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Polyphenols and oxidative stress. The risk of cardiovascular disease.
Oxidative stress in the vasculature is a potential target for pharmacologic therapy to prevent atherosclerosis and its complications. Epidemiologic evidence from prospective cohort studies indicate that consumption of fruits and vegetables is associated with a reduced risk of cardiovascular disease. Flavonoids, polyphenols present in fruits and vegetables, are potent antioxidants, and among them quercetin and its derivatives are known to have the highest bioavailability. Antioxidants are designed to neutralize the effects of reactive oxygen species generated in vivo by the normal metabolism of oxygen and other free radicals, and quercetin has been shown to be as efficient as vitamin C in scavenging superoxide and hydroperoxide free radicals. Antioxidant properties of quercetin are also reflected by its ability to enhance the activity of enzymes that scavenge reactive oxygen species, such as superoxide dismutase and catalase. Although epidemiologic studies show a significant protective effect of antioxidant consumption on cardiovascular disease, the experimental evidence is equivocal. We have shown that quercetin (1 mM) scavenges peroxynitrite free radicals, and in vivo pretreatment with quercetin inhibits high-glucose-induced activation of Akt/protein kinase B and endothelial nitric oxide synthase phosphorylation in rat aortic endothelial cells. On the other hand, in vitro study with human umbilical vein endothelial cells indicates that quercetin significantly inhibits oxidative stress induced by H2O2 but not by peroxynitrite, pointing to a minor role of peroxynitrite in endothelial cell oxidative stress in vivo. Thus, at the doses studied, quercetin has no effect on the initial endothelial dysfunction in high-glucose conditions. In addition, quercetin is very efficient in quenching peroxynitrite free radicals produced by endothelial cells but is less active in quenching superoxide and hydroperoxide free radicals. These results indicate that quercetin can effectively scavenge reactive oxygen species produced by the endothelium but at relatively high concentrations in the circulation. Therefore, quercetin is unlikely to exert a direct protective effect on the endothelium.Anne-Marie Walters, who starred as Anna Maxwell-Scott’s vengeful lesbian stepmother Esme Butter in be359ba680
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