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| Content Provider | PubMed Central |
|---|---|
| Author | Fiorucci, Stefano Santucci, Luca Wallace, John L. Sardina, Marco Romano, Mario Del, Soldato Piero 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 ≈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. |
| Related Links | http://dx.doi.org/10.1073/pnas.1933204100 |
| Ending Page | 10941 |
| Page Count | 5 |
| Starting Page | 10937 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 100 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2003-09-16 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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