significantly to mucosal defence in the esophagus, and H(2)S donors may have therapeutic value in treating esophageal inflammation and injury.