Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett's esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants

Oxidative damage has long been related to mucosal damages of gastrointestin al tracts and their ensuing carcinogenesis. In spite of treatment with anti -secretory medications for reflux esophagitis, considerable portions of pat ient did not achieve the complete mucosal healings or suffered from sustain ing symptoms or development of dread complication like Barrett's esophagus, suggesting other damaging factors or impaired mucosal resistance are also involved in their pathogenesis. The present study was designed either to ev aluate the oxidative stress as the major pathogenic factor of reflux esopha gitis or to find out the usefulness of antioxidant in the treatment of refl ux esophagitis and the prevention of development of Barrett's s esophagus. Acute or chronic reflux esophagitis was induced through either narrowing th e third portion of duodenal lumen or performing myotomy of lower esophageal sphincter in rats, respectively. DA-9601, a new phytopharmaceutical posses sing antioxidative properties, significantly attenuated the gross and histo pathologic scores of acute reflux esophagitis in a dose-dependent manner co mpared to those treated with ranitidine alone. Only scattered erosions were observed in antioxidant pre-treated group, but acid suppression by ranitid ine was not so effective in decreasing the severity of reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), increased NF-kapp aB activations, and depletions of reduced glutathione (GSH) were observed i n experimentally induced reflux esophagitis, but DA-9601 pre-treatment atte nuated the decrement of mucosal GSH levels and decreased MDA formations sig nificantly. DA-9601 treatment showed significant reductions in the activati on of NF-kappaB transcription factor. DA-9601 significantly decreased the p roliferating cell nuclear antigen-labeling index (PCNA-LI) of esophagus (P < 0.05) in chronic reflux esophagitis model and prevented the development o f Barrett's esophagus. In conclusion. reflux esophagitis provoked considera ble levels of oxidative stress in the esophageal mucosa. Antioxidant treatm ent seems to be the first line therapeutics in the prevention or treatment of reflux esophagitis. Moreover, antioxidant possibly played the chemopreve ntive role through preventing the development of Barrett's esophagus. (C) 2 001 Elsevier Science B.V. All rights reserved.