Antithrombotic “in vivo” effects of quercetin 3,7,3’,4’-tetrasulfate isolated from Flaveria bidentis in an experimental thrombosis model in mice

Abstract

Quercetin 3, 7,3´4´-tetra-sulphate (QTS) has been shown to inhibit ?in vitro? platelet aggregation and to possess important anticoagulant and profibrinolytic effects. In this study, we examined the ?in vivo? antithrombotic activity of QTS in an experimental model of thrombosis in mice by using a test for acute pulmonary thromboembolism (APT). 80 male mice C57BL6 were used and randomly divided into 3 groups, control (n=30), treatment group (n=10 each concentration) and positive control (n=10). APT was induced by intravenous injection of a mixture of collagen and epinephrine after the treatment with QTS at four different concentrations. Paralyzed and dead mice of each group were registered and the percentage of protection against APT was calculated. In addition, the tail-bleeding assay and blood loss were determined under presence and absence of QTS at 100, 50, 25, and 10 mg/kg and were compared with data from mice administered with acetyl-salicylic acid (ASA). The histological examination of lung tissues showed the percentage of vessels that remained opened and those that were occluded by micro thrombi. QTS (100, 50, 25 and 10 mg/kg) administered i.p to mice showed antithrombotic activity preventing paralysis or death (90%, 90%, 70% and 20%, respectively) when a subsequent APT was induced. ASA 50 mg/kg was able to protect 70% of the positive control cases. Tail-bleeding time and blood loss were calculated and a dose-dependent profile of response was determined for QTS. Its activity was confirmed by a histologic examination of the lungs, in which the density of permeable blood vessels was significantly lower (92%, 88%, 77% and 31%, respectively; p <0.01) than in the mice untreated (negative control). We consider that QTS could be an interesting natural compound for treatment of thrombotic diseases. Further studies would be necessary to provide insights about the relevance of this compound and its clinical usefulness.