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

Background: The facts that the severity of reflux esophagitis cannot be acc urately predicted on the basis of acid exposure and acid suppression treatm ent is not enough for the complete healing, suggested that other damaging f actors might be involved in pathogenesis of reflux esophagitis. Aims: The p resent study was designed to evaluate the oxidative stress as the major pat hogenic factor of reflux esophagitis and the importance of antioxidant in t reatment of reflux esophagitis. Materials and Methods: Reflux esophagitis w as induced by the insertion of small caliber ring (3 mm in diameter) into t he duodenum 1 cm distal to the ligament of Treitz in rats. Results: DA-9601 , a novel antioxidant substance, attenuated the gross esophagitis significa ntly compared to that treated with ranitidine, histamine-2 receptor antagon ist (H2-RA), in a dose-dependent manner. Severe, hemorrhagic, and longitudi nal ulcerations were developed in H2-RA pretreated group, whereas mildly sc attered erosions were observed in antioxidant-pretreated group. Significant ly increased amounts of malondialdehyde (MDA), increased NF-KB 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-KB, inflamm ation-associated transcription factor, especially p50 component in accordan ce with significant higher levels of NF-KB repressor, I kappaB alpha expres sion. Conclusion: Oxygen-derived free radicals seem to be one of the import ant 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. (C) 2001 Elsevier Scie nce Inc.