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The effect of single‐dose naproxen on eicosanoid formation in human gastroduodenal mucosa
Author(s) -
TREIBER G.,
WEX T.,
LINK A.,
VIETH M.,
LAUFER S.,
MALFERTHEINER P.
Publication year - 2006
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2006.02725.x
Subject(s) - medicine , naproxen , aspirin , gastric mucosa , eicosanoid , thromboxane , prostacyclin , leukotriene b4 , prostaglandin , prostaglandin e , helicobacter pylori , gastroenterology , thromboxane b2 , pharmacology , endocrinology , stomach , platelet , chemistry , inflammation , pathology , biochemistry , arachidonic acid , enzyme , alternative medicine
Summary Background In animal studies, aspirin and non‐aspirin non‐steroidal anti‐inflammatory drugs contribute to gastroduodenal damage via cyclo‐oxygenase inhibition and consecutive leucotriene formation (COX‐LOX eicosanoid shunt). Aim and methods Ten Helicobacter pylori ‐negative healthy volunteers received a single dose of 500 mg naproxen to address two questions: (i) is there a crosstalk between eicosanoids before medication in the human gastroduodenal mucosa and (ii) can we demonstrate a COX‐LOX shunt following single‐dose naproxen? Results Significant correlations in the stomach mucosa before medication were obtained between leucotriene B4 (LTB4) and thromboxane B 2 (TxB 2 ; r = −0.38, P = 0.05), as well as LTB4 and prostaglandin E 2 (PGE 2 ; r = 0.71, P < 0.0001). In serum, a >90% inhibition of TxB 2 and PGE 2 occurred within 30 min of naproxen administration. In gastric mucosa, a significant decrease of TxB 2 occurred already at 15 min and preferably in the antrum. For LTB4 there was a non‐significant trend towards a transient increase. Mucosal PGE 2 was unchanged in all regions; transcript levels of both cyclo‐oxygenases/5‐lipoxygenase were unaffected (except for a trend of increasing cyclo‐oxygenase‐2 in the corpus). Conclusions Baseline correlations between LTB4‐TxB 2 and LTB4‐PGE 2 reflect a crosstalk between these eicosanoids. A COX‐LOX shunt; however, cannot be demonstrated following single‐dose naproxen in a low‐risk population.