Article
Oxidative stress is more important than acid in the pathogenesis
of reflux oesophagitis in rats
T Y Ohb, J S Leec, B O Ahnb, H Chob, W B Kimb, Y B Kima, Y J Surhc, S W Choa, K M Leea, K B Hahma
a Department of
Pathology and Gastroenterology, Ajou University School of Medicine,
Suwon, Korea 442-749, b Dong-A Pharmaceutical Research
Institute, Yongin, Kyunggi-do, Korea, c College of
Pharmacy, Seoul National University, Seoul, Korea
Correspondence to: Dr K B Hahm, Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea 442-749. hahmkb{at}hotmail.com
Accepted for publication 29 March 2001
BACKGROUND
Although
antisecretory medications such as histamine type II receptor
antagonists or proton pump inhibitors have been used to treat reflux
oesophagitis, a considerable number of patients do not achieve complete
mucosal healing or suffer from either sustained symptoms or ensuing
complications, suggesting other damaging factors or impaired mucosal
resistance are also involved in the pathogenesis of reflux oesophagitis.
AIMS
The present study
was designed to evaluate oxidative stress as the major pathogenic
factor of reflux oesophagitis and to determine the usefulness of
antioxidants in the treatment of reflux oesophagitis.
MATERIALS AND
METHODS
Reflux oesophagitis was induced by
insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the
ligament of Treitz, in Sprague-Dawley rats.
RESULTS
DA-9601, a
novel antioxidant substance, significantly attenuated the gross and
histopathological scores of reflux oesophagitis compared with those
treated with ranitidine alone or reflux oesophagitis controls in a dose
dependent manner. Only scattered erosions were observed in the
antioxidant pretreated group but acid suppression by ranitidine was not
effective in decreasing the severity of reflux oesophagitis.
Significantly increased amounts of malondialdehyde (MDA), increased
nuclear factor
B (NF
B) activation, and depletion of reduced
glutathione (GSH) were observed in experimentally induced reflux
oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal
GSH levels and decreased MDA formation significantly. DA-9601 treatment
caused significant reductions in activation of NF
B transcription
factor, especially the p50 subunit, in accordance with the
significantly higher levels of inhibitory protein of NF
B expression.
CONCLUSION
Reflux
oesophagitis caused considerable levels of oxidative stress in the
oesophageal mucosa and antioxidant treatment should be considered as
supplementary therapy in the prevention or treatment of reflux
oesophagitis with acid suppression.
Keywords: reflux oesophagitis; antioxidants; oxidative stress; rat
© 2001 by Gut
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