Platelet cyclooxygenase activity

A thrombotic tendency is present in diabetes due to an imbalance between prostacyclin and thromboxane. Lipid peroxides and newly generated free radicals are thought to inhibit the vasodilator and anti-platelet effects of endothelial-derived prostacyclin, but stimulate platelet cyclooxygenase activity, thereby promoting the production of thromboxane A2. This leads to vasoconstriction and platelet aggregation - the concept of peroxide vascular tone (Halliwell and Gutteridge, 1989). 

Aspirin has emerged as a very nsefnl antithrombotic agent because of its action against platelet cyclooxygenase activity. 

VITAMIN E AND PLATELET AGGREGATION a-Tocopherol, a natural antioxidant, inhibits platelet aggregation and release. The effect of vitamin E is dne to a redaction in platelet cyclooxygenase activity and inhibition of lipid peroxide formation. It is believed that snpplementing the diet with vitamin E could play a role in the treatment of thromboembolic disease, especially if it is given in conjnnc-tion with an inhibitor of platelet aggregation. 

Platelet Inhibition Ginger extract has been found to inhibit platelet aggregation induced by arachidonic acid, epinephrine, ADP, and collagen (Srivastava 1984). The extract s ability to inhibit cyclooxygenase activity and thromboxane levels correlated well with inhibition of platelet aggregation (Srivastava 1984 Mustafa et al. 1993). The type of preparation used also affects platelet inhibition, because roasted and charcoal of ginger were effective, while ether extracts of raw and dried ginger were not (Wu et al. 1993). 

The anti-inflammatory activity of the NSAIDs is mediated chiefly through inhibition of biosynthesis of prostaglandins (Figure 36-2). Various NSAIDs have additional possible mechanisms of action, including inhibition of chemotaxis, down-regulation of interleukin-1 production, decreased production of free radicals and superoxide, and interference with calcium-mediated intracellular events. Aspirin irreversibly acetylates and blocks platelet cyclooxygenase, while most non-COX-selective NSAIDs are reversible inhibitors. 

Platelet-poor plasma is prepared from venous blood by centrifugation at 1000 xg for 15 min, and an equal volume of ethanol is added. The mixture is left on ice for 10 min and then centrifuged at 6500 xg for 15 min. Cyclooxygenase activity is measured polarographically, using an oxygen electrode and an incubation buffer (total volume 3 ml) containing potassium phosphate (pH 7.2, 0.1 M), 100 pM arachidonic acid, 1 mM phenol and 2.5 mM sodium cyanide. The reaction is... 

These anthors concluded that addition of a NO-donating moiety to aspirin resnlts in a new chemical entity that maintains cyclooxygenase-1 and platelet inhibitory activity while nearly avoiding gastrointestinal damage. ... 

Human platelet thromboxane synthetase does not possess peroxidase activity, since the two hydroperoxides, 12-hydroperoxy-5,8,10-heptadecatrienoic acid and 15-hydroperoxy TXBj were detected in incubates from PGG, with partially purified thromboxane synthetase which was devoid of cyclooxygenase activity [36]. 

Chang HS, Yamato O, Yamasaki M, Maede Y (2005) Modulatory influence of sodium 2-propenyl thiosulfate Irom garlic on cyclooxygenase activity in canine platelets possible mechanism for the anti-aggregatray effect. Prostaglandins Leukot Essent Fatty Acids 72(5) 351-355.doi 10.1016/j.plefa.2005.01.003... 

Aqueous extracts of raw garlic also inhibited cyclooxygenase activity in rabbit platelets, again contributing to an antithrombotic effect. In addition, AGE and S-allyl cysteine and S-allyl mercapto-cysteine have antiplatelet adhesion effects. Platelet adhesion to the endothelial surface is involved in atherosclerosis initiation. Furthermore, S-allyl mercaptocysteine inhibits the proliferation of rat aortal smooth muscle cells, another important... 

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