Oxidative damage has long been related to mucosal damages of gastrointestinal tracts and their ensuing
carcinogenesis. In spite of treatment with anti-secretory medications for
reflux esophagitis, considerable portions of patient did not achieve the complete mucosal healings or suffered from sustaining 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 evaluate the oxidative stress as the major pathogenic factor of
reflux esophagitis or to find out the usefulness of
antioxidant in the treatment of
reflux esophagitis and the prevention of development of
Barrett's esophagus. Acute or chronic
reflux esophagitis was induced through either narrowing the third portion of duodenal lumen or performing
myotomy of lower esophageal sphincter in rats, respectively.
DA-9601, a new phytopharmaceutical possessing antioxidative properties, significantly attenuated the gross and histopathologic scores of acute
reflux esophagitis in a dose-dependent manner compared to those treated with
ranitidine alone. Only scattered erosions were observed in
antioxidant pre-treated group, but
acid suppression by
ranitidine was not so effective in decreasing the severity of
reflux esophagitis. Significantly increased amounts of
malondialdehyde (MDA), increased
NF-kappa B activations, and depletions of
reduced glutathione (GSH) were observed in experimentally induced
reflux esophagitis, but
DA-9601 pre-treatment attenuated the decrement of mucosal GSH levels and decreased MDA formations significantly.
DA-9601 treatment showed significant reductions in the activation of
NF-kappa B transcription factor.
DA-9601 significantly decreased the
proliferating cell nuclear antigen-labeling index (
PCNA-LI) of esophagus (P<0.05) in chronic
reflux esophagitis model and prevented the development of
Barrett's esophagus. In conclusion,
reflux esophagitis provoked considerable levels of oxidative stress in the esophageal mucosa.
Antioxidant treatment seems to be the first line
therapeutics in the prevention or treatment of
reflux esophagitis. Moreover,
antioxidant possibly played the chemopreventive role through preventing the development of
Barrett's esophagus.