Exogenous luminal nitric oxide exacerbates esophagus tissue damage in a reflux esophagitis model of rats

Abstract

Exogenous luminal nitric oxide greatly exacerbated the tissue damage of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent superoxide-enriched inflamed tissue of the esophagus could lead to the production of the highly toxic agent peroxynitrite, thus causing exacerbation of the esophageal damage.

Oxidative Stress and Protective Effect of Erythropoietin on Methotrexate-induced Esophageal Damage

“…3,4 Free oxygen radicals or reactive oxygen species (ROS) play an important role in the acute stage of esophageal burn and reflux esophagitis. [5][6][7] ROS, in particular superoxide anion (O 2 À ), play an important role in the pathogenesis of esophagitis induced by acid and pepsin. 7 The role of oxidative stress in MTX-induced small intestinal toxicity has been researched and found that animals that received N-acetylcysteine or tungsten showed a decreased production of ROS and decreased myeloperoxidase activity.…”

Oral Nitrate Reductase Activity and Erosive Gastro-esophageal Reflux Disease: A Nitrate Hypothesis for GERD Pathogenesis

“…Ishiyama et al have shown that co-administration of sodium nitrite and ascorbic acid increased reflux-induced esophageal damage fourfold to fivefold in mice, while neither of the agents alone could do so. Their data suggested that this damage was mediated by the interaction of nitric oxide and superoxide species giving rise to the highly noxious peroxynitrite [15]. In another study, Ito et al demonstrated that DIS, a characteristic histological finding of reflux esophagitis, can be induced in rat esophageal epithelium by exposing it to sodium nitrite and acid but not acid alone [16].…”

“…Recent ecologic data have linked high nitrate content of drinking water to increased prevalence of acid regurgitation [14]. In addition, animal studies have shown that when reflux is induced in mice, they develop significant esophagitis only when fed a diet containing nitrates [15]. It has also been shown that dilated intercellular space (DIS), a basic histological characteristic of the lower esophagus in GERD, is induced by nitrates and acid, but not by acid alone [16].…”

Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis

“…34,35 It was reported that exogenous luminal NO exacerbates tissue damage in a RE model of rats. 36 In esophageal cells, iNOS was up-regulated by common reflux constituents, leading to NO production. 37 Diffusion of the luminal NO into ), 3-NT (C) levels, and MDA levels (D) of esophagus.…”