where:
R is an organic molecule
ROOH is an organic peroxide
R:R are two organic molecules which have been cross-linked to-
gether
Oz is oxygen
Cu is copper, Fe is iron
*is the unpaired electron
H is a hydrogen atom
HO* is a superoxide free radical
RO,* and R* are organic free radicals
Note that two free radicals can terminate their own chain reaction by combining. The resulting combination is stable, not a free radical, because the two electrons are paired.
Compounds that can help terminate the chain of free radical reactions are called free radical quenchers or scavengers. Antioxidants such as vitamins A, E, and C, the sulfur containing amino acid cysteine, the cysteine-containing triamino acid glutathione, the phenolic and catecholic amino
acids such as tyrosine and L-Dopa, the mineral selenium, and synthetic antioxidants such as BHT, BHA, and ethoxyquin are effective free radical quenchers. Aging is due, in part, to the decrease in blood and tissue levels of antioxidants that occurs in aging.
Since free radicals are able to cause genetic mutations, they have been implicated in the genesis of atherosclerotic plaques (a type of tumor) and cancer. Free radical quenchers such as C, E, BHA, BHT, selenium, and cysteine have been shown in experimental animals to prevent the development of some types of cancer. Peroxidized fats, the most common type of organic peroxide, are a source of free radicals (they also inhibit macrophages, white cells of the immune system, so that they do not attack and eat foreign invaders such as bacteria and cancer cells). Overweight individuals, who contain a larger amount of peroxidized fats in their body, are more likely to develop cancer and atherosclerosis than people
of normal weight.
Peroxidized fats—found plentifully in atherosclerotic plaques—inhibit the production of PGI, PGI, was discovered by Vane and Moncada, for which they received the prestigious Lasker research award. PGI. (also called prostacyclin) is the natural hormone which prevents abnormal blood clots. If there is not enough PGl, a clot forms on the artery wall. Iron and copper leak from the hemolyzing red blood cells in the clot and promote the free radical peroxidation of still more fats, further decreasing PGIs, and so the clot grows. After a while, part of the clot may break off. If it lodges in your coronary artery, you have a heart attack—coronary thrombosis. If
it lodges in your brain, you have a stroke and suffer brain damage. In his clinical practice, Dr. Wilfred E. Shute has been using megadoses of vitamin E in humans for forty years to prevent abnormal clots, heart attacks, and strokes. Now that it is understood how the E works (it helps prevent the forma- tion of the peroxidized fats), it will probably become used
much more widely for these purposes.
Figures 1a and 1b illustrate the delicate balance between the formation of blood clots and their prevention. In Figure 1a we see an endothelial cell (lining an artery), with the enzyme prostacyclin synthetase manufacturing prostacyclin (PGI,) to prevent blood from clotting inside the artery. A
platelet in the bloodstream is shown making thromboxane, which causes blood to clot. In Figure 1b we see that a lipid (fat) peroxide has knocked out the prostacyclin synthetase, resulting in a drastic reduction in prostacyclin manufacture. In the meantime, the platelet increases production of thromboxane, resulting in abnormal blood clots which can cause heart
attack or stroke.
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