Thromboxane effects

Leger, C.L. et al., A thromboxane effect of a hydroxytyrosol-rich olive oil waste-water extracts in patients with uncomphcated tjfpe 1 diabetes, Eur. J. Clin. Nutr., 59, 727, 2005. 

In healthy blood vessels, prostacyclin is produced which counteracts the thromboxane effect on cAMP levels and, therefore, reduces platelet adhesion. In artifical or damaged vessels the thromboxane effect is unopposed and adhesion takes place. 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

Few areas of organic medicinal chemistry in recent memory have had so many closely spaced pulses of intense research activity as the prostaglandins. Following closely on the heels of the discovery of the classical monocyclic prostaglandins (prostaglandin El, F2, A2, etc.), with their powerful associated activities, for example, oxytocic, blood pressure regulating, and inflammatory, was the discovery of the bicyclic analogues (the thromboxanes, prostacyclin) with their profound effects on hemodynamics and platelet function. More recently, the non-... 

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). 

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 ... 

Banerjee AK, Peters TJ Experimental nonsteroidal anti-inflammatory drug-induced enteropathy in the rat Similarities to inflammatory bowel disease and effect of thromboxane synthetase inhibitors. Gut 1990 3 i 1358— 1364. 

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

Poland, platelet-inhibiting effects have been observed with bisarylpyridazines of type (70, R = H, Me, Br, Cl R2 = H, Me) [270]. In France, the arylidenedi-hydropyridazines (71) and (72) have been investigated [271, 272]. They have been found to inhibit thromboxane biosynthesis. 

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