This Article Abstract Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fiorucci, S. Articles by Minuz, P. Search for Related Content PubMed PubMed Citation Articles by Fiorucci, S. Articles by Minuz, P.

Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans

Stefano Fiorucci, MD^*, Andrea Mencarelli, BS^*, Alessandra Meneguzzi, BS, Alessandro Lechi, MD, Barbara Renga, BS^*, Piero del Soldato, PhD, Antonio Morelli, MD^* and Pietro Minuz, MD^,*

^* Clinica di Gastroenterologia ed Epatologia, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Section of Internal Medicine, Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy
NicOx S.A., Sophia Antipolis, France
New York Medical College, Valhalla, New York, USA

View larger version (32K): [in a new window]   Figure 1 Effect of NCX-4016 and aspirin (ASA) on gastric mucosa as evaluated by endoscopy after the administration of NCX-4016, ASA, or both drugs for 21 days (A). NCX-4016 administration was associated with less extended gastric damage, compared with aspirin alone, as assessed using a modified Lanza's score. Both aspirin and NCX-4016 reduced the content of prostaglandins E2 (PGE2) and F2 (PGF2) in the gastric mucosa (B). Means and standard errors, n = 12; *p < 0.001 vs. placebo; **p < 0.001 vs. ASA alone.

View larger version (27K): [in a new window]   Figure 2 Platelet aggregation induced by 0.6 mmol/l arachidonic acid was completely inhibited by prolonged administration of NCX-4016, aspirin (ASA), and NCX-4026 plus ASA (A). This was accompanied by a statistically significant reduction in the serum concentration of thromboxane (TX) B2, index of cyclooxygenase activity in platelets (B), and urinary excretion of 11-dehydro(dh)-TXB2, index of in vivo TXA2 biosynthesis (C). Means and standard errors, n = 12; *p < 0.0001 vs. placebo.

View larger version (35K): [in a new window]   Figure 3 Tissue factor (TF) expression in monocytes (CD14+ cells) was induced ex vivo by either 2 mmol/l thrombin receptor activator protein (TRAP) (A and B) or 10 mmol/l lipopolysaccharide (LPS) (C and D). The administration of NCX-4016 either alone or in combination with acetylsalicylic acid (ASA) reduced TF expression compared with placebo and ASA alone, as assessed by flow-cytometry and measuring the percentage of positive cells and fluorescence intensity (MIF). n = 12. *p < 0.05 LPS or TRAP vs. untreated cells; **p < 0.05 NCX-4016 vs. LPS or TRAP; p < 0.05 NCX-4016 and ASA vs. ASA alone.

View larger version (38K): [in a new window]   Figure 4 The administration of NCX-4016 either alone or in combination with aspirin (ASA) reduced the secretion of monocyte chemoattractant protein-1 (MCP-1) (A), interleukin-6 (IL-6) (B), and expression of CD11b (C and D) compared with placebo and ASA alone. n = 12. *p < 0.05 vs. placebo and ASA alone.