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 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.


OBJECTIVE
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.


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-kappaB 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-kappaB, inflammation-associated transcription factor, especially p50 component in accordance with significant higher levels of NF-kappaB repressor, IkappaBalpha expression.


CONCLUSIONS
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.
Oh
T Y
TY
Dong-A Pharmaceutical Research Institute, Yongin, Kyunggi-do, South Korea.
Lee
J S
JS
Ahn
B O
BO
Cho
H
H
Kim
W B
WB
Kim
Y B
YB
Surh
Y J
YJ
Cho
S W
SW
Hahm
K B
KB
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004942:Esophagitis, Peptic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D005744:Gastric Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020672:I-kappa B Proteins; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects; D004364:Pharmaceutical Preparations; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D000975:Antioxidants; C116959:DA 9601; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007527:Isoenzymes; D008054:Lipid Peroxides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D004364:Pharmaceutical Preparations; D010936:Plant Extracts; D000072000:NF-KappaB Inhibitor alpha; D008315:Malondialdehyde; D011899:Ranitidine; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005978:Glutathione