D-003, a potential antithrombotic compound isolated from sugar cane wax with effects on arachidonic acid metabolites

D-003 is a natural mixture of higher primary saturated aliphatic acids purified from sugar cane wax, whose main component is octacosanoic acid followed by triacontanoic, dotriacontanoic, and tetratriacontanoic acids. D-003 inhibits platelet aggregation and arterial thrombosis experimentally induced in a dose-dependent fashion. This study was undertaken to investigate the effects of D-003 (25 and 200 mg/kg) in experimental models of venous thrombosis and on plasma levels of two metabolites from arachidonic acid (AA) : thromboxane A(2) (TxA(2)) and prostacyclin (PgI(2)). D-003 orally administered as single doses of 200 mg/kg, but not at 25 mg/kg, significantly increased plasma levels of 6 keto PgF1alpha levels, a stable metabolite of PgI(2) in PPP obtained from collagen-stimulated blood (4 microg/ml) compared with control group. Nevertheless, levels of 6 keto PgF1alpha levels determined after 10 days of oral treatment with both doses of D-003 were significantly larger than those of the controls. Likewise, single and repeated oral doses of D-003 (25 and 200 g/kg) significantly reduced the TxB(2) and MDA plasma levels obtained from whole blood stimulated by collagen. Hence, TxB(2)/6 keto PgF1alpha ratio significantly decreased in animals treated with D-003. Single and repeated oral doses of D-003 (25 and 200 mg/kg) significantly reduced the weight of venous thrombus experimentally induced in rats. D-003 at single doses (400 mg/kg but not 200 mg/kg) significantly protected from death induced by endovenous infusion of collagen plus epinephrine in mice. The present results support that these effects of D-003 on AA metabolites could explain, at least partially, its antiplatelet and antithrombotic effects.