NO-aspirin: Mechanism of action and gastrointestinal safety

Digestive and Liver Disease

Volumn 35, Issue SUPPL. 2, 2003, Pages

  Fiorucci, S ^a   Del Soldato, P ^b,c  

^a UNIVERSITY OF PERUGIA   (Italy)

^b NicOx SA   (France)

^c NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

Anti inflammatory activity; Anti thrombotic activity; Nitric oxide releasing aspirins

Indexed keywords

ACETYLSALICYLIC ACID; ACETYLSALICYLIC ACID 3 (NITROXYMETHYL)PHENYL ESTER; ARACHIDONIC ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA CONVERTING ENZYME; ISOSORBIDE DINITRATE; ISOSORBIDE MONONITRATE; N ACETYL S NITROSOPENICILLAMINE; NITRIC OXIDE DONOR; PLACEBO; THROMBIN; DRUG DERIVATIVE; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT;

ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; DRUG TOLERABILITY; DUODENUM ULCER; GASTROINTESTINAL DISEASE; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; HUMAN; LOW DRUG DOSE; META ANALYSIS; NONHUMAN; STOMACH INJURY; STOMACH ULCER; STRUCTURE ACTIVITY RELATION; SYSTEMATIC REVIEW; THROMBOCYTE AGGREGATION INHIBITION; BLOOD FLOW; DIGESTIVE SYSTEM; DRUG EFFECT; THROMBOCYTE; THROMBOCYTE AGGREGATION; VASCULARIZATION;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ASPIRIN; BLOOD PLATELETS; DIGESTIVE SYSTEM; HUMANS; NITRIC OXIDE; PLATELET AGGREGATION; REGIONAL BLOOD FLOW;

EID: 1942544570     PISSN: 15908658     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1590-8658(03)00047-1     Document Type: Article

References (61)

1. Patrono C. Aspirin as an antiplatelet drug. New Engl J Med 1994;330:1287-94.
2. Fiorucci S, Antonelli E. Cyclo-oxygenase isoenzymes. Structural basis for selective inhibition of cyclo-oxygenases by anti-inflammatory agents. Dig Liver Dis 2001;33:S2-7.
3. Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci USA 1975;72:3073-6.
4. Awtry EH, Loscalzo J. Aspirin. Circulation 2000;101:1206-18.
5. Serhan CN, Oliw E. Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways. J Clin Invest 2001;107:1481-9.
6. Lee M, Cryer B, Feldman M. Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury. Ann Intern Med 1994;120:184-9.
7. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002;136:161-72.
8. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J 1988;296:313-6.
9. Medical Research Council's General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998;351:233-41.
10. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. HOT Study Group. Lancet 1998;351:1755-62.
11. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised in general practice. Lancet 2001;357:89-95.
12. Antiplatelet Trialist's Collaboration. Collaborative overview of randomized trials of antiplatelet therapy. I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81-106.
13. USPSTF. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med 2002;136:157-60.
14. Lanas A, Bajador E, Serrano P, Fuentes J, Carreno S, Guardia J, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal anti-inflammatory drugs, and the risk of upper gastrointestinal bleeding. New Engl J Med 2000;343:834-9.
15. Wallace JL. Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 1997;112:1000-16.
16. Wallace JL, Reuter B, Cicala C, McKnight W, Grisham MB, Cirino G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology 1994;107:173-9.
17. Wallace JL, Reuter B, Cicala C, McKnight W, Grisham MB, Cirino G. A diclofenac derivative without ulcerogenic properties. Eur J Pharmacol 1994;23:249-55.
18. Wallace JL, Elliott SN, Del Soldato P, McKnight W, Sannicolo F, Cirino G. Gastrointestinal sparing anti-inflammatory drugs: The development of nitric oxide-releasing NSAIDs. Drug Dev Res 1997;42:144-9.
19. MacNaughton WK, Cirino G, Wallace JL. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Sci 1989;45:1869-76.
20. Wallace JL, Miller MJS. Nitric oxide and mucosal defence: a little goes a long way. Gastroenterology 2000;119:512-20.
21. Wallace JL, McKnight W, Del Soldato P, Baydoun AR, Cirino G. Anti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative. J Clin Invest 1995;96:2711-8.
22. Wallace JL, Muscara MN, McKnight W, Dicay M, Del Soldato P, Cirino G. In vivo antithrombotic effects of a nitric oxide-releasing aspirin derivative, NCX-4016. Thromb Res 1999;93:43-50.
23. Fiorucci S, Santucci L, Antonelli E, Distrutti E, Del Sero G, Morelli O et al. NO-aspirin protects from T cell-mediated liver injury by inhibiting caspase-dependent processing of Th1-like cytokines. Gastroenterology 2000;118:404-21.
24. Fiorucci S, Antonelli E, Santucci L, Morelli O, Miglietti M, Federici B, et al. Gastrointestinal safety of nitric oxide-derived aspirin is related to inhibition of ICE-like cysteine proteases in rats. Gastroenterology 1999;116:1089-106.
25. Wallace JL, Ignarro LJ, Fiorucci S. Potential cardioprotective actions of NO-releasing aspirin. Nature Rev Drug Discov 2002;1:375-82.
26. Carini M, Aldini G, Stefani R, Orioli M, Facino RM. Nitrosylhemoglobin, an unequivocal index of nitric oxide release from nitroaspirin: in vitro and in vivo studies in the rat by ESR spectroscopy. J Pharm Biomed Anal 2001;26:509-18.
27. Fiorucci S, Mencarelli A, Mannucci R, Distrutti E, Morelli A, Del Soldato P, Moncada S. NCX-4016, a nitric oxide-releasing aspirin, chondrial function. FASEB J 2002;16:645-7.
28. Fiorucci S, Santucci L, Mencarelli A, Del Soldato P, Morelli A. Gastrointestinal safety of a NO-releasing aspirin derivative (NCX-4016) in humans: a double blind placebo-controlled endoscopic study. Gastroenterology 2003;124:600-7.
29. Minuz P, Lechi C, Tommasoli R, Gaino S, Degan M, Zuliani V, et al. Antiaggregating and vasodilatory effects of a new nitroderivative of acetylsalicylic acid. Thromb Res 1995;80:367-76.
30. Fiorucci S, Antonelli E, Burgaud JL, Morelli A. NO-releasing NSAIDs a review of their current status. Drugs Safety 2001;24:801-11.
31. Mezzasoma AM, Momi S, Guglielmini G, Leone M, Del Soldato P, Gresele P. Characterization of the activity of N.C.X. 4016, a nitric-oxide-releasing derivative of aspirin, on human blood platelets in vitro. Thromb Haemost 1999;79 Suppl:A230.
32. Lechi C, Andrioli G, Gaino S, Tommasoli R, Zuliani V, Ortolani R, et al. The antiplatelet effects of a new nitroderivative of acetylsalicylic acid, an in vitro study of inhibition on the early phase of platelet activation and on TxA2 production. Thromb Haemost 1996;76:791-8.
33. Minuz P, Degan M, Gaino S, Meneguzzi A, Zuliani V, Santonastaso CL, et al. NCX 4016 (NO aspirin) has multiple inhibitory effects in LPS-stimulated human monocytes. Br J Pharmacol 2001;134:905-11.
34. Fiorucci S, Mencarelli A, Meneguzzi A, Lechi A, Morelli A, Del Soldato P, Minuz P. NCX 4016 (NO-aspirin) inhibits LPS-induced factor expression in vivo: role of nitric oxide. Circulation 2002;106:3120-5.
35. Stamler JS, Lamas S, Fang FC. Nitrosylation. the prototypic redox-based signaling mechanism. Cell 2001;106:675-83.
36. Reed JC. Apoptosis-based therapies. Nature Rev Drug Discov 2002;1:111-21.
37. Dinarello CA, Margolis NH. Stopping the cuts: the recently discovered enzymes that process the precursors of inflammatory cytokines are good targets for the design of new anti-inflammatory therapeutic agents. Curr Biol 1995;5:587-90.
38. Thonberry N, Lazebnick Y. Caspases: enemies within. Science 1998;281:1312-6.
39. Sims JE. IL-1 and IL-18 receptors, and their extended family. Curr Opin Immunol 2002;14:117-22.
40. Fiorucci S. NO-releasing NSAIDs are caspase inhibitors. Trends Immunol 2001;22:232-5.
41. Fiorucci S, Santucci L, Cirino G, Mencarelli A, Familiari L, Soldato PD, et al. IL-1β converting enzyme is a target for nitric oxide-releasing aspirin: new insights in the antiinflammatory mechanism nitric oxide-releasing, nonsteroidal antiinflammatory drugs. J Immunol 2000;165:5245-54.
42. Fiorucci S, Santucci L, Antonelli E, Distrutti E, Del Sero G, Morelli O, et al. NO-aspirin protects from T-cell mediated liver injury by inhibiting caspase-dependent processing of Th1-like cytokines. Gastroenterology 2000;118:404-21.
43. Fiorucci S, Santucci L, Federici B, Antonelli E, Distrutti E, Morelli O, et al. Nitric oxide-releasing NSAIDs inhibit interleukin-1β converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFα. Aliment Pharmacol Ther 1999;13:421-35.
44. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nature Rev Mol Cell Biol 2002;3:214-20.
45. Pieper GM, Siebeneich W, Olds CL, Felix CC, Soldato PD. Vascular protective actions of a nitric oxide aspirin analog in both in vitro and in vivo models of diabetes mellitus. Free Radic Biol Med 2002;32:1143-56.
46. Kelley EE, Wagner BA, Buettner GR, Burns CP. Nitric oxide inhibits iron-induced lipid peroxidation in HL-60 cells. Arch Biochem Biophys 1999;370:97-104.
47. Weber C, Erl W, Pietsch A, Weber PC. Aspirin inhibits nuclear factor-κB mobilization and monocyte adhesion in stimulated human endothelial cells. Circulation 1995;91:1914-7.
48. Minto M, Del Soldato P, Ghezzi P, Fratelli M. A novel acetylsalicylic acid nitroderivative inhibits NF-κB activation and is antiproliferative to L929 cells (abstract). Inflamm Res 1997;46:S253.
49. Momi S, Emerson M, Paul W, Leone M, Mezzasoma AM, Del Soldato P, et al. Prevention of pulmonary thromboembolism by NCX 4016, a nitric oxide-releasing aspirin. Eur J Pharmacol 2000;397:177-85.
50. Muscara MN, Lovren F, McKnight W, Dicay M, Del Soldato P, Triggle CR, et al. Vasorelaxant effects of a nitric oxide-releasing aspirin derivative in normotensive and hypertensive rats. Br J Pharmacol 2001;133:1314-22.
51. Yamamoto T, Kakar NR, Vina ER, Johnson PE, Bing RJ. The effect of aspirin and two nitric oxide donors on the infarcted heart in situ. Life Sci 2000;67:839-46.
52. Wallace JL, McKnight W, Wilson TL, Del Soldato P, Cirino G. Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils. Am J Physiol 1997;273:G1246-51.
53. Muscará MN, Lovren F, McKnight W, Triggle CR, Cirino G, Wallace JL. Anti-hypertensive properties of a nitric oxide-releasing naproxen derivative in 2-kidney, 1-clip rats. Am J Physiol 2000;279:H528-35.
54. Muscará MN, McKnight W, Wallace JL. Effect of a nitric oxide-releasing naproxen derivative on hypertension and gastric damage induced by chronic nitric oxide inhibition in the rat. Life Sci 1998;62:235-40.
55. Napoli C, Cirino G, Del Soldato P, Sorrentino R, Sica V, Condorelli M, et al. Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice. Proc Natl Acad Sci USA 2001;98:2860-4.
56. Napoli C, Aldini G, Wallace JL, de Nigris F, Maffei R, Abete P, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis. Proc Natl Acad Sci USA 2002;99:1689-94.
57. Napoli C, Ackah E, Nigris Fd F, Soldato PD, D'Armiento FP, Crimi E, et al. Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice. Proc Natl Acad Sci USA 2002;99:12467-70.
58. Rossoni G, Berti M, De Gennaro Colonna V, Del Soldato P, Berti F. Myocardial protection by the nitroderivative of aspirin, NCX 4016: in vitro and in vivo experiments in the rabbit. Ital Heart J 2000;1:146-55.
59. Rossoni G, Manfredi B, de Gennaro Colonna V, Bernareggi M, Berti F. The nitroderivative of aspirin, NCX 4016, reduces infarct size caused by myocardial ischemia-reperfusion in the anesthetized rat. J Pharmacol Exp Ther 2001;297:380-7.
60. Armstead VE, Minchenko AG, Schuhl RA, Hayward R, Nossuli TO, Lefer AM. Regulation of P-selectin expression in human endothelial cells by nitric oxide. Am J Physiol 1997;273:H740-6.
61. Gresele P, Momi S, Mezzasoma AM. NCX 4016: a novel antithrombotic agent. Dig Liver Dis 2003;35(Suppl 2):S20-6.