Synergistic effect of D-003 and aspirin on experimental thrombosis models.
D-003 is a mixture of higher primary aliphatic saturated acids purified from sugarcane wax, with antiplatelet and antithrombotic effects experimentally demonstrated. Octacosanoic acid is the main component of D-003, followed by triacontanoic, dotriacontanoic, and tetracontanoic acids, while other acids are minor components. This work investigates the effects of combination therapy D-003+aspirin (ASA) on arachidonic acid (AA)-induced sudden death in mice and bleeding time in rats. In addition, the effects of D-003 on serum levels of two metabolites of AA: thromboxane A(2) and prostacyclin, assessed through the measurement of their stable metabolites: thromboxane B(2) (TxB(2)) and 6 keto PgF1alpha by radioimmunoassay kits, were also investigated. Combination therapy of D-003 (50mg/kg) and ASA (3mg/kg) significantly increased bleeding time in rats in a synergistic manner compared with D-003 or ASA alone. Moreover, the combined treatment of D-003 (200mg/kg) and ASA (5mg/kg) in mice protected against AA-induced sudden death (83% survivors) in a synergistic manner which was compared with each treatment alone (33% survivors). These results indicate that antiplatelet effects of D-003 are not mediated by a cyclooxygenase inhibition. D-003 and ASA monotherapies reduced serum TxB(2) levels, whereas D-003, but not ASA, significantly increased 6 keto PgF1alpha levels.
Molina
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Center of Natural Products, National Center for Scientific Research, Ave 25 and 158, Cubanacán, Havana 6880, Cuba. clinica@ip.etecsa.cu
Arruzazabala
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ML
Carbajal
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D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage; D001241:Aspirin / Q000627:therapeutic use*; D003645:Death, Sudden / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005227:Fatty Acids / Q000627:therapeutic use*; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000097:blood
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin