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Protective effects of triflusal on secondary thrombus growth and vascular cyclooxygenase‐2
Author(s) -
DURAN X.,
SÁNCHEZ S.,
VILAHUR G.,
BADIMON L.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03036.x
Subject(s) - thrombus , cyclooxygenase , pharmacology , medicine , chemistry , biochemistry , enzyme
Summary. Background: Carotid residual mural thrombus predisposes to recurrent thrombosis and/or distal embolization (i.e. cerebrovascular ischemia). Objectives: Our aims were (i) to analyze and compare the efficacy of aspirin, triflusal, and its main metabolite 2‐hydroxy‐4‐trifluorometylbenzoic acid (HTB) on secondary thrombus growth; and (ii) evaluate to what extent the three Cox‐1 inhibitors influenced vascular Cox‐1/Cox‐2 expression and endothelial prostacyclin synthesis. Methods: In a rabbit model of ex vivo thrombosis, a fresh mural thrombus was formed on damaged vessels at flow conditions typical of mild and severe carotid stenoses. The effects of Cox‐1 inhibitors administered both intravenously (i.v.) (aspirin 5 mg kg −1 , triflusal 10 mg kg −1 , and HTB 10 mg kg −1 ) and orally (p.o.) (8 days; aspirin 30 mg kg −1 day −1 , and triflusal 40 mg kg −1 day −1 ) on secondary thrombus growth were assessed by In‐ 111 deposited platelets and compared with a placebo control. Arterial Cox‐1/Cox‐2 expression after 8‐day treatment was evaluated at mRNA and protein levels. Additionally, a drug‐related dose‐dependent in vitro assay was performed for endothelial PGI 2 release measurement (Cox‐2 activity). Results: All Cox inhibitors similarly and significantly ( P < 0.05) reduced secondary thrombus formation after i.v. and p.o. administration versus placebo control. Treatments exerted no effect on vascular Cox‐1 mRNA whereas Cox‐2 mRNA was moderately reduced by aspirin and triflusal (placebo 100% ± 9%, aspirin 70% ± 2% and triflusal 70% ± 2%; P < 0.05). Cox‐2 protein levels were slightly higher in the triflusal versus aspirin group (placebo 100% ± 6%, aspirin 35% ± 10% and triflusal 61% ± 9%; P < 0.005 versus placebo). Interestingly, in vitro , HTB solely maintained endothelial PGI 2 synthesis levels similar to the control. Conclusions: At a similar level of efficacy in inhibiting secondary thrombosis, triflusal seems to better preserve Cox‐2 expression than aspirin and its metabolite HTB was able to protect endothelial prostacyclin production.