Anticoagulant, anti-aggregation and antithrombotic effects of a novel hexapeptide

Abstract

Hexapeptide is a novel synthetic oligopeptide with a structure similar to that of eptifibatide. This study was designed to investigate the anticoagulant, anti-aggregation, disaggregation and anti-thrombogenesis effects of hexapeptide. The effects of antiplatelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin, and the effect of disaggregation of platelet aggregation induced by ADP were determined. The anticoagulation indexes were determined by different kits. Hexapeptide 1 × 10(-5) -1 × 10(-4) m could significantly prolong rabbit blood clotting time, thrombin time, prothrombin time and activated partial thromboplastin enzyme time, and reduce the length, wet weight, dry weight and the index of thrombus in a concentration-dependent manner. Hexapeptide 1 × 10(-4) m decreased platelet adhesion rate by 40.2%. The platelet aggregation inhibition of hexapeptide in dogs and humans was more obvious than in rabbits and rats. The aggregation inhibition rate of 1 × 10(-5) m hexapeptide in dogs, rabbits, rats and humans induced by ADP was 93.9 ± 1.3%, 66.2 ± 1.4%, 76.1 ± 3.2% and 99.8 ± 0.2%, respectively; the 50% inhibitory concentration (IC50) of hexapeptide was 7.24 × 10(-8), 3.24 × 10(-6), 6.61 × 10(-6) and 8.91 × 10(-8) m, respectively. For the aggregation inhibition rate of hexapeptide in dogs, rabbits and humans induced by AA, the IC50 was 1.29 × 10(-9), 1.32 × 10(-6) and 9.33 × 10(-8) m, respectively; the IC50 of aggregation inhibition rates induced by thrombin was 2.88 × 10(-6), >1 × 10(-5) and 4.17 × 10(-6) m, respectively. The disaggregation rate of 1 × 10(-4) m hexapeptide in dog induced by ADP was 68.8 ± 7.4%. Hexapeptide has anticoagulant, antiplatelet aggregation, disaggregation and antithrombotic effects in vitro.