QUINOLINIC ACID DOES NOT INFLUENCE COAGULATION PROFILE, NOR FIBRINOLYTIC ACTIVITY, UNDER PHYSIOLOGICAL CONDITIONS IN RATS.
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Disturbances of hemostatic system are commonly observed in chronic kidney disease (CKD) patients. Along with CKD progression, the levels of tryptophan-derived uremic toxins increase, including quinolinic acid (QA). Objective of the study was to evaluate the effect of QA, a representative of tryptophan metabolites, on coagulation and fibrinolytic activity in male Wistar rats in vivo and platelet activity in vitro. Rats received QA dissolved in drinking water in doses of 3, 10, and 30 mg/kg (or water, VEH) for 14 days. Next, the following parameters were measured in the rat‘s whole blood or plasma ex vivo: thromboelastometric (ROTEM) parameters, standard coagulation parameters and fibrinolytic parameters. To evaluate the direct effect of QA on coagulation and platelet activity, blood from control rats was drawn and analyzed in vitro in the following scheme: samples of whole blood were incubated with QA (100µM) before thromboelastometric (ROTEM) analysis and collagen-induced platelet aggregation, or samples of platelet rich plasma (PRP) were incubated with QA (100µM, 1 and 2mM) 10 minutes before collagen (1µg/ml) or ADP (10µM)-induced platelet aggregation. QA administrated for 14 days in drinking water had no effect per se on activation of coagulation and fibrinolytic parameters in rats ex vivo. Similarly, no changes were observed in a whole blood incubated directly with QA regarding coagulation parameters or collagen-induced platelet aggregation. QA inhibited ADP-induced platelets aggregation in PRP only at higher concentrations of 1 and 2 mM and when aggregation was initiated by the addition of 10µM ADP in vitro.
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