Hyeon Geun Cho

Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment

Abstract Background: The facts that the severity of reflux esophagitis cannot be accurately predicted on the basis of acid exposure and acid suppression treatment is not enough for the complete healing, suggested that other damaging factors might be involved in pathogenesis of reflux esophagitis. Aims: The present study was designed to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis and the importance of antioxidant in treatment of reflux esophagitis. Materials and Methods: Reflux esophagitis was induced by the insertion of small caliber ring (3 mm in diameter) into the duodenum 1 cm distal to the ligament of Treitz in rats. Results: DA-9601, a novel antioxidant substance, attenuated the gross esophagitis significantly compared to that treated with ranitidine, histamine-2 receptor antagonist (H2-RA), in a dose-dependent manner. Severe, hemorrhagic, and longitudinal ulcerations were developed in H2-RA pretreated group, whereas mildly scattered erosions were observed in antioxidant-pretreated group. Significantly increased amounts of malondialdehyde (MDA), increased NF-κB activation, and the mucosal depletion of reduced glutathione (GSH) were observed in the esophagus of reflux esophagitis. H2-RA treatment didn’t affect the levels of GSH and MDA, whereas DA-9601 attenuated the decrement of the GSH levels and significantly decreased lipid peroxides in the esophagus. Antioxidants treatment showed significant reductions in the activation of NF-κB, inflammation-associated transcription factor, especially p50 component in accordance with significant higher levels of NF-κB repressor, IκBα expression. Conclusion: Oxygen-derived free radicals seem to be one of the important mediators in generation of reflux esophagitis, which suggests that the combination of antioxidant and anti-secretory medications will be ideal and more beneficial in the prevention and treatment of reflux esophagitis than currently prescribed antisecretory treatment alone.

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 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 Barretts 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 Barretts 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 Barretts 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 Barretts esophagus.

S1087 The Prevalence and Predictive Factors for Silent Peptic Ulcer Disease in a Cohort of Unselected Patients Underwent Screening EGD

In patients with repetitive and troublesome belching an organic cause is seldom found and excessive air swallowing is considered the primary event. Previous study using combined impedance and pH monitoring (MII-pH) showed two patterns of retrograde gas flow through the esophagus, supragastric and gastric belching. The aim of our study was to investigate the incidence and pattern of belching during a 24 hrs period and to evaluate the effectiveness of chewing gum use in patients with belching by Rome III. Methods: Combined 24hrs MIIpH monitoring was performed in 12 patients (7 female; mean age: 46 yrs); in 6 of these patients with the distinct supragastric pattern of belching, a second MII-pH monitoring was performed, while the patients were ordered to chew a gum. Data presented as mean ± SEM. Results: During the study, the average rate of belching was 49.6 ± 14.7 per hour. The vast majority of belches (96%) were supragastric. Dividing the recording into 2 periods (daily and nocturnal), there was a significant difference between the daily and the nocturnal average rate (46.5 ± 14.1 vs. 1.9 ± 0.7, p<0.001). During monitoring with the use of chewing gum, a significant decrease in the rate of daily supragastric belches (11.3 ± 3.7 vs. 45.9 ± 13.7, p<0.001) was observed. None of the patients showed pathological acid reflux (% of time with pH<4: 2.9±0.5) and none of the supragastric belches was associated with acid or nonacid reflux events. Conclusions: Supragastric belches were the predominant belch pattern in patients with belching by Rome III. They mainly occurred in the daily upright position underlying the importance of psychological factors. The use of chewing gum, as a putative distracting mechanism, decreased the incidence of supragastric belches and seems to be effective in these patients.