Interaction of a selective cyclooxygenase-2 inhibitor with aspirin and NO-releasing aspirin in the human gastric mucosa.

Content Provider	Semantic Scholar
Author	Fiorucci, Stefano Santucci, Luca Wallace, John L. Sardina, Marco Romano, Mário Soldato, Piero Del Morelli, Antonio
Copyright Year	2003
Abstract	In addition to inhibiting cyclooxygenase (COX)-1-derived prostanoid biosynthesis, aspirin acetylates COX-2, enabling the conversion of arachidonic acid to 15(R)-epi lipoxin A4, or aspirin-triggered lipoxin (ATL). Selective COX-2 inhibitors block ATL formation and exacerbate mucosal injury in rats treated with aspirin. In the present study, we have examined whether inhibition of COX-2 activity in healthy volunteers taking aspirin exacerbates gastric mucosal injury and if such an effect would be prevented by NCX-4016, a NO-releasing derivative of aspirin. Thirty-two volunteers were randomized to receive 2 wk of treatment with NCX-4016 (800 mg twice a day) or aspirin (100 mg once a day) alone or in combination with 200 mg of celecoxib twice a day. Mucosal damage was assessed by endoscopy. The mean mucosal injury score was 5.8 +/- 1.8 in subjects treated with aspirin and 2.4 +/- 0.7 (P < 0.01 vs. aspirin) in subjects treated with NCX-4016. Administration of celecoxib increased the injury score in volunteers treated with aspirin (9.9 +/- 1.9) but not in subjects taking NCX-4016 (1.5 +/- 0.8). Aspirin and NCX-4016 caused a comparable suppression of serum thromboxane B2 levels and increased urinary excretion of ATL. Celecoxib inhibited endotoxin-induced prostaglandin E2 generation in whole blood by approximately 80% and abolished ATL formation. These findings suggests that (i) aspirin and NCX-4016 trigger ATL formation in humans, (ii) celecoxib inhibits ATL formation and exacerbates the mucosal injury caused by low doses of aspirin, and (iii) the NO-donating moiety of NCX-4016 protects the gastric mucosa even in the presence of suppression of COX-1 and COX-2.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.pnas.org/content/100/19/10937.full.pdf
PubMed reference number	12960371v1
Volume Number	100
Issue Number	19
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Subject Keyword	Anabolism Arachidonic Acid Aspirin Cyclooxygenase 2 Inhibitors Dinoprostone Eighty Gastric mucosa Inhibition Lipoxins Mallory-Weiss Syndrome Mucous Membrane NCX 4016 Prostaglandin-Endoperoxide Synthase Prostaglandins Thromboxane B2 Thromboxanes celecoxib prostanoid biosynthetic process
Content Type	Text
Resource Type	Article