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.
Molina
V
V
Center of Natural Products, National Center for Scientific Research, Cubanacan, Havana, Cuba.
Arruzazabala
M L
ML
Carbajal
D
D
Más
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005227:Fatty Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D031786:Saccharum / Q000737:chemistry*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013929:Thromboxane B2 / Q000097:blood; D020246:Venous Thrombosis / Q000188:drug therapy / Q000473:pathology; D014885:Waxes / Q000737:chemistry*
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D005343:Fibrinolytic Agents; D014885:Waxes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D004837:Epinephrine