Oxidative stress is more important than acid in the pathogenesis of refluxoesophagitis in rats

Background-Although antisecretory medications such as histamine type II rec eptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete muc osal healing or suffer from either sustained symptoms or ensuing complicati ons, suggesting other damaging factors or impaired mucosal resistance are a lso involved in the pathogenesis of reflux oesophagitis. Aims-The present study was designed to evaluate oxidative stress as the maj or pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis. Materials and methods-Reflux oesophagitis was induced by insertion of a 3 m m calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats. Results-DA-9601, a novel antioxidant substance, significantly attenuated th e gross and histopathological scores of reflux oesophagitis compared with t hose treated with ranitidine alone or reflux oesophagitis controls in a dos e dependent manner. Only scattered erosions were observed in the antioxidan t pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amo unts of malondialdehyde (MDA), increased nuclear factor kappaB (NF kappaB) activation, and depletion of reduced glutathione (GSH) were observed in exp erimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated th e decrement in mucosal GSH levels and decreased MDA formation significantly . DA-9601 treatment caused significant reductions in activation of NF kappa B transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NF kappaB expression. Conclusion-Reflux oesophagitis caused considerable levels of oxidative stre ss in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophag itis with acid suppression.