ABSTRACT: BACKGROUND:Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. METHODS:We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. RESULTS:EP exerted significant antiplatelet actions: i) Impedance aggregometry amplitudes (11.7 ± 3.0 ohm, 0 ?g/mL EP) dose dependently decreased (7.8 ± 3.1 ohm, 1000 ?g/mL EP; -33.3%). ATP exocytosis (0.87 ± 0.24 nM, 0 ?g/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 ± 0.14 nM, 1000 ?g/mL; -35.6%). ii) Closure times (104.4 ± 23.8 s, 0 ?g/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 ± 82.5 s, 1000 ?g/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 ± 5.1%, 0 ?g/mL EP) dose-dependently decreased (9.0 ± 3.7%, 1000 ?g/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 ± 37.8, 0 ?g/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 ± 57.7 s, 1000 ?g/mL EP; +19.6%). Activated partial thromboplastin times (31.5 ± 1.8 s, 0 ?g/mL EP) were dose-dependently prolonged (35.6 ± 2.3 s, 1000 ?g/mL EP; +13.0%). Prothrombin times (0.94 ± 0.02 INR, 0 ?g/mL EP) were dose-dependently prolonged (1.09 ± 0.04 INR, 1000 ?g/mL EP; +16.0%). CONCLUSION:We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.
