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Objective: To determine the potential antioxidant effect of rutin (quercetin-3-O-beta-rutinoside) supplementation., Design: A 6-week randomized single-blind placebo controlled trial was conducted; 500 mg rutin supplement was compared to an equivalent amount of glucose placebo. In addition, a pharmacokinetic study was carried out., Setting: The Rowett Research Institute, Aberdeen, UK., Subjects: Eighteen healthy non-obese normocholesterolaemic female volunteers in the age range 18-48 y., Main Outcome Measures: Plasma flavonoids, ascorbic acid, tocopherols and carotenoids, plasma antioxidant capacity, lymphocyte DNA damage, blood chemistry and haematology, liver function tests, urinary malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-iso-prostaglandin F2alpha., Results: Eighteen volunteers completed the trial. Rutin supplementation did not induce any adverse changes in blood chemistry or indices of liver function. Plasma flavonoids were significantly elevated in the rutin-supplemented group. Endogenous oxidation of pyrimidines was significantly decreased in both rutin- and placebo-treated volunteers. There was no significant change in the level of urinary 8-hydroxy-2'-deoxyguanosine or urinary malondialdehyde in either group. A linear correlation was observed between urinary malondialdehyde and urinary 8-iso-prostaglandin F2alpha (R = 0.54, P<0.01)., Conclusion: Six weeks' rutin supplementation significantly elevated the levels of three plasma flavonoids (quercetin. kaempferol and isorhamnetin) but there was no significant change in plasma antioxidant status. The decrease in the level of endogenous base oxidation in lymphocyte DNA seen in both the placebo- and rutin-supplemented subjects may reflect seasonal changes in other dietary antioxidants.

Background: It is widely believed that antioxidant micronutrients obtained from fruit and vegetables afford significant protection against cancer and heart disease, as well as ageing. Flavonoids are potential antioxidants found in foods such as onions; information on their effectiveness in vivo is so far lacking., Aims: To determine uptake as well as in vivo antioxidant effects of flavonoids from foods., Methods: Six healthy non-obese normocholesterolaemic female volunteers in the age range 20-44 years participated in a randomised two-phase crossover supplementation trial to compare the antioxidant effects associated with (a) a meal of fried onions and (b) a meal of fried onions and fresh cherry tomatoes. Plasma flavonoids, lymphocyte DNA damage, plasma ascorbic acid, tocopherols and carotenoids, urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine were determined to assess flavonoid absorption and antioxidant efficacy., Results: Flavonoid glucosides (quercetin-3-glucoside and isorhamnetin-4-glucoside) were significantly elevated in plasma following ingestion of the onion meal and the increases were associated with an increased resistance of lymphocyte DNA to DNA strand breakage. A significant decrease in the level of urinary 8-hydroxy-2'-deoxyguanosine was evident at 4 h following ingestion of the onion meal. After the combined tomato and onion meal, only quercetin was detected in plasma. Endogenous base oxidation was decreased but resistance to strand breakage was unchanged. There was no significant change in the excretion of urinary malondialdehyde following either meal., Conclusion: Both meals--onions, and onions together with tomatoes--led to transient decreases in biomarkers of oxidative stress, although the particular biomarkers affected differ. It is possible that the differences in patterns of response reflect the different uptakes of flavonoids but the underlying mechanism is not understood.

Background & Aims: Epidemiological studies suggest that antioxidant polyphenols in the human diet may protect against diseases such as cancer. In this study we investigated the cytoprotective potential of the flavonoids, quercetin, myricetin, kaempferol and rutin against oxidative DNA damage in human colonocytes in vitro., Methods: Caco-2 cells, which display specialised enterocyte/colonocyte cell functions, were used as an in vitro model for human colonocytes. Hydrogen peroxide was employed as the oxidant. DNA damage (strand breakage, oxidised purines and oxidised pyrimidines) was determined using the alkaline single cell gel electrophoresis or comet assay. Cell growth and viability were measured., Results: Hydrogen peroxide caused a dose-dependent increase in DNA strand breakage in human colonocytes, presumably via oxygen free radical generation. Quercetin and myricetin protected Caco-2 cells against oxidative attack. In addition, quercetin decreased hydrogen peroxide-mediated inhibition of growth. Neither rutin nor kaempferol was effective. However, quercetin, while inhibiting DNA strand breakage, did not alter the levels of oxidised bases following peroxide treatment. The antifungal agent ketoconazole, prevented quercetin cytoprotection in Caco-2 cells, indicating that P450-mediated metabolism may alter the efficacy of the flavonoids against oxidative DNA damage., Conclusion: Flavonoids, particularly quercetin, the most abundant flavonoid in the human diet, are likely to be important in defending human colonocytes from oxidative attack.

The effects of the flavonoids quercetin and myricetin, and the antihepatotoxic agent silymarin, on hydrogen peroxide-mediated DNA damage in human lymphocytes were determined using alkaline single-cell gel electrophoresis (the comet assay). Treatment with hydrogen peroxide increased the levels of DNA strand breaks and oxidised pyrimidine bases in these cells. Quercetin was protective at concentrations above 10 microM and myricetin decreased oxidant-induced DNA strand breakage at concentrations of 100 microM. Cellular metabolism may alter the antioxidant efficacy of the flavonoids. Silymarin had no protective effect at any of the concentrations tested. None of these flavonoids was itself genotoxic. Neither alpha-tocopherol nor beta-carotene decreased hydrogen peroxide-induced DNA breakage. The differences in effectiveness of these dietary compounds against oxidative DNA damage may be explained by differences in their chemical structure or location within the cell.

The effects of the flavonoids quercetin, myricetin and silymarin on DNA damage and cytotoxicity in human cells were investigated. DNA strand breaks and oxidised pyrimidines were determined using alkaline single cell gel electrophoresis (the comet assay). Inhibition of cell growth was also measured. Caco-2 (colon), HepG2 (liver), HeLa (epithelial) cells and normal human lymphocytes showed different, dose-dependent susceptibilities (in terms of strand breakage) to the various flavonoids, quercetin being the most damaging. This agreed well with the ability of the flavonoids to inhibit cell growth. None of the flavonoids induced DNA base oxidation above background levels. All of the flavonoids under investigation caused depletion of reduced glutathione, which, in the case of quercetin, occurred prior to cell death. Neither cytotoxicity nor genotoxicity was associated with the antioxidant enzyme capacity (glutathione, glutathione reductase, glutathione peroxidase and catalase) of the cells.