Document Detail


Proton pump inhibitor therapy in gastro-oesophageal reflux disease decreases the oesophageal immune response but does not reduce the formation of DNA adducts.
MedLine Citation:
PMID:  18384663     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chronic oesophageal inflammation and related oxidative stress are important in the pathogenesis of erosive oesophagitis (EO) and its malignant progression. AIM: To study the effect of proton pump inhibitors (PPIs) on oesophageal cellular immune response and oxidative damage in EO patients. METHODS: Forty gastro-oesophageal reflux disease (GERD) patients [non-erosive reflux disease (NERD): 15, EO: 25] were included, after 7 days off antisuppressive drugs. EO patients were randomized to 20-mg rabeprazole once daily for either 4 or 8 weeks with baseline and follow-up endoscopy with distal oesophageal biopsies. T lymphocytes, macrophages and mast cells were quantified by immunohistochemistry. DNA adducts were measured by analysis of 8-oxo-deoxyguanosine levels. RESULTS: Erosive oesophagitis patients had more T lymphocytes and CD8(+) T lymphocytes in squamous epithelium than NERD patients (P = 0.001, P = 0.002, respectively). Levels of DNA adducts between both groups were, however, not different (P = 0.99). Four- and eight-week rabeprazole treatment in EO patients resulted in a significant decrease in number of T lymphocytes and CD8(+) T lymphocytes (all P < 0.05). PPIs did not, however, affect levels of DNA adducts. CONCLUSIONS: Short-term PPI therapy in EO patients reduces the oesophageal cellular immune response, but does not change oxidative damage. PPI therapy may therefore not be effective in reducing the risk of oesophageal cancer in GERD patients.
Authors:
P J F De Jonge; P D Siersema; S G J Van Breda; K P M Van Zoest; D J Bac; I Leeuwenburgh; R J Th Ouwendijk; H Van Dekken; J G Kusters; E J Kuipers
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-03-31
Journal Detail:
Title:  Alimentary pharmacology & therapeutics     Volume:  28     ISSN:  1365-2036     ISO Abbreviation:  Aliment. Pharmacol. Ther.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-05     Completed Date:  2008-12-10     Revised Date:  2009-01-24    
Medline Journal Info:
Nlm Unique ID:  8707234     Medline TA:  Aliment Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  127-36     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. p.dejonge@erasmusmc.nl
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD / immunology
Antigens, Differentiation, Myelomonocytic / immunology
Barrett Esophagus / immunology
DNA Adducts / drug effects*,  metabolism
Female
Gastroesophageal Reflux / drug therapy,  immunology*
Humans
Immunity, Cellular
Male
Mast Cells / immunology
Middle Aged
Oxidative Stress / genetics,  immunology
Proton Pump Inhibitors / therapeutic use*
T-Lymphocytes / immunology
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/DNA Adducts; 0/Proton Pump Inhibitors

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