Antiplatelet and Antithrombotic Effect of D-003

Abstract

D-003 is a mixture of higher primary aliphatic saturated acids purified from sugar cane wax whose main component is octacosanoic acid followed by triacontanoic, dotriacontanoic, and tetratriacontanoic acids. The aim of this study was to evaluate the effects of D-003 on: ex vivo platelet aggregation, arterial thrombosis and bleeding time in rats. In addition, time course of antiplatelet effects of D-003 was also investigated on ex vivo platelet aggregation in guinea-pigs. D-003 (25–200 mg kg−1) orally administered at single or repeated doses (3 days) inhibited platelet aggregation induced by collagen (2.2 μ g ml−1) and ADP (2μ mol l−1) in rats, and collagen (0.25 μ g ml−1) induced aggregation in guinea-pigs in a dose-dependent manner. Single doses of D-003 (5–500 mg kg−1) administered orally 2 h before induction of arterial thrombosis significantly inhibited the reduction of rectal temperature. D-003 administered at a single dose (50–200 mg kg−1) 2 h before the experiment significantly increased the bleeding time in a dose-dependent manner. The time-course effects of D-003 on platelet aggregation, arterial thrombus formation, and bleeding time showed no effect 0.5 h after dosing, and maximal effects exhibited 1–2 h after treatment, whereas no significant effects were found 4 h after treatment.