The production of reactive oxygen species by dietary flavonols (original) (raw)
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Toxicology, 2002
Dietary polyphenolics in fruits, vegetables, wines, spices and herbal medicines have beneficial antioxidant, anti-inflammatory and anticancer effects. However, we have observed that dietary polyphenolics with phenol rings were metabolized by peroxidase to form prooxidant phenoxyl radicals which, in some cases were sufficiently reactive to cooxidize GSH or NADH accompanied by extensive oxygen uptake and reactive oxygen species formation. The order of catalytic effectiveness found for oxygen activation when polyphenolics were metabolized by peroxidase in the presence of GSH was phloretin \phloridzin\ 4,2%-dihydroxy chalcone \ p-coumaric acid \ naringenin\ apigenin\ curcumin \resveratrol\ isoliquiritigenin\ capsaicin\ kaempferol. Ascorbate was also cooxidized by the phenoxyl radicals but without oxygen activation. Polyphenolics with catechol rings also cooxidized ascorbate, likely mediated by semiquinone radicals. The order of catalytic effectiveness found for ascorbate cooxidation was fisetin, luteolin, quercetin, \eriodictyol, caffeic acid, nordihydroguaiaretic acid \ catechin\taxifolin, catechol. NADH was stoichiometrically oxidized without oxygen uptake which, suggests that o-quinone metabolites were responsible. GSH was not cooxidized and GSH conjugates were formed, likely mediated by the o-quinone metabolites. Incubation of hepatocytes with dietary polyphenolics containing phenol rings was found to partially oxidize hepatocyte GSH to GSSG while polyphenolics with a catechol ring were found to deplete GSH through formation of GSH conjugates. Dietary polyphenolics with phenol rings also oxidized human erythrocyte oxyhemoglobin and caused erythrocyte hemolysis more readily than polyphenolics with catechol rings. It is concluded that polyphenolics containing a phenol ring are generally more prooxidant than polyphenolics containing a catechol ring.
Free Radical Research, 2005
We have analyzed the anti-or pro-oxidant effects of the flavonoid quercetin (QU) by evaluating, in U937 cell line, hydrogen peroxide (H 2 O 2 ), superoxide anion ðO 2 2 Þ; reduced glutathione (GSH) content, mitochondrial membrane potential, DNA content, phosphatidylserine exposure on the outer face of the plasma membrane and cell viability. Polychromatic flow cytometry was used to evaluate in the same cells several functional parameters. For short periods of treatment QU exerted an anti-oxidant effect (decrease in H 2 O 2 levels), whereas for long periods it showed a pro-oxidant activity (increase in O 2 2 ). In these conditions, GSH content was reduced, and this correlated with a lack of anti-oxidant activity of QU, which in turn could be correlated with proapoptotic activity of this molecule. Thus, QU can exert different effects (anti-/prooxidant) depending on exposure times and oxidative balance, and in particular on stores of GSH.
Biochemical …, 1989
The plant-derived phenolic compounds gossypol, quercetin and myricetin are powerful inhibitors of iron-induced lipid peroxidation in rat liver microsomes, under all five experimental conditions tested and at low micromolar concentrations (ICjo < 1.5 yM). However, they greatly accelerate the generation of hydroxyl radicals (*OH) from H,O, in the presence of Fe'+-EDTA at pH7.4, as measured by the deoxyribose assay. At 100 PM, the three phenolic compounds enhanced *OH formation up to eight-fold. The hydroxyi radical generation was inhibited by catalase and superoxide dismutase, suggesting a mechanism in which the phenols oxidize to produce superoxide radical, which then assists *OH generation from HzO, in the presence of Fe '+-EDTA. At concentrations up to 75 PM, quercetin and myricetin also accelerate bleomycin-dependent DNA damage in the presence of Fe3+, possibly by reducing the Fe 3+-bleomycin-DNA complex to the Fe 2t form. Hence these naturally-occurring substances can have nro-oxidant effects under some reaction conditions and cannot be classified simplistically as "antioxidants".
Quercetin as an effective antioxidant against superoxide radical
Functional Food Science, 2023
Background: Quercetin is considered one of the most studied flavonols widely found in fruits and vegetables. Food preparation and storage affect the level of quercetin in food, as these processes can cause a partial or complete reduction in flavonol levels. Quercetin, as a bioactive compound, has beneficial effects on the human body and with various diseases due to its potent antioxidant properties. Quercetin is a scavenger of free radicals and exerts its effects in various body fluids (e.g., saliva, synovial fluid, blood). Because of this, it is essential to know the effect of pH on its antioxidant properties. Objective: This study aims to determine the antioxidant capacity of quercetin against superoxide radicals depending on pH using a spectroscopic method. Methods: The antioxidant properties of quercetin in the concentration range from 5 to 50 μg/ml against superoxide radicals were measured at pH values of 6.5 to 8. Superoxide radicals were generated in the photooxidation reaction of methionine with riboflavin. Inhibition of superoxide radicals by quercetin was detected spectrophotometrically in reaction with NTB. Results: Quercetin is an effective superoxide radical scavenger with the highest antioxidant capacity observed at a slightly acidic pH of 6.5. The antioxidant activity of quercetin increased with increasing concentration; effective antioxidant capacity of quercetin was in the experiment at a concentration above 30 µg/ml. Conclusion: Quercetin is a widely occurring flavonoid with many beneficial effects on the human body related to its antioxidant properties. Quercetin is an effective scavenger of superoxide radicals. Its correct dosage, processing, and storage, which significantly affect the antioxidant properties of quercetin, have a considerable impact on the effects of quercetin in the prevention and treatment of diseases. Since pH significantly affects biochemical processes in living organisms, our results could contribute to expanding information on the antioxidant properties of quercetin as a rich natural source of medicinal substances, depending on pH. Keywords:quercetin, antioxidant, superoxide radical, spectrophotometry
On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions
Analytical and Bioanalytical Chemistry, 2012
The natural flavonoid compounds quercetin (3,3′,4′,5,7-pentahydroxyflavone) and luteolin (3′,4′,5,7tetrahydroxyflavone) are important bioactive compounds with antioxidative, anti-allergic, and anti-inflammatory properties. However, both are unstable when exposed to atmospheric oxygen, which causes degradation and complicates their analytical determinations. The oxidative change of these flavonoids was observed and followed by UV-visible spectrophotometry, both in aqueous and ethanolic solutions. The distribution of the degradation products in aqueous media was monitored by LC-MS and LC-DAD analysis. The amounts of oxidative reaction products increase with the exposure time. The oxidative degradation reduces the pharmacological efficiency of these antioxidants and renders analytical determination inaccurate. The oxidative changes in flavonoid test solutions can explain the inconsistent dissociation constants reported in the literature. Dissociation constants of quercetin and luteolin were determined both by alkalimetric titration and by UV-visible spectrophotometry under deaerated conditions. The values pK 1 =5.87±0.14 and pK 2 =8.48±0.09 for quercetin, and pK 1 =5.99±0.32 and pK 2 = 8.40±0.42 for luteolin were found.
Antioxidant properties of major metabolites of quercetin
European Food Research and Technology, 2011
Dietary flavonoids have been related to health promotion, which has been attributed in part to their antioxidant properties as demonstrated in many in vitro studies. However, in the human organism most flavonoids are little bioavailable and largely transformed to different metabolites that are crucial to explain the health effects associated with their dietary intake, although little is known about their biological activities. Quercetin is a majority flavonoid in the human diet that has been commonly used in studies on the flavonoid and health relationships. In this study, the antioxidant activity of different conjugated metabolites of quercetin (quercetin 3 0 -O-sulphate, quercetin 4 0 -O-sulphate, quercetin 3-O-glucuronide and isorhamnetin 3-O-sulphate) prepared in the laboratory, and of some phenolic acids that may result from its colonic degradation, was investigated by two in vitro assays (ABTS and FRAP assays). As expected, substitution of the hydroxyl groups of quercetin by the conjugating substituents resulted in a decrease in the antioxidant activity with regard to the parent compound. Despite this, the conjugated metabolites still retained significant antioxidant activity and behave as significantly better radical scavengers and reducing compounds than usually recognized antioxidants like a-tocopherol. Greater antioxidant activity of the metabolites was found in the ABTS assay, conducted at pH 7.4, suggesting that quercetin derivatives could act as potential radical scavengers in physiological conditions. Similarly, antioxidant activity significantly higher than a-tocopherol was also found in the ABTS assay for 3,4-dihydroxyphenylacetic, 3-methoxy-4hydroxyphenylacetic and 3-(3,4-dihydroxyphenyl)propionic acids, described as products of the colonic degradation of quercetin. Phenylacetic acids were more active than benzoic and phenylpropionic acids, and the activity increased with the number of phenolic hydroxyls in the molecule; methoxylated derivatives showed, in general, lower activity than the equivalent O-dihydroxylated forms but greater than that of the monohydroxylated precursor. The results obtained are expected to contribute to the understanding of the mechanisms involved in the biological effects associated with the intake of flavonoid-rich diets.
The oxidation of natural flavonoid quercetin
Chemical Communications, 2012
This study explains the controversies in the literature concerning the number of electrons involved in the oxidation of quercetin. This stems from inappropriate handling samples, which require strict anaerobic conditions. The redox potential of quercetin strongly depends on the pH and on the presence of dissociation forms in solution.
Inhibition of oxidative hemolysis by quercetin, but not other antioxidants
Chemico-Biological Interactions, 2010
We previously reported that lipid-soluble quercetin, not water-soluble dihydroquercetin, protects human red blood cells against oxidative damage. The objectives of this study were to determine if an antihemolytic effect could be produced by other lipid-soluble antioxidants and if anti-inflammatory activity played a role in antihemolysis by quercetin. This study compared three lipid-soluble polyphenols, muscadine, curcumin and quercetin, and three lipid-(␣-tocopherol and ␣-tocotrienol) or watersoluble (ascorbic acid) vitamins. Among the tested polyphenols, muscadine was the most potent in inhibiting superoxide and 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH)-generated peroxyl radicals, whereas ascorbic acid was the most potent inhibitor of hydrogen peroxide. Activities of the polyphenols after lipid extractions showed that curcumin inhibited superoxide production to a greater extent than quercetin and muscadine. All blood cells were tested 20 min after incubation with the selected compounds. All the polyphenols caused inhibition of N-formyl-l-methionyl-l-leucyl-lphenylalanine-induced neutrophil oxidative bursts. Quercetin, but not other polyphenols, significantly reduced AAPH-induced oxidative hemolysis. No significant effect on neutrophil oxidative burst or oxidative hemolysis was found with any of the tested vitamins. These results suggest that quercetin enhances the resistance of membrane to destruction by free radicals. This effect of quercetin is not directly mediated through antioxidative or anti-inflammatory actions. Antioxidant or anti-inflammatory potency may not be used as a simple criterion to select polyphenols for cell protection benefits.
Iron reduction potentiates hydroxyl radical formation only in flavonols
Food chemistry, 2012
Flavonoids, substantial components of the human diet, are generally considered to be beneficial. However, they may possess possible pro-oxidative effects, which could be based on their reducing potential. The aims of this study were to evaluate the ability of 26 flavonoids to reduce ferric ions at relevant pH conditions and to find a possible relationship with potentiation of hydroxyl radical production. A substantial ferric ions reduction was achieved under acidic conditions, particularly by flavonols and flavanols with the catecholic ring B. Apparently corresponding bell-shaped curves displaying the pro-oxidant effect of flavonols quercetin and kaempferol on iron-based Fenton reaction were documented. Several flavonoids were efficient antioxidants at very low concentrations but rather inefficient or pro-oxidative at higher concentrations. Flavonols, morin and rutin were progressively pro-oxidant, while 7-hydroxyflavone and hesperetin were the only flavonoids with dose-dependent inhibition of hydroxyl radical production. Conclusively, administration of flavonoids may lead to unpredictable consequences with few exceptions.