Effects of copper-aspirin complex on platelet aggregation and thrombosis in rabbits and mice.
The effects of intragastric and intraduodenal copper-aspirin complex on rabbit platelet aggregation were observed by Born's method. Myers's method was used to evaluate the antithrombotic effect of copper-aspirin complex in mice. In-vitro copper-aspirin complex selectively inhibited arachidonic acid-induced platelet aggregation with an IC50 value (concentration resulting in 50% inhibition) of 13.2 microM (95% confidence limits 9.1-16.8 microM). Copper-aspirin complex (10 mg kg(-1) given intragastrically or intraduodenally) was more potent than aspirin in inhibiting arachidonic acid-induced platelet aggregation. Copper-aspirin complex (10 mg kg(-1)) had a stronger inhibitory effect and a longer duration of action when given intragastrically than when given intraduodenally. It was shown by radioimmunoassay that copper-aspirin complex significantly reduced the level of thromboxane B2 in plasma while markedly increasing that of 6-ketoprostaglandin F1alpha (6keto-PGF1alpha). Copper-aspirin complex (10 mg kg(-1) given intragastrically for 7 days) significantly reduced mouse mortality caused by intravenous injection of arachidonic acid. The results suggest that both in-vitro and in-vivo copper-aspirin complex is more potent in selectively inhibiting arachidonic acid-induced platelet aggregation than aspirin. When given intragastrically the complex has a more potent antiplatelet effect and a longer duration of action than when given intraduodenally. The antithrombotic effect of the complex was more potent than that of aspirin.
Shen
Z Q
ZQ
Yunnan Pharmacological Laboratories of Natural Products, Kunming Medical College, China.
Liang
Y
Y
Chen
Z H
ZH
Liu
W P
WP
Duan
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D066298:In Vitro Techniques; D007441:Intubation, Gastrointestinal; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D011897:Random Allocation; D013927:Thrombosis / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000097:blood
D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003300:Copper; D001241:Aspirin