Thromboxane formation

The plant is known to contain chelerythrine chloride, which inhibits the aggregation of rabbit platelet in vitro via inhibition on thromboxane formation and phosphoinosi-tides breakdown (30). Chelerythrine, which occurs in members of the family Papaver-aceae, has been reported to inhibit the enzymatic activity of protein kinase C and to exert cell-growth inhibitory effect via the induction of apoptosis in numerous cancer cell lines (31,32). What is the topoisomerase activity of chelerythrine ... 

Ko FN, Wu TS, Lious MJ, Huang TF, Teng CM. Inhibition of platelet thromboxane formation and phosphoinositides breakdown by osthole from Angelica pubescens. Thromb Haemost 1989 62 996-999. 

Ritanserin, another 5-HT2 antagonist, has little or no a-blocking action. It has been reported to alter bleeding time and to reduce thromboxane formation, presumably by altering platelet function. 

The NSAIDs (eg, indomethacin, ibuprofen see Chapter 36) block both prostaglandin and thromboxane formation by reversibly inhibiting COX activity. The traditional NSAIDs are not selective for COX-1 or COX-2. Selective COX-2 inhibitors, which were developed more recently, vary—as do the older drugs—in their degree of selectivity. Indeed, there is considerable variability between (and within) individuals in the selectivity attained by the same dose of the same NSAID. Aspirin is an irreversible COX inhibitor. In platelets, which are anuclear, COX-1 (the only isoform expressed in mature platelets) cannot be restored via protein biosynthesis, resulting in extended inhibition ofTXA2 biosynthesis. 

The NSAIDs (eg, aspirin, indomethacin, ibuprofen) block both prostaglandin and thromboxane formation by inhibiting COX activity. For example, aspirin is a long-lasting inhibitor of platelet COX and of TXA2 biosynthesis because it irreversibly acetylates the enzyme. Once acetylated, platelet COX cannot be restored via protein biosynthesis because platelets lack a nucleus. 

PUFA in liver lipids, thromboxane formation and blood pressure... 

Guivemau M, Meza N, Baija P, and Roman O. (1994). Clinical and experimental study on the long-tem effect of dietary gamma-tinolcnic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. ProsL Leukotrienes Essential Fatty Acids. 51,311-316. 

Seiss W, Scherer B, Bohlig B, Roth P, Kurzman L and Weber PC. (1980). Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during Mackrel diet Lancet 1,441-444. 

Difference between aspirin and other NSAIDs Aspirin covalently modifies platelet COX-1, thus irreversibly blocking thromboxane formation and reducing platelet function for the lifespan of the affected platelet (platelets cannot synthesize new proteins). The inhibitory action of other NSAIDs on platelet COX-1 is not covalent and is eventually reversed when the agents blood levels decline. 

Nicolaou, K.C., Magolda, R.L., Smith, J.B., Aharony, D., Smith, E.F. and Lefer, A.M. (1979). Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation. Proc. Natl Acad. Sci USA, 76, 2566-2570... 

Westwick, J., Fletcher, M.S. and Kakkar, V.V. (1983). Inhibition of thromboxane formation prevents endotoxin-induced renal fibrin deposition in jaundiced rats. In Samuelsson, B., Paoletti, R. and Ramwell, P. (eds.) Advances in Prostaglandin, Thromboxane and Leukotrienne Research, Vol. 12, p. 83-91. (New York Raven Press)... 

Reilly, I.A.G. and FitzGerald, G.A. (1987). Inhibition of thromboxane formation in vivo and ex vivo implications for therapy with platelet inhibitor drugs. Blood, 69, 180-187... 

The compounds helenalin and lla,13-dihydrohelenalin have been shown to inhibit collagen-induced platelet aggregation, thromboxane formation, and 5-hydroxytryptamine secretion in a concentration-dependent manner in human platelets (Schrdder et al. 1990). 

The compound saikosaponin inhibited human platelet aggregation induced by ADP, with a potency of inhibition comparable to that of aspirin, and dose-dependently inhibited platelet thromboxane formation from exogenous and endogenous arachidonic acid. Effects were similar to that of epigallocatechin isolated from green tea (Chang and Hsu 1991). 

Shah, B.H., Z. Nawaz, S.A. Pertani, et al. 1999. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca + signaling. Biochem. Pharmacol. 58(7) 1167-1172. 

Lorenz, R., Spongier, U., Eischer, S., Duhm, J., and Weba , P.C. (1983) Platelet Function, Thromboxane Formation and Blood Pressure Control During Supplementation of the Western Diet with Cod Liver Oil, Circulation 67,504—511. 

Singer, P., Berger, L, Moritz, V., and Taube, C. (1990) N-6 and n-3 PUFA in Liver Lipids, Thromboxane Formation and Blood Pressure from SHR During Diets Supplemented with Evening Primrose, Sunflower Seed or Fish Oil, Prostag. Leukote. Ess. 39,207-211. 

The non-acidic anti-inflammatory compound 2-isopropyl-3-nicotinylindole (L-8027) inhibits thromboxane biosynthesis [114-116] with simultaneous inhibition of PGE formation, indicating that the compound is not a specific inhibitor of thromboxane synthetase [117]. Metopyrone (2-methyl-l,2-di-3-pyridyl-l-propanone), which shares some structural features with L-8027, was reported to inhibit thromboxane formation in microsomes from human platelets and bovine lung [118]. 

The synthetic pyridine derivative, -(4-(2-carboxy-l-propenyl)benzyl) pyridine hydrochloride (OKY-1555) inhibited thromboxane formation selectively and had an IC50 of 3 nM [135]. Also the corresponding sodium salt (OKY-1581) was a potent and selective inhibitor of thromboxane synthetase [137,138]. 

Other factors known to stimulate thromboxane formation by various cell types... 

Among common foodstuffs, onion and garlic have been reported to contain a heat-stable, lipid soluble factor that inhibits platelet aggregation [183-186], This factor inhibits thromboxane synthesis in platelets from exogenous [ C]arachidonic acid. Along with the decreased thromboxane formation, a new metabolite of arachidonic acid appeared, 10-hydroxy-11,12-epoxy-5,8,14-eicosatrienoic acid, probably via the platelet lipoxygenase pathway [185],... 

The generation of thromboxanes caused by histamine or SRS-A can be inhibited in the guinea pig by non-steroidal anti-inflammatory drugs [285], however without significantly reducing the bronchoconstriction [286]. On the other hand, these drugs prevented both the increased airway resistance and the thromboxane formation induced by bradykinin [286]. 

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