Effect of quinolinic acid – A uremic toxin from tryptophan metabolism – On hemostatic profile in rat and mouse thrombosis models

Abstract Purpose We aimed to determine the effect of quinolinic acid (QA) on hemostasis in rat and mouse models of thrombosis. Material and methods Wistar rats (male, n = 72) received QA dissolved in drinking water in doses of 3, 10, 30 mg/kg or pure drinking water (vehicle control group -VEH) for 14 days. On the 14 th day of the experiment the effect of QA on hemostasis was evaluated using electrically induced arterial thrombosis model. The following parameters were measured: thrombus weight, hematology, thromboelastometric (ROTEM) parameters, TXA 2 and 6-keto-PGF 1α concentration, coagulation and fibrinolytic markers activity and concentration. GFP mice (male, n = 30) were assigned to the group receiving QA (30 mg/kg) or VEH for 14 days and to the group receiving: single intravenous dose of QA (30 mg/kg) or VEH or the same dose of QA and anti-CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1) antibody conjugated with Alexa Fluor 647. The effect of QA on hemostasis was evaluated in the model of laser-induced injury of mesentery vein using intravital confocal microscopy. Results Administering QA for 14 days resulted in a divergent, depending on dose, increase in concentration of active form of tPA and PAI-1 and concentration of total PAI-1 and PAP complexes in rats’ plasma. In turn, administering QA for 14 days in mice revealed its prothrombotic activity, while single-dose IV administration revealed its antithrombotic activity, through the up-regulation of PECAM-1 expression. Conclusions We demonstrated the first evidence for the opposite biological effects of QA on hemostasis in rat and mouse thrombosis models.