NCX4016 (NO-Aspirin) has multiple inhibitory effects in LPS-stimulated human monocytes

British Journal of Pharmacology
P MinuzA Lechi

Abstract

NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A., France) is an anti-thrombotic agent, chemically related to acetylsalicylic acid (ASA) and able to release NO. We tested the effects of NCX4016 and ASA on the release of the thromboxane (TX) A(2) metabolite TXB(2), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), expression and activity of tissue factor (TF) in stimulated, adherent human monocytes. Both ASA and NCX4016 1 - 1000 micromol l(-1) dose-dependently reduced TXB(2) concentration, measured by RIA in the supernatant of 10 microg ml(-1) LPS-stimulated cells. NCX4016 activity was comparable to that of equimolar ASA when incubation lasted 6 h (NCX4016 30 micromol l(-1): -86.0+/-10.1%, NCX4016 300 micromol l(-1): -92.2+/-9.0%, ASA 30 micromol l(-1): -92.3+/-7.5%, ASA 300 micromol l(-1): -97.3+/-1.0%, n=6, M+/-s.d.). Most of the activity of NCX4016 up to 100 micromol l(-1) was prevented by 10 micromol l(-1) ODQ, inhibitor of cyclic GMP. NCX4016 100 - 300 micromol l(-1) reduced TNF-alpha (NCX4016 300 micromol l(-1)=-77.2+/-19.9%, n=6) and IL-6 (NCX4016 300 micromol l(-1): -61.9+/-15.2%, n=6) in LPS stimulated monocytes while ASA had no significant effects. TF activity (NCX4016 300 micromol ...Continue Reading

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Citations

Jan 16, 2007·Journal of Thrombosis and Thrombolysis·Luci Maria SantAna DusseBashir A Lwaleed
Jul 9, 2003·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·S Fiorucci, P Del Soldato
Jul 9, 2003·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·P GreseleA M Mezzasoma
Apr 11, 2003·Fundamental & Clinical Pharmacology·Stéphane Cook, Urs Scherrer
Jan 24, 2003·Annual Review of Pharmacology and Toxicology·Claudio Napoli, Louis J Ignarro
Dec 17, 2011·International Immunopharmacology·Muzammal HussainMuti Ur Rehman
Apr 3, 2007·British Journal of Pharmacology·M R Miller, I L Megson
Feb 1, 2005·European Journal of Pharmacology·Paula ZacharowskiJane Mitchell
Mar 3, 2007·Drug Metabolism and Pharmacokinetics·Yukiko MinamiyamaShigeru Okada
Dec 23, 2016·Medicinal Research Reviews·Catarina Pereira-LeiteSalette Reis
Nov 17, 2010·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Anastazia A KeiEvangelos N Liberopoulos
Nov 16, 2006·Expert Opinion on Therapeutic Targets·Catriona M TurnbullIan L Megson

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