A Review of the Antioxidant Mechanisms of Polyphenol Compounds Related to Iron Binding

In this review, primary attention is given to the antioxidant (and prooxidant) activity of polyphenols arising from their interactions with iron both in vitro and in vivo. In addition, an overview of oxidative stress and the Fenton reaction is provided, as well as a discussion of the chemistry of iron binding by catecholate, gallate, and semiquinone ligands along with their stability constants, UV–vis spectra, stoichiometries in solution as a function of pH, rates of iron oxidation by O2 upon polyphenol binding, and the published crystal structures for iron–polyphenol complexes. Radical scavenging mechanisms of polyphenols unrelated to iron binding, their interactions with copper, and the prooxidant activity of iron–polyphenol complexes are briefly discussed.

[1]  A. Zehnder,et al.  Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. , 2001, Environmental microbiology.

[2]  C. Ruxton,et al.  Black tea – helpful or harmful? A review of the evidence , 2007, European Journal of Clinical Nutrition.

[3]  N. Seeram,et al.  Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. , 2008, Journal of agricultural and food chemistry.

[4]  K. Murakami,et al.  Interaction of iron with polyphenolic compounds: application to antioxidant characterization. , 1998, Analytical biochemistry.

[5]  M. Hermes-Lima,et al.  The antioxidant effect of tannic acid on the in vitro copper-mediated formation of free radicals. , 2005, Archives of biochemistry and biophysics.

[6]  G. Ackermann,et al.  Über Eisen(III)‐Komplexe mit Phenolen. IV. Säurekonstanten einiger Polyphenole , 1970 .

[7]  P. George The oxidation of ferrous perchlorate by molecular oxygen , 1954 .

[8]  D. Dickinson,et al.  Green Tea Polyphenol Causes Differential Oxidative Environments in Tumor versus Normal Epithelial Cells , 2003, Journal of Pharmacology and Experimental Therapeutics.

[9]  I. Arts,et al.  Catechin contents of foods commonly consumed in The Netherlands. 2. Tea, wine, fruit juices, and chocolate milk. , 2000, Journal of agricultural and food chemistry.

[10]  S. Kawanishi,et al.  Histone peptide AKRHRK enhances H(2)O(2)-induced DNA damage and alters its site specificity. , 2005, Biochemical and biophysical research communications.

[11]  B. Halliwell,et al.  Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. , 1989, Biochemical pharmacology.

[12]  M. C. Taylor,et al.  Interactions of iron(II) and iron(III) with gallic acid and its homologues: a potentiometric and spectrophotometric study , 1982 .

[13]  A. Takashima,et al.  Potent anti‐amyloidogenic and fibril‐destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease , 2003, Journal of neurochemistry.

[14]  S. Kallithraka,et al.  The effect of polyphenolic composition as related to antioxidant capacity in white wines , 2003 .

[15]  K. Riganakos,et al.  Protection against nuclear DNA damage offered by flavonoids in cells exposed to hydrogen peroxide: the role of iron chelation. , 2005, Free radical biology & medicine.

[16]  A. Bast,et al.  A new approach to assess the total antioxidant capacity using the TEAC assay , 2004 .

[17]  Y. Hara,et al.  Iron complexes of gallocatechins. Antioxidant action or iron regulation , 1998 .

[18]  S. Mandel,et al.  Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. , 2006, Molecular nutrition & food research.

[19]  D. Flint,et al.  The inactivation of Fe-S cluster containing hydro-lyases by superoxide. , 1993, The Journal of biological chemistry.

[20]  S. Shohet,et al.  Lipid membrane peroxidation in beta-thalassemia major. , 1976, Blood.

[21]  W. Mcbryde A SPECTROPHOTOMETRIC REEXAMINATION OF THE SPECTRA AND STABILITIES OF THE IRON (III) – TIRON COMPLEXES , 1964 .

[22]  I. Slaninová,et al.  Influence of dietary phenolic acids on redox status of iron: Ferrous iron autoxidation and ferric iron reduction , 2008 .

[23]  I. Fridovich,et al.  An enzyme-based theory of obligate anaerobiosis: the physiological function of superoxide dismutase. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. Leeuwenburgh,et al.  Aging and the Role of Reactive Nitrogen Species , 2002, Annals of the New York Academy of Sciences.

[25]  S. Sasaki,et al.  Selective Fluorescence Detection Of 8-Oxoguanosine With 8-Oxog-Clamp , 2007, Nucleosides, nucleotides & nucleic acids.

[26]  L. Hallberg,et al.  Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron absorption in men. , 1991, The American journal of clinical nutrition.

[27]  W. Kaim,et al.  Enhanced hydroxyl radical production by dihydroxybenzene-driven Fenton reactions: implications for wood biodegradation , 2007, JBIC Journal of Biological Inorganic Chemistry.

[28]  Christopher J. Chang,et al.  Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging , 2008 .

[29]  S. Linn,et al.  Formation, Prevention, and Repair of DNA Damage by Iron/Hydrogen Peroxide* , 1997, The Journal of Biological Chemistry.

[30]  S. Kuo,et al.  Dietary flavonoids interact with trace metals and affect metallothionein level in human intestinal cells , 1998, Biological Trace Element Research.

[31]  J. Rivas-Gonzalo,et al.  Quantitative analysis of flavan-3-ols in Spanish foodstuffs and beverages. , 2000, Journal of agricultural and food chemistry.

[32]  N. Hadjiliadis Cytotoxic, mutagenic, and carcinogenic potential of heavy metals related to human environment , 1997 .

[33]  W R Markesbery,et al.  Oxidative stress hypothesis in Alzheimer's disease. , 1997, Free radical biology & medicine.

[34]  I. Cheng,et al.  On the ability of four flavonoids, baicilein, luteolin, naringenin, and quercetin, to suppress the fenton reaction of the iron-ATP complex , 2000, Biometals.

[35]  Bo Zhou,et al.  Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu(II) ions: mechanism and structure-activity relationship. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[36]  R. Wood The iron–heart disease connection: is it dead or just hiding? , 2004, Ageing Research Reviews.

[37]  S. Mandel,et al.  The Essentiality of Iron Chelation in Neuroprotection: A Potential Role of Green Tea Catechins , 2005 .

[38]  J. García-Mina,et al.  Electrochemical and theoretical complexation studies for Zn and Cu with individual polyphenols , 2005 .

[39]  S. Sang,et al.  Possible controversy over dietary polyphenols: benefits vs risks. , 2007, Chemical research in toxicology.

[40]  R. Meneghini,et al.  Correlation between cytotoxic effect of hydrogen peroxide and the yield of DNA strand breaks in cells of different species. , 1984, Biochimica et biophysica acta.

[41]  P Riederer,et al.  Selective Increase of Iron in Substantia Nigra Zona Compacta of Parkinsonian Brains , 1991, Journal of neurochemistry.

[42]  M. Linares,et al.  Increased susceptibility of microcytic red blood cells to in vitro oxidative stress , 1995, European journal of haematology.

[43]  Erin E. Battin,et al.  The central role of metal coordination in selenium antioxidant activity. , 2006, Inorganic chemistry.

[44]  A. Wang,et al.  Crystallographic studies of metal ion-DNA interactions: different binding modes of cobalt(II), copper(II) and barium(II) to N7 of guanines in Z-DNA and a drug-DNA complex. , 1993, Nucleic acids research.

[45]  O. Dangles,et al.  Interactions of quercetin with iron and copper ions: Complexation and autoxidation , 2006, Free radical research.

[46]  M. Elhabiri,et al.  Complexation of iron(III) by catecholate-type polyphenols , 2007 .

[47]  Lubin,et al.  Lipid Membrane Peroxidation in fl-Thalassemia Major , 2005 .

[48]  Julia L. Brumaghim,et al.  Predicting how polyphenol antioxidants prevent DNA damage by binding to iron. , 2008, Inorganic chemistry.

[49]  Qiang He,et al.  Effects of tea polyphenols on the activities of α-amylase, pepsin, trypsin and lipase , 2007 .

[50]  Patrick M. Wright,et al.  Repair of oxidative DNA damage , 2007, Cell Biochemistry and Biophysics.

[51]  H. Ohshima,et al.  Induction of DNA strand breakage and base oxidation by nitroxyl anion through hydroxyl radical production. , 1999, Free radical biology & medicine.

[52]  R. Hider,et al.  Model compounds for microbial iron-transport compounds. Part 1. Solution chemistry and Mössbauer study of iron(II) and iron(III) complexes from phenolic and catecholic systems , 1981 .

[53]  L. Baum,et al.  Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. , 2004, Journal of Alzheimer's disease : JAD.

[54]  E. Sussuchi,et al.  Synthesis, Electrochemical, Spectral, and Antioxidant Properties of Complexes of Flavonoids with Metal Ions , 2003 .

[55]  J. Imlay,et al.  Superoxide accelerates DNA damage by elevating free-iron levels. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[56]  I. Rietjens,et al.  pH-Dependent radical scavenging capacity of green tea catechins. , 2008, Journal of agricultural and food chemistry.

[57]  R. Ratan,et al.  The role of iron neurotoxicity in ischemic stroke , 2004, Ageing Research Reviews.

[58]  E. Dierenfeld,et al.  Research Article: Tannin/Polyphenol effects on iron solubilization in vitro , 2004 .

[59]  D. Wemmer,et al.  Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences , 2005, Nucleic acids research.

[60]  T. O’Halloran,et al.  Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. , 1999, Science.

[61]  O. Aruoma,et al.  Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide. , 1991, The Biochemical journal.

[62]  A. Deisseroth,et al.  Catalase: Physical and chemical properties, mechanism of catalysis, and physiological role. , 1970, Physiological reviews.

[63]  W. Pryor,et al.  The formation of peroxynitrite in vivo from nitric oxide and superoxide. , 1995, Chemico-biological interactions.

[64]  Thomas M. Garrett,et al.  Ferric ion sequestering agents. 17. Macrobicyclic iron(III) sequestering agents , 1987 .

[65]  M. Velusamy,et al.  Iron(III) complexes of sterically hindered tetradentate monophenolate ligands as functional models for catechol 1,2-dioxygenases: the role of ligand stereoelectronic properties. , 2004, Inorganic chemistry.

[66]  Ashley I. Bush,et al.  The metallobiology of Alzheimer's disease , 2003, Trends in Neurosciences.

[67]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[68]  A. Chatterjee,et al.  Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress , 2006, BMC Cancer.

[69]  K. Raymond,et al.  Solution equilibria of enterobactin and metal-enterobactin complexes , 1991 .

[70]  M. Hynes,et al.  The kinetics and mechanisms of the reaction of iron(III) with gallic acid, gallic acid methyl ester and catechin. , 2001, Journal of inorganic biochemistry.

[71]  Daniel Steinberg,et al.  Low Density Lipoprotein Oxidation and Its Pathobiological Significance* , 1997, The Journal of Biological Chemistry.

[72]  P. George Some experiments on the reactions of potassium superoxide in aqueous solutions , 1947 .

[73]  L. Que,et al.  Models for extradiol cleaving catechol dioxygenases: syntheses, structures, and reactivities of iron(II)-monoanionic catecholate complexes. , 2001, Inorganic chemistry.

[74]  John R. Whitaker,et al.  The biochemistry and control of enzymatic browning , 1995 .

[75]  G. Lescoat,et al.  Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. , 1993, Biochemical pharmacology.

[76]  K. Umegaki,et al.  Physiological Concentrations of ( (cid:1) )-Epigallocatechin-3- O -Gallate (EGCg) Prevent Chromosomal Damage Induced by Reactive Oxygen Species in WIL2-NS Cells , 2002 .

[77]  Henry Jay Forman,et al.  Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. , 2002, American journal of respiratory and critical care medicine.

[78]  Ze'ev Ronai,et al.  Role of redox potential and reactive oxygen species in stress signaling , 1999, Oncogene.

[79]  A. Mayer Polyphenol Oxidases in Plants and Fungi: Going Places? A Review , 2007 .

[80]  F. Gutiérrez,et al.  Contribution of polyphenols to the oxidative stability of virgin olive oil , 2001 .

[81]  R. Huffman,et al.  KINETICS OF THE FERROUS IRON-OXYGEN REACTION IN SULFURIC ACID SOLUTION , 1956 .

[82]  S. Davis,et al.  Metallothionein expression in animals: a physiological perspective on function. , 2000, The Journal of nutrition.

[83]  E. Matuschek,et al.  Oxidation of polyphenols in phytate-reduced high-tannin cereals: effect on different phenolic groups and on in vitro accessible iron. , 2001, Journal of agricultural and food chemistry.

[84]  W. Malaisse,et al.  The stimulus-secretion coupling of glucose-induced insulin release , 1979, Diabetologia.

[85]  E. Rivière,et al.  Spin crossover of ferric complexes with catecholate derivatives. Single-crystal X-ray structure, magnetic and Mössbauer investigations. , 2005, Dalton transactions.

[86]  G. Oboh,et al.  DISTRIBUTION AND ANTIOXIDANT ACTIVITY OF POLYPHENOLS IN RIPE AND UNRIPE TREE PEPPER (CAPSICUM PUBESCENS) , 2007 .

[87]  J. Imlay,et al.  Quantitation of intracellular free iron by electron paramagnetic resonance spectroscopy. , 2002, Methods in enzymology.

[88]  G. Brewer,et al.  Iron and Copper Toxicity in Diseases of Aging, Particularly Atherosclerosis and Alzheimer’s Disease , 2007, Experimental biology and medicine.

[89]  小泉雅彦 A Marked Increase in Free Copper Levels in the Plasma and Liver of LEC Rats: an Animal Model for Wilson Disease and Liver Cancer(LECラット血漿・肝臓中の遊離銅の顕著な増加: ウィルソン病・肝癌の動物モデル) , 1998 .

[90]  May-Chen Kuo,et al.  Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[91]  K. Raymond,et al.  Ferric Ion Sequestering Agents. Part 15. Synthesis, Solution Chemistry, and Electrochemistry of a New Cationic Analogue of Enterobactin. , 1987 .

[92]  D. Touati,et al.  Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase , 1995, Journal of bacteriology.

[93]  S. Linn,et al.  Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions Has Possible Biological Implications* , 1999, The Journal of Biological Chemistry.

[94]  G. Tarzia,et al.  Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism. , 2002, The Biochemical journal.

[95]  C. Winterbourn The ability of scavengers to distinguish OH. production in the iron-catalyzed Haber-Weiss reaction: comparison of four assays for OH. , 1987, Free radical biology & medicine.

[96]  H N Graham,et al.  Green tea composition, consumption, and polyphenol chemistry. , 1992, Preventive medicine.

[97]  H. Poulsen,et al.  Quantification of 8-oxo-guanine and guanine as the nucleobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry. , 2002, Nucleic acids research.

[98]  D. Sreeramulu,et al.  Addition of Milk Does Not Alter the Antioxidant Activity of Black Tea , 2005, Annals of Nutrition and Metabolism.

[99]  E. Mentasti,et al.  Interactions of Fe(III) with adrenaline, l-dopa and other catechol derivatives: Electron-exchange kinetics and mechanism in acidic perchlorate media , 1976 .

[100]  K. Kikugawa,et al.  Effect of plant phenolics on the formation of the spin-adduct of hydroxyl radical and the DNA strand breaking by hydroxyl radical. , 1996, Biological & pharmaceutical bulletin.

[101]  R. Touyz,et al.  Reactive oxygen species, cell growth, cell cycle progression and vascular remodeling in hypertension. , 2007, Future cardiology.

[102]  K. Raymond,et al.  The Self‐Assembly of a Predesigned Tetrahedral M4L6 Supramolecular Cluster , 1998 .

[103]  大川 博,et al.  Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction , 1979 .

[104]  S. Khokhar,et al.  Iron binding characteristics of phenolic compounds: some tentative structure–activity relations , 2003 .

[105]  New Insights on the Anticancer Properties of Dietary Polyphenols , 2007 .

[106]  M. Inoue,et al.  Antioxidant, gallic acid, induces apoptosis in HL-60RG cells. , 1994, Biochemical and biophysical research communications.

[107]  M. Nair,et al.  Structure-activity relationships for antioxidant activities of a series of flavonoids in a liposomal system. , 1998, Free radical biology & medicine.

[108]  K. Jensen,et al.  Biodegradative mechanism of the brown rot basidiomycete Gloeophyllum trabeum: evidence for an extracellular hydroquinone‐driven fenton reaction , 1999, FEBS letters.

[109]  E. Feskens,et al.  Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study , 1993, The Lancet.

[110]  C. Filesi,et al.  Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. , 2005, The Journal of nutritional biochemistry.

[111]  G. Bellomo,et al.  Free radical-scavenging properties of olive oil polyphenols. , 1998, Biochemical and biophysical research communications.

[112]  J. S. Brimacombe,et al.  Structure-activity relationships in the induction of single-strand breakage in plasmid pBR322 DNA by amino sugars and derivatives. , 1994, Carbohydrate research.

[113]  R. Mason,et al.  Hydroxyl radical formation from cuprous ion and hydrogen peroxide: a spin-trapping study. , 1995, Archives of biochemistry and biophysics.

[114]  G. Lee,et al.  Oxygenation of Ferrous Iron , 1961 .

[115]  S. Srichairatanakool,et al.  Iron-Chelating and Free-Radical Scavenging Activities of Microwave-Processed Green Tea in Iron Overload , 2006, Hemoglobin.

[116]  N. Sugihara,et al.  Anti- and pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid. , 1999, Free radical biology & medicine.

[117]  L. Novotný,et al.  Determination of free radical scavenging activity of quercetin, rutin, luteolin and apigenin in H2O2-treated human ML cells K562. , 2004, Neoplasma.

[118]  A. D. de Grey A proposed refinement of the mitochondrial free radical theory of aging. , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[119]  J. Schrezenmeir,et al.  Addition of milk prevents vascular protective effects of tea. , 2007, European heart journal.

[120]  L. Packer,et al.  Iron coordination by catechol derivative antioxidants. , 1996, Biochemical pharmacology.

[121]  K. Raymond,et al.  Ferric ion sequestering agents. 3. The spectrophotometric and potentiometric evaluation of two new enterobactin analogs: 1,5,9-N,N',N''-tris(2,3-dihydroxybenzoyl)cyclotriazatridecane and 1,3,5-N,N',N''-tris(2,3-dihydroxybenzoyl)triaminomethylbenzene , 1979 .

[122]  T. Hambley,et al.  Synthesis, X-ray Structural Determination, and Magnetic Susceptibility, Mössbauer, and EPR Studies of (Ph4P)2[Fe2(Cat)4(H2O)2]·6H2O, a Catecholato-Bridged Dimer of Iron(III) , 1996 .

[123]  Q. Fernaǹdo,et al.  Potentiometric and (1)H NMR studies of complexation of Al(3+) with (-)-epigallocatechin gallate, a major active constituent of green tea. , 2002, Journal of inorganic biochemistry.

[124]  P. Hollman,et al.  Absorption and disposition kinetics of the dietary antioxidant quercetin in man. , 1996, Free radical biology & medicine.

[125]  Paul W. Ryan,et al.  The kinetics and mechanisms of the complex formation and antioxidant behaviour of the polyphenols EGCg and ECG with iron(III). , 2007, Journal of inorganic biochemistry.

[126]  Tianhong Pan,et al.  Potential Therapeutic Properties of Green Tea Polyphenols in Parkinson’s Disease , 2003, Drugs & aging.

[127]  A. Davison,et al.  Effects of metals, ligands and antioxidants on the reaction of oxygen with 1,2,4-benzenetriol. , 1996, Free radical biology & medicine.

[128]  H. Forman,et al.  Oxidants as stimulators of signal transduction. , 1997, Free radical biology & medicine.

[129]  M. Chevion,et al.  Protective effects of tea polyphenols against oxidative damage to red blood cells. , 1997, Biochemical pharmacology.

[130]  D. Giachetti,et al.  Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity , 1997, FEBS letters.

[131]  H. Kikuzaki,et al.  Food components inhibiting recombinant human histidine decarboxylase activity. , 2007, Journal of agricultural and food chemistry.

[132]  P. Dedon,et al.  Cu(II)/H2O2-induced DNA damage is enhanced by packaging of DNA as a nucleosome. , 2001, Chemical research in toxicology.

[133]  Russell K. Feller,et al.  Fe(III), Mn(II), Co(II), and Ni(II) 3,4,5-trihydroxybenzoate (gallate) dihydrates; a new family of hybrid framework materials , 2006 .

[134]  Sten Orrenius,et al.  Mitochondrial oxidative stress: implications for cell death. , 2007, Annual review of pharmacology and toxicology.

[135]  Zhuoxiao Cao,et al.  The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in the presence of copper ions , 2002, Neuroscience Letters.

[136]  B. Seong,et al.  Antiviral effect of catechins in green tea on influenza virus. , 2005, Antiviral research.

[137]  N. Davidson,et al.  Kinetics of the Ferrous Iron-Oxygen Reaction in Acidic Phosphate-Pyrophosphate Solutions , 1958 .

[138]  E. Berenshtein,et al.  The Role of Transition Metal Ions in Free Radical-Mediated Damage , 2002 .

[139]  F. Tomás-Barberán,et al.  Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. , 2000, Journal of agricultural and food chemistry.

[140]  N. Şanlı,et al.  Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic acids in water and acetonitrile–water media , 2003 .

[141]  S. Tannenbaum,et al.  Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents. , 1997, Chemical research in toxicology.

[142]  S. Kawanishi,et al.  Caffeic acid causes metal-dependent damage to cellular and isolated DNA through H2O2 formation. , 1992, Carcinogenesis.

[143]  L. Fay,et al.  Oxidation of Caffeine and Related Methylxanthines in Ascorbate and Polyphenol-Driven Oxidations Fenton-type , 1996 .

[144]  F. Thomas,et al.  Thermodynamic and kinetic studies of the sulfonated derivative of the iron chelator TRENCAM, an analog of enterobactin , 1999 .

[145]  J. Weiß,et al.  Über die Katalyse des Hydroperoxydes , 1932, Naturwissenschaften.

[146]  R. Dean,et al.  Radicals derived from histone hydroperoxides damage nucleobases in RNA and DNA. , 2000, Chemical research in toxicology.

[147]  Dejian Huang,et al.  The chemistry behind antioxidant capacity assays. , 2005, Journal of agricultural and food chemistry.

[148]  Xi Huang Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. , 2003, Mutation research.

[149]  J. Kennedy,et al.  Aluminium(III) and Iron(III) 1,2-Diphenolato Complexes: a Potentiometric Study , 1985 .

[150]  T. Sanderson,et al.  Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms. , 2008, Journal of agricultural and food chemistry.

[151]  A. K. Rodopulo [Oxidation of tartaric acid in wine in the presence of heavy metal salts (activation of oxygen by iron)]. , 1951, Izvestiia Akademii nauk SSSR. Seriia biologicheskaia.

[152]  A. Garg,et al.  Chemosensitization and radiosensitization of tumors by plant polyphenols. , 2005, Antioxidants & redox signaling.

[153]  F. Saura-calixto,et al.  Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. , 2000, Journal of agricultural and food chemistry.

[154]  Y. Kamio,et al.  Regulation of the Intracellular Free Iron Pool by Dpr Provides Oxygen Tolerance to Streptococcus mutans , 2004, Journal of bacteriology.

[155]  K. Yoshinaga,et al.  Kinetic Analysis of the Effect of (−)-Epigallocatechin Gallate on the DNA Scission Induced by Fe(II) , 2002, Bioscience, biotechnology, and biochemistry.

[156]  Y. Hitomi,et al.  Correlation of spin states and spin delocalization with the dioxygen reactivity of catecholatoiron(III) complexes. , 2005, Inorganic chemistry.

[157]  K. Cimanga,et al.  Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. , 1998, Journal of natural products.

[158]  S. Rhee Redox signaling: hydrogen peroxide as intracellular messenger , 1999, Experimental & Molecular Medicine.

[159]  I. Arts,et al.  Catechin contents of foods commonly consumed in The Netherlands. 1. Fruits, vegetables, staple foods, and processed foods. , 2000, Journal of agricultural and food chemistry.

[160]  A. Naganuma,et al.  Metallothionein proteins expression, copper and zinc concentrations, and lipid peroxidation level in a rodent model for amyotrophic lateral sclerosis. , 2007, Toxicology.

[161]  C. Scaccini,et al.  Absorption of phenolic acids in humans after coffee consumption. , 2002, Journal of agricultural and food chemistry.

[162]  P. Bhattacharya,et al.  Effect of substitution on the catecholate ring on ternary complex stability , 1985, Proceedings / Indian Academy of Sciences.

[163]  A. Bendini,et al.  Protective effects of extra virgin olive oil phenolics on oxidative stability in the presence or absence of copper ions. , 2006, Journal of agricultural and food chemistry.

[164]  A. Bast,et al.  Influence of iron chelation on the antioxidant activity of flavonoids. , 1998, Biochemical pharmacology.

[165]  A. Avdeef,et al.  Coordination chemistry of microbial iron transport compounds. 9. Stability constants for catechol models of enterobactin , 1978 .

[166]  J. Freer,et al.  A screening method for detecting iron reducing wood-rot fungi , 2003, Biotechnology Letters.

[167]  A. Bast,et al.  Flavonoids as scavengers of nitric oxide radical. , 1995, Biochemical and biophysical research communications.

[168]  Gary Williamson,et al.  Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. , 2005, The American journal of clinical nutrition.

[169]  E. Bosch,et al.  Determination of dissociation constants of flavonoids by capillary electrophoresis , 2005, Electrophoresis.

[170]  J. Kennedy,et al.  The protonation reactions of catechin, epicatechin and related compounds , 1984 .

[171]  J. Abian,et al.  Complexes of iron with phenolic compounds from soybean nodules and other legume tissues: prooxidant and antioxidant properties. , 1997, Free radical biology & medicine.

[172]  R. Prior,et al.  Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. , 2005, Journal of agricultural and food chemistry.

[173]  H. Fenton,et al.  VII.—The oxidation of organic acids in presence of ferrous iron. Part I , 2022 .

[174]  R. Martins,et al.  Amyloid-β: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-β , 2003, Brain Research Reviews.

[175]  Julia L. Brumaghim,et al.  Kinetics of iron oxidation upon polyphenol binding. , 2010, Dalton transactions.

[176]  H. Powell,et al.  Polyphenol Interactions with Aluminium(III) and Iron(III): their Possible Involvement int he Podzolization Process , 1985 .

[177]  S. Nielsen,et al.  The role of iron and the factors affecting off-color development of polyphenols. , 2003, Journal of agricultural and food chemistry.

[178]  W. Linert,et al.  Anaerobic oxidation of dopamine by iron(III) , 1997 .

[179]  C. Savage-Dunn,et al.  Detection of intracellular iron by its regulatory effect. , 2004, American journal of physiology. Cell physiology.

[180]  G. Lescoat,et al.  Role of flavonoids and iron chelation in antioxidant action. , 1994, Methods in enzymology.

[181]  J. Eaton,et al.  Spontaneous oxygen radical generation by sickle erythrocytes. , 1982, The Journal of clinical investigation.

[182]  G. Ackermann,et al.  Über Eisen(III)-Komplexe mit Phenolen. III. Die Absorptionsspektren und deren Auswertung , 1970 .

[183]  K. Raymond,et al.  Siderophore electrochemistry: relation to intracellular iron release mechanism. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[184]  P. Rouyer‐Fessard,et al.  Effect of excess alpha-hemoglobin chains on cellular and membrane oxidation in model beta-thalassemic erythrocytes. , 1993, The Journal of clinical investigation.

[185]  M. Tabata,et al.  Effects of pH and Metal Ions on Antioxidative Activities of Catechins , 2001, Bioscience, biotechnology and biochemistry.

[186]  W. Bors,et al.  Flavonoids as antioxidants: determination of radical-scavenging efficiencies. , 1990, Methods in enzymology.

[187]  I. Rietjens,et al.  Radical scavenging capacity of wine anthocyanins is strongly pH-dependent. , 2005, Journal of agricultural and food chemistry.

[188]  B. Ames,et al.  Assays of oxidative DNA damage biomarkers 8-oxo-2'-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high-performance liquid chromatography with electrochemical detection. , 1994, Methods in enzymology.

[189]  A. Swaak,et al.  Superoxide dependent iron release from ferritin in inflammatory diseases. , 1988, Free radical biology & medicine.

[190]  John R. Miller,et al.  Model compounds for microbial iron-transport compounds. Part IV. Further solution chemistry and Mössbauer studies on iron(II) and iron(III) catechol complexes , 1983 .

[191]  M. Röcken,et al.  ‘To repair or not to repair – no longer a question’: repair of mitochondrial DNA shielding against age and cancer , 2006, Experimental dermatology.

[192]  M. Sevilla,et al.  Propyl gallate is a superoxide dismutase mimic and protects cultured lens epithelial cells from H2O2 insult. , 2003, Experimental eye research.

[193]  S. Jewett,et al.  Novel method to examine the formation of unstable 2:1 and 3:1 complexes of catecholamines and iron(III)☆ , 1997 .

[194]  B. Sutherland,et al.  Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. , 2006, The Journal of nutritional biochemistry.

[195]  M. Birch-Machin Using mitochondrial DNA as a biosensor of early cancer development , 2005, British Journal of Cancer.

[196]  W. Koppenol The Haber-Weiss cycle – 70 years later , 2001, Redox report : communications in free radical research.

[197]  N. Turro Damage control of DNA in nucleosome core particles: when a histone's loving, protective embrace is just not good enough. , 2002, Chemistry & biology.

[198]  M. Chaur,et al.  Antioxidant and prooxidant effects of polyphenol compounds on copper-mediated DNA damage. , 2011, Journal of inorganic biochemistry.

[199]  Paul W. Ryan,et al.  The kinetics and mechanisms of the reactions of iron(III) with quercetin and morin. , 2008, Journal of inorganic biochemistry.

[200]  J. Kühnau The flavonoids. A class of semi-essential food components: their role in human nutrition. , 1976, World review of nutrition and dietetics.

[201]  I. Cheng,et al.  Stability of ferric complexes with 3-hydroxyflavone (flavonol), 5,7-dihydroxyflavone (chrysin), and 3',4'-dihydroxyflavone. , 2005, Journal of agricultural and food chemistry.

[202]  S. Snyder,et al.  Nitric oxide: a physiologic messenger molecule. , 1994, Annual review of biochemistry.

[203]  S. Srichairatanakool,et al.  Epigallocatechin-3-gallate and epicatechin-3-gallate from green tea decrease plasma non-transferrin bound iron and erythrocyte oxidative stress. , 2007, Medicinal chemistry (Shariqah (United Arab Emirates)).

[204]  A. Potapovich,et al.  Experimental evidence that flavonoid metal complexes may act as mimics of superoxide dismutase. , 2004, Archives of biochemistry and biophysics.

[205]  N. Nilvebrant,et al.  pKa-Values of Guaiacyl and Syringyl Phenols Related to Lignin , 2000 .

[206]  S. Oikawa,et al.  Evaluation for safety of antioxidant chemopreventive agents. , 2005, Antioxidants & redox signaling.

[207]  W. Dröge Free radicals in the physiological control of cell function. , 2002, Physiological reviews.

[208]  Richard M. Noyes,et al.  Mechanisms of Inorganic Reactions. A Study of Metal Complexes in Solution. , 1959 .

[209]  Y. Hara,et al.  Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity , 1996 .

[210]  D. J. Perkins,et al.  Model experiments for the study of iron transfer from transferrin to ferritin. , 2005, European journal of biochemistry.

[211]  L. Zubik,et al.  Phenol antioxidant quantity and quality in foods: cocoa, dark chocolate, and milk chocolate. , 1999, Journal of agricultural and food chemistry.

[212]  Y. Hara,et al.  Antioxidant Potential of Gallocatechins. A Pulse Radiolysis and Laser Photolysis Study , 1995 .

[213]  J. Weststrate,et al.  Bioavailability of catechins from tea: the effect of milk , 1998, European Journal of Clinical Nutrition.

[214]  A. Boschero,et al.  The stimulus-secretion coupling of glucose-induced insulin release , 1978, Pflügers Archiv.

[215]  G. M. Escandar,et al.  Complexing behavior of rutin and quercetin , 1991 .

[216]  M. Valko,et al.  Free radicals, metals and antioxidants in oxidative stress-induced cancer. , 2006, Chemico-biological interactions.

[217]  V. Bohr,et al.  DNA repair, mitochondria, and neurodegeneration , 2007, Neuroscience.

[218]  Arthur E. Martell,et al.  Critical Stability Constants , 2011 .

[219]  Eduardo Medina,et al.  In vitro activity of olive oil polyphenols against Helicobacter pylori. , 2007, Journal of agricultural and food chemistry.

[220]  P. Gao,et al.  Function and mechanism of a low-molecular-weight peptide produced by Gloeophyllum trabeum in biodegradation of cellulose. , 2003, Journal of biotechnology.

[221]  B. Lai,et al.  Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[222]  Reyes Artacho,et al.  Beneficial Effects of Green Tea—A Review , 2006, Journal of the American College of Nutrition.

[223]  井手 友美 Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction , 2001 .

[224]  F. Nanjo,et al.  Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. , 1996, Free radical biology & medicine.

[225]  W. Markesbery,et al.  Oxidative Alterations in Alzheimer's Disease , 1999, Brain pathology.

[226]  W. Pryor,et al.  Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. , 1992, Chemical research in toxicology.

[227]  C. Rensing,et al.  Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli , 2006, Journal of bacteriology.

[228]  H. Ganther,et al.  Selenium: Biochemical Role as a Component of Glutathione Peroxidase , 1973, Science.

[229]  S. M. Hadi,et al.  DNA breakage by tannic acid and Cu(II): sequence specificity of the reaction and involvement of active oxygen species. , 1994, Mutation research.

[230]  S. Mandel,et al.  Neuroprotection and neurorescue against Aβ toxicity and PKC‐dependent release of non‐amyloidogenic soluble precursor protein by green tea polyphenol (‐)‐epigallocatechin‐3‐gallate , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[231]  B. Ames,et al.  Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[232]  M. Imamura,et al.  Differences in Antioxidative Efficiency of Catechins in Various Metal-Induced Lipid Peroxidations in Cultured Hepatocytes , 2001 .

[233]  W. Markesbery,et al.  DNA oxidation in Alzheimer's disease. , 2006, Antioxidants & redox signaling.

[234]  S. Mandel,et al.  Multifunctional Activities of Green Tea Catechins in Neuroprotection , 2005, Neurosignals.

[235]  F. Guglielmi,et al.  Antioxidant and radical scavenging properties in vitro of polyphenolic extracts from red wine , 2001, European journal of nutrition.

[236]  A. M. Posner The kinetics of autoxidation of ferrous ions in concentrated HCl solutions , 1953 .

[237]  P. Das,et al.  Effect of organic acids and polyphenols on in vitro available iron from foods , 2003 .

[238]  T. Mukherjee,et al.  Radical scavenging and catalytic activity of metal-phenolic complexes. , 2005, The journal of physical chemistry. B.

[239]  Y Hanasaki,et al.  The correlation between active oxygens scavenging and antioxidative effects of flavonoids. , 1994, Free radical biology & medicine.

[240]  Thomas M. Garrett,et al.  Macrocyclic catechol-containing ligands , 1988 .

[241]  B. Casto,et al.  Chemoprevention by Fruit Phenolic Compounds , 2004 .

[242]  G. Dodin,et al.  "In vitro" protection of DNA from Fenton reaction by plant polyphenol verbascoside. , 2005, Biochimica et biophysica acta.

[243]  L. Cipak,et al.  Study of antioxidant effect of apigenin, luteolin and quercetin by DNA protective method. , 2001, Neoplasma.

[244]  Amit Jain,et al.  Screening methods of antioxidant activity: An overview , 2007 .

[245]  S. Linn,et al.  DNA damage and oxygen radical toxicity. , 1988, Science.

[246]  S. Mertens-Talcott,et al.  Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers. , 2006, Journal of agricultural and food chemistry.

[247]  M. Dachá,et al.  Quercetin prevents DNA single strand breakage and cytotoxicity caused by tert-butylhydroperoxide: free radical scavenging versus iron chelating mechanism. , 1998, Free radical biology & medicine.

[248]  E. Parisi,et al.  Changes in zinc, copper and metallothionein contents during oocyte growth and early development of the teleost Danio rerio (zebrafish). , 2003, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[249]  L. Korkina,et al.  Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals. , 2001, Biochemical pharmacology.

[250]  K. Storey,et al.  Deoxyribose degradation catalyzed by Fe(III)-EDTA: kinetic aspects and potential usefulness for submicromolar iron measurements , 1994, Molecular and Cellular Biochemistry.

[251]  B. Halliwell,et al.  Role of Free Radicals in the Neurodegenerative Diseases , 2001, Drugs & aging.

[252]  D. Wemmer,et al.  Localization of Fe2+ at an RTGR sequence within a DNA duplex explains preferential cleavage by Fe2+ and H2O2 , 2001 .

[253]  E. Matuschek,et al.  Oxidation of polyphenols and the effect on In vitro iron accessibility in a model food system , 2002 .

[254]  Q. Guo,et al.  Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. , 1996, Biochimica et biophysica acta.

[255]  G. Mugesh,et al.  Structure–Activity Correlation between Natural Glutathione Peroxidase (GPx) and Mimics: A Biomimetic Concept for the Design and Synthesis of More Efficient GPx Mimics , 2001 .

[256]  G. Oboh,et al.  Polyphenols in red pepper [Capsicum annuum var. aviculare (Tepin)] and their protective effect on some pro-oxidants induced lipid peroxidation in brain and liver , 2007 .

[257]  G. Cole,et al.  The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse , 2001, The Journal of Neuroscience.

[258]  L. Que,et al.  STRUCTURE OF A MONONUCLEAR IRON(II)-CATECHOLATE COMPLEX AND ITS RELEVANCE TO THE EXTRADIOL-CLEAVING CATECHOL DIOXYGENASES , 1995 .

[259]  Gary Williamson,et al.  Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. , 2005, The American journal of clinical nutrition.

[260]  M. Periago,et al.  Phenolic-rich juice prevents DNA single-strand breakage and cytotoxicity caused by tert-butylhydroperoxide in U937 cells: the role of iron chelation. , 2007, The Journal of nutritional biochemistry.

[261]  W. Berger,et al.  Green tea extract and (−)‐epigallocatechin‐3‐gallate, the major tea catechin, exert oxidant but lack antioxidant activities , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[262]  N. Sugihara,et al.  The contribution of the pyrogallol moiety to the superoxide radical scavenging activity of flavonoids. , 2002, Biological & pharmaceutical bulletin.

[263]  E. Mentasti,et al.  Reactions between iron(III) and catechol (o-dihydroxybenzene). part I. Equilibria and kinetics of complex formation in aqueous acid solution , 1973 .

[264]  T. Schultz,et al.  Metal chelation studies relevant to wood preservation.1. Complexation of propyl gallate with Fe2+ , 2005 .

[265]  J. Imlay,et al.  Copyright � 1995, American Society for Microbiology Superoxide and the Production of Oxidative DNA Damage , 1995 .

[266]  T. Tsuruo,et al.  Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo. , 2003, Cancer research.

[267]  Chung S. Yang,et al.  Mechanisms of cancer prevention by tea constituents. , 2003, The Journal of nutrition.

[268]  J. H. Parish,et al.  Strand scission in DNA induced by quercetin and Cu(II): role of Cu(I) and oxygen free radicals. , 1989, Carcinogenesis.

[269]  Ya Ke,et al.  Iron misregulation in the brain: a primary cause of neurodegenerative disorders , 2003, The Lancet Neurology.

[270]  N. Andrews Probing the iron pool. Focus on "Detection of intracellular iron by its regulatory effect". , 2004, American journal of physiology. Cell physiology.

[271]  L. Fay,et al.  Oxidation of caffeine and related methylxanthines in ascorbate and polyphenol-driven Fenton-type oxidations. , 1996, Free radical research.

[272]  R. Thomas. Myers Hard and soft acids and bases , 2002 .

[273]  Ludmil Benov How superoxide radical damages the cell , 2005, Protoplasma.

[274]  P. Bose,et al.  Phenol antioxidant quantity and quality in foods: fruits. , 2001, Journal of agricultural and food chemistry.

[275]  A Jacobs,et al.  Low molecular weight intracellular iron transport compounds. , 1977, Blood.

[276]  J. Strain,et al.  Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. , 2004, The American journal of clinical nutrition.

[277]  L. Zubik,et al.  Phenol antioxidant quantity and quality in foods : Vegetables , 1998 .

[278]  C. Colton,et al.  Reactive Oxygen Species in Biological Systems , 2013, Springer US.

[279]  John Hardy,et al.  The A53T α-Synuclein Mutation Increases Iron-Dependent Aggregation and Toxicity , 2000, The Journal of Neuroscience.

[280]  G. R. Fisher,et al.  Free radical formation and DNA strand breakage during metabolism of diaziquone by NAD(P)H quinone-acceptor oxidoreductase (DT-diaphorase) and NADPH cytochrome c reductase. , 1991, Free radical biology & medicine.

[281]  A. Puppo Effect of flavonoids on hydroxyl radical formation by Fenton-type reactions; influence of the iron chelator , 1992 .

[282]  M. Kadiiska,et al.  In vivo copper-mediated free radical production: an ESR spin-trapping study. , 2002, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[283]  R. Crawford,et al.  De novo synthesis of 4,5-dimethoxycatechol and 2, 5-dimethoxyhydroquinone by the brown rot fungus Gloeophyllum trabeum. , 1999, Applied and environmental microbiology.

[284]  R. Meneghini,et al.  Iron is the intracellular metal involved in the production of DNA damage by oxygen radicals. , 1991, Mutation research.

[285]  D. Ecker,et al.  Coordination Chemistry of Microbial Iron Transport Compounds. Part 34. , 1986 .

[286]  D. Allsop,et al.  alpha-Synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. , 2001, Free radical biology & medicine.

[287]  A. Aro,et al.  Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables , 2002, European Journal of Clinical Nutrition.

[288]  A. Mayer Polyphenol oxidases in plants and fungi: going places? A review. , 2006, Phytochemistry.

[289]  J. Vinson Flavonoids in foods as in vitro and in vivo antioxidants. , 1998, Advances in experimental medicine and biology.

[290]  R. Hider,et al.  Metal Chelation of Polyphenols , 2001 .

[291]  H. Schulman,et al.  Polyphenol tannic acid inhibits hydroxyl radical formation from Fenton reaction by complexing ferrous ions. , 1999, Biochimica et biophysica acta.

[292]  I. Bremner Manifestations of copper excess. , 1998, The American journal of clinical nutrition.