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Dietary Polyphenols and the Prevention of Diseases

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Dietary Polyphenols and the Prevention of Diseases ( dietary-polyphenols-and-prevention-diseases )

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290 A. SCALBERT ET AL. concentrations of oxidised lipids, as measured by reaction with thiobarbituric acid.35 In contrast, the consumption of red wine (200 mL per d for 10 d) had no significant effect on plasma MDA levels.36 The consumption of 55 mg of isoflavones for 8 wk had no effect upon concentrations of F2-isoprostane, a marker of lipid peroxidation.37 The effects of polyphenols on the stability of deoxyribonu- cleic acids (DNA) have also been examined. In vitro, polyphe- nols can have either harmful or protective effects. In the presence of transition metals, such as Cu(II) and Fe(III), phenolic com- pounds induce the breakage of DNA.38,39 Such effects are caused by a reduction of these transition metals that, once reduced, cat- ◦ alyze the formation of hydroxyl radical (OH ) (Fenton reaction). These reactions have also been noted in cultured cells.40 Such breakage of DNA has been considered both beneficial (cyto- toxic and apoptotic effects on tumor cells) and toxic (mutagenic effects on normal cells). Conversely, polyphenols may also protect DNA against degr- adation induced by cytotoxic agents. In vitro, they can inhibit the formation of adducts between activated polycyclic hydrocar- bons and DNA.41 In particular, the antimutagenic properties of ellagic acid have been clearly established, at least in Salmonella typhimurium,42 and have been explained by the formation of in- active adducts between activated carcinogens and ellagic acid,43 or by inhibition of aryl hydrocarbon hydroxylase responsible for the activation of polycyclic hydrocarbons.44 A number of in vivo studies have demonstrated the protective effect of polyphenol consumption against DNA damage. In the rat, wine polyphenols added to the diet protected hepatic DNA against oxidative damage induced by 2-nitropropane.45 Similar effects were observed with ellagic acid, but not epigallocate- chin gallate (EGCG).46 Wine polyphenols added to the diet of rats also reduced basal DNA oxidative damage (without induc- tion) to colonic mucosa.47 Supplementation of rat diet with tea theaflavins and thearubigins protected DNA in the colonic mu- cosa against oxidative damage induced by 1,2-dimethylhydrazi- ne48 and oral administration of black tea to rats inhibited the formation of PhIP-DNA adducts in the colon.49 In humans, the consumption of antioxidants or of fruit and vegetables has been associated with reduced levels of oxidative damage to lymphocytic DNA.50 Similar observations have been made with polyphenol-rich foods or beverages. The consump- tion of 240 mL wine per d for one mo resulted in pronounced reduction in levels of oxidized DNA bases (8-OHdG) in blood leukocytes, in particular, when the volunteers were fed a high- fat diet.51 The consumption of onions (rich in quercetin) with meals helped increase resistance of lymphocytic DNA to ex-vivo induced oxidation and reduced urinary excretion of 8-OHdG.52 The consumption of 400 g of onions and 6 cups of tea per d for 2 wk by diabetic patients also reduced the oxydizability of lymphocytic DNA, as assessed by the Comet assay.53 However, other authors have observed no effects on lymphocytic DNA of a similar diet in healthy volunteers,54 and no effects on urinary excretion of 8-OHdG following consumption of an extract of green tea for 3 wk.55 These contradictory data make difficult the evaluation of the importance of DNA protection by polyphenols for disease prevention, particularly since the relationship be- tween oxidative damage to DNA and disease risk (in particular, risk of cancer) has not been established.56 These difficulties in unravelling antioxidant effects of polyph- enols in vivo may be due to some variations in the status of other antioxidants. It is likely that polyphenols act in synergy with other antioxidants.57 It has been shown in several in vitro studies that the relatively polar polyphenols regenerate or spare lipophilic antioxidants, such as vitamin E.58 Antioxidants effects of polyphenols may be more easily observed when the status in other antioxidants is low. POLYPHENOLS AND CARDIOVASCULAR DISEASE A number of animal studies have demonstrated that the consumption of polyphenols limits the development of athero- matous lesions. Supplementation of drinking water with deal- coholized wine, pomegranate juice, catechins, or quercetin re- duced the size of these lesions in apoE-deficient mice.59−61 These effects are associated with reduced low density lipopro- tein (LDL) uptake by macrophages, lower oxidation of isolated LDL (TBARS method), and decreased susceptibility of LDL to aggregation. Similar results were obtained through supplemen- tation of a cholesterol-enriched diet with an extract of grape seeds rich in proanthocyanidins and administered to rabbits.62 An abundant literature has shown that polyphenols can in- hibit oxidation of LDL in vitro; this type of oxidation is con- sidered to be a key mechanism in atherosclerosis. These an- tioxidant effects result in the decreased oxidation of LDL lipids and of α-tocopherol.63 However, evidence in humans is con- tradictory. Certain studies have shown that the consumption of beverages and foods rich in polyphenols (red wine, cocoa, tea, or pomegranate juice) resulted in reduced susceptibility of LDL to oxidation induced ex vivo by Cu(II).29,64−68 The lower lev- els of oxidation products of phosphatidylcholine (the main lipid found in LDL) observed after consumption of green tea cate- chins in man suggest that polyphenols effectively protect LDL against oxidation.33 However, several other studies have shown no effects of polyphenol consumption on the ex vivo oxidation of LDL.31,36,69−73 In the plasma, polyphenols are largely conju- gated with glucuronide and sulfate groups.3 They are, therefore, polar and, most probably, largely eliminated during the isolation of LDL preceding the ex-vivo oxidation test. This could explain the lack of protection observed in these last studies. This does not exclude the association of some polyphenol aglycones or of some esters with fatty acids to LDL, as has been suggested in an experiment where [3H]-genistein was added to human plasma.74 These antioxidant effects are doubtlessly insufficient in them- selves to account for the suggested protective effects of polyphe- nols against cardiovascular diseases. Tea catechins were shown to inhibit the invasion and proliferation of the smooth muscle cells in the arterial wall, a mechanism that may contribute to slow down the formation of the atheromatous lesion.75,76 Polyphenols

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