The effect of single-dose naproxen on eicosanoid formation in human gastroduodenal mucosa.
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).


OBJECTIVE
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.
Treiber
G
G
Department of Gastroenterology and Hepatology, University Hospital, Magdeburg, Germany. gerhard.treiber@medizin.uni-magdeburg.de
Wex
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T
Link
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Vieth
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Laufer
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Malfertheiner
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D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D011458:Prostaglandins E; D007975:Leukotriene B4; D013929:Thromboxane B2; D009288:Naproxen