Journal of the American Oil Chemists' Society

, Volume 75, Issue 2, pp 199–212 | Cite as

Free radicals, oxidative stress, and antioxidants in human health and disease

  • Okezie I. Aruoma
Article

Abstract

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body. Free-radical mechanisms have been implicated in the pathology of several human diseases, including cancer, atherosclerosis, malaria, and rheumatoid arthritis and neurodegenerative diseases. For example, the superoxide radical (O2·−) and hydrogen peroxide (H2O2) are known to be generated in the brain and nervous system in vivo, and several areas of the human brain are rich in iron, which appears to be easily mobilizable in a form that can stimulate free-radical reactions. Antioxidant defenses to remove O2·− and H2O2 exist. Superoxide dismutases (SOD) remove O2·− by greatly accelerating its conversion to H2O2. Catalases in peroxisomes convert H2O2 into water and O2 and help to dispose of H2O2 generated by the action of the oxidase enzymes that are located in these organelles. Other important H2O2-removing enzymes in human cells are the glutathione peroxidases. When produced in excess, ROS can cause tissue injury. However, tissue injury can itself cause ROS generation (e.g., by causing activation of phagocytes or releasing transition metal ions from damaged cells), which may (or may not, depending on the situation) contribute to a worsening of the injury. Assessment of oxidative damage to biomolecules by means of emerging technologies based on products of oxidative damage to DNA (e.g., 8-hydroxydeoxyguanosine), lipids (e.g., isoprostanes), and proteins (altered amino acids) would not only advance our understanding of the underlying mechanisms but also facilitate supplementation and intervention studies designed and conducted to test antioxidant efficacy in human health and disease.

Key words

Antioxidants atherosclerosis DNA damage flavonoids free radicals 8-hydroxydeoxyguanosine isoprostanes lipid peroxidation oxidative protein damage oxidative stress phytochemicals 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gomberg, M., An Incidence of Trivalent Carbon Trimethylphenyl, J. Am. Chem. Soc. 22:757–771 (1900).CrossRefGoogle Scholar
  2. 2.
    Hey, D.H., and W.A. Waters, Some Organic Reactions Involving the Occurrence of Free Radicals in Solution, Chem. Rev. 21:169–208 (1937).CrossRefGoogle Scholar
  3. 3.
    Cadogan, J.I.G., Principles of Free Radical Chemistry, The Chemical Society, London, 1973.Google Scholar
  4. 4.
    Weiss, J., Investigations of the Radical HO2 in Solution, Trans. Faraday Soc. 31:668–681 (1935).CrossRefGoogle Scholar
  5. 5.
    Perkins, M.J., Radical Chemistry, Ellis Horwood, London 1996.Google Scholar
  6. 6.
    Moad, G., and D.H. Solomon, The Chemistry of Free Radical Polymerization, Pergamon, Oxford, 1995.Google Scholar
  7. 7.
    Waters, W.A., A Chemical Interpretation of the Mechanism of Oxidation by Dehydrogenase Enzymes, Trans. Faraday Soc. 39:140–151 (1943).CrossRefGoogle Scholar
  8. 8.
    Gerschman, R., D.L. Gilbert, S.W. Nye, P. Dwyer, and W.O. Fenn, Oxygen Poisoning and X-Irradiation: A Mechanism in Common, Science 119:623–626 (1954).PubMedCrossRefADSGoogle Scholar
  9. 9.
    McCord, J.M., and I. Fridovich, Superoxide Dismutase. An Enzymatic Function for Erythrocuprein (Hemocuprein), J. Biol. Chem. 224:6049–6055 (1969).Google Scholar
  10. 10.
    Michelson, A.M., J.M. McCord, and I. Fridovich, Superoxide and Superoxide Dismutases, Academic Press, London, 1977.Google Scholar
  11. 11.
    Aruoma, O.I., Free Radicals and Foods, Chem. Br. 29:210–214 (1993).Google Scholar
  12. 12.
    Porter, W.L., Paradoxical Behaviour of Antioxidants in Food and Biological Systems, Toxicol. Ind. Health 9:93–122 (1993).PubMedGoogle Scholar
  13. 13.
    Hudson, B.J.F., Food Antioxidant, Elsevier Applied Science London.Google Scholar
  14. 14.
    Frankel, E.N., Lipid Oxidation, Prog. Lipid Res. 19:1–22 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    Papas, A.M., Oil-Soluble Antioxidants in Foods, Toxicol. Ind. Health 9:123–149 (1993).PubMedGoogle Scholar
  16. 16.
    Löliger, R., The Use of Antioxidants in Food, in Free Radicals and Food Additives, edited by O.I. Aruoma and B. Halliwell, Tayler & Francis, London, 1991, pp. 121–150.Google Scholar
  17. 17.
    Diplock, A.T., Antioxidant Nutrients and Disease Prevention: An Overview, Am. J. Clin. Nutr. 53:189S–193S.Google Scholar
  18. 18.
    Block, G., B. Pattersen, and A. Subar, Fruit, Vegetables and Cancer Prevention: A Review of the Epidemiological Evidence, Nutr. Cancer 18:1–29 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    Aruoma, O.I., Characterization of Drugs as Antioxidant Prophylactics, Free Radical Biol. Med. 20:675–705 (1996).CrossRefGoogle Scholar
  20. 20.
    Duthie, S.J., A. Ma, M.A. Ross, and A.R. Collins, Antioxidant Supplementation Decreases Oxidative DNA Damage in Human Lymphocytes, Cancer Res. 56:1291–1295 (1996).PubMedGoogle Scholar
  21. 21.
    Pezzuto, J.M., Plant-Derived Anticancer Agents, Biochem. Pharmacol. 53:121–133 (1997).PubMedCrossRefGoogle Scholar
  22. 22.
    Pryor, W.A., Free Radical Biology: Xenobiotics, Cancer, and Aging, Ann. N.Y. Acad. Sci. 393:1–22 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    Southorn, P.A., and G. Powis, Free Radicals in Medicine II. Involvement in Human Disease, Mayo Clin. Proc. 63:390–408 (1988).PubMedGoogle Scholar
  24. 24.
    Halliwell, B., and J M.C. Gutteridge, Free Radicals in Biology and Medicine, Clarendon Press Oxford, 1989.Google Scholar
  25. 25.
    Aruoma, O.I., Free Radicals in Tropical Diseases, Harwood Academic Publishers, London, 1991.Google Scholar
  26. 26.
    Babior, B.M., Oxidants from Phagocytes: Agents of Defense and Destruction, Blood 64:959–966 (1984).PubMedGoogle Scholar
  27. 27.
    Klebanoff, S.J., Oxygen Metabolism and the Toxic Properties of Phagocytes, Ann. Intern. Med. 93:480–489 (1980).PubMedGoogle Scholar
  28. 28.
    Weiss, S.J., Tissue Destruction by Neutrophils, New Engl. J. Med. 320:365–376 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    Del-Maestro, R.F., An Approach to Free Radicals in Medicine and Biology, Acta Physiol. Scand. suppl. 492:153–168 (1980).PubMedGoogle Scholar
  30. 30.
    For a collection of review articles, see Oxygen Radicals and Lung Injury, Environ. Health Perspect. 102 (suppl 10) 5–213 (1994).Google Scholar
  31. 31.
    Orrenius, S., D.J. McConkey, G. Bellomo, and P. Nicotera, Role of Ca2+ in Toxic Cell Killing, Trends Pharmacol. Sci. 10:281–285 (1989).PubMedCrossRefGoogle Scholar
  32. 32.
    Bast, A., Oxidative Stress and Calcium Homeostasis, in DNA and Free Radicals, edited by B. Halliwell and O.I. Aruoma, Ellis Horwood, London, 1993, pp. 95–108.Google Scholar
  33. 33.
    Stokinger, H.E., Ozone Toxicology, Arch. Environ. Health 10: 719–731 (1965).PubMedGoogle Scholar
  34. 34.
    Mustafa, M.G., Biochemical Basis of Ozone Toxicity, Free Radical Biol. Med. 9:245–265 (1990).CrossRefGoogle Scholar
  35. 35.
    Pryor, W.A., Mechanism of Radical Formation from Reactions of Ozone with Target Molecules in the Lung, Ibid.:451–465 (1994).CrossRefGoogle Scholar
  36. 36.
    Kanofsky, J.R., and P. Sima, Singlet Oxygen Production from the Reactions of Ozone with Biological Molecules, J. Biol. Chem. 266:9039–9042 (1991).PubMedGoogle Scholar
  37. 37.
    Palmer, R.M.J., D.S. Ashton, and S. Moncada, Vascular Endothelium Cell Synthesize Nitric Oxide from l-Arginine, Nature 333:664–666 (1988).PubMedCrossRefADSGoogle Scholar
  38. 38.
    Ignarro, L.J., G.M. Buga, K.S. Wood, R.E. Byrns, and G. Chandhuri, Endothelium-Derived Relaxing Factor Produced and Released from Artery and Vein Is Nitric Oxide, Proc. Natl. Acad. Sci. USA 84:9265–9269 (1987).PubMedCrossRefADSGoogle Scholar
  39. 39.
    Sneddon, J.W., and J.R. Vane, Endothelium-Derived Relaxing Factor Reduces Platelet Adhesion to Bovine Endothelium Cells, Ibid.:1341–1344 (1988).Google Scholar
  40. 40.
    Gaston, B., J.M. Drazen, J. Lescalzo, and J.S. Stamler, The Biology of Nitrogen Oxide in the Airways, Am. J. Respir. Crit. Care Med. 149:538–551 (1994).PubMedGoogle Scholar
  41. 41.
    Anggärd, E., Nitric Oxide: Mediator, Murderer and Medicine, Lancet 343:1199–1206 (1994).PubMedCrossRefGoogle Scholar
  42. 42.
    Rubbo, H., V. Darley-Usmar, and B.A. Freeman, Nitric Oxide Regulation of Tissue Free Radical Injury, Chem. Res. Toxicol. 9:809–820 (1996).PubMedCrossRefGoogle Scholar
  43. 43.
    Lancaster, J., ed., The Biological Chemistry of Nitric Oxide, Academic Press, New York, 1995.Google Scholar
  44. 44.
    Sessa, W.C., K. Pritchard, N. Seyedi, J. Wang, and T.H. Hintze, Chronic Exercise in Dogs Increases Coronary Vascular Nitric Oxide Production and Endothelial Cell Nitric Oxide Synthase Gene Expression, Circ. Res. 74:349–353 (1994).PubMedGoogle Scholar
  45. 45.
    de Rojas-Walker, T., S. Tamir, J. Hong, J.S. Wishnok, and S.R. Tannenbaum, Nitric Oxide Induces Oxidative Damage in Addition to Deamination in Macrophage DNA. Chem. Res. Toxicol. 8:473–477 (1995).CrossRefGoogle Scholar
  46. 46.
    Douki, H., and J. Cadet, Peroxynitrite Mediated Oxidation of Purine Bases of Nucleosides and Isolated DNA, Free Rad. Res. 24:369–380 (1996).Google Scholar
  47. 47.
    Uppu, R.M., R. Cueto, G.L. Squadrito, M.G. Salgo, and W.A. Pryor, Reactions of Peroxynitrite with 2′-Deoxyguanosine, 7,8-dihydro-8-oxo-2′-deoxyguanosine, and Calf-thymus DNA, Free Radical Biol. Med. 21:407–411 (1996).CrossRefGoogle Scholar
  48. 48.
    Merchant, K., H. Chen, T.C. Gonzalez, L.K. Keefer, and B.R. Shaw, Deamination of Single-Stranded DNA Cytosine Residues in Aerobic Nitric Oxide Solution at Micromolar Total NO Exposures, Chem. Res. Toxicol. 9:891–896 (1996).PubMedCrossRefGoogle Scholar
  49. 49.
    Douki, T., J. Cadet, and B.N. Ames, An Adduct Between Peroxynitrite and 2′-Deoxyguanosine: 4,5-Dihydro-5-hydroxy-4-(nitrosooxy)-2′-deoxyguanosine, Ibid.:3–7 (1996).PubMedCrossRefGoogle Scholar
  50. 50.
    Yermilov, V., J. Rubio, and H. Ohshima, Formation of 8-Ni-troguanine in DNA Treated with Peroxynitrite in vitro and Its Rapid Removal from DNA by Depurination, FEBS Lett. 376:207–210 (1995).PubMedCrossRefGoogle Scholar
  51. 51.
    Spencer, J.P.E., A. Jenner, O.I. Aruoma, C.E. Cross, and B. Halliwell, Base Modification and Strand Breakage in Isolated Calf Thymus DNA and in DNA from Human Skin Epidermal Keratinocytes Exposed to Peroxynitrite or 3-Morpholinosyd-nonimine, Chem. Res. Toxicol. 9:1152–1158 (1996).PubMedCrossRefGoogle Scholar
  52. 52.
    Salgo, M.G., K. Stone, G.L. Squadrito, J.R. Battista, and W.A. Pryor, Peroxynitrite Causes DNA Nicks in Plasmid pBR322, Biochem. Biophys. Res. Commun. 210:1026–1030 (1995).CrossRefGoogle Scholar
  53. 53.
    Huie, R.E., and S. Padmaja, The Reaction of NO with Superoxide, Free Radical Res. Commun. 18:195–199 (1993).Google Scholar
  54. 54.
    van der Vliet, A., D. Smith, C.A. O’Neill, H. Kaur, V. Darley-Usmar, C.E. Cross, and B. Halliwell, Interactions of Peroxynitrite with Human Plasma and Its Constituents: Oxidative Damage and Antioxidant Depletion, Biochem. J. 303:295–301 (1994).PubMedGoogle Scholar
  55. 55.
    Gatti, R.M., O. Augusto, J.K. Kwee, and S. Giorgio, Leish-manicidal Activity of Peroxynitrite, Redox Rep. 1:261–265 (1995).Google Scholar
  56. 56.
    Watts, B.P., M. Barnard, and J.F. Turrens, Peroxynitrite-Dependment Chemuliminescence of Amino Acids, Proteins and Intact Cells, Arch. Biochem. Biophys. 317:324–330 (1995).PubMedCrossRefGoogle Scholar
  57. 57.
    Zhu, L., C. Gunn, and J.S. Beckman, Bactericidal Activity of Peroxynitrite, Ibid.:452–457 (1992).PubMedCrossRefGoogle Scholar
  58. 58.
    Radi, R., J.S. Beckman, K.M. Bush, and B.A. Freeman, Peroxynitrite Oxidation of Sulfhydryls. The Cytotoxic Potential of Superoxide and Nitric Oxide, J. Biol. Chem. 266:4244–4250 (1991).PubMedGoogle Scholar
  59. 59.
    Tarpey, M.M., J.S. Beckman, H. Ischiropolous, J.Z. Gore, and T.A. Brock, Peroxynitrite Stimulates Vascular Smooth Muscle Cell Cyclic GMP Synthesis, FEBS Lett. 364:314–318 (1995).PubMedCrossRefGoogle Scholar
  60. 60.
    Kalyanaraman, B., V. Darley-Usmar, A. Struck, N. Hogg, and S. Parathasarathy, Role of Apolipoprotein-Derived Radical and α-Tocopheroxyl Radical in Peroxidase-Dependent Oxidation of Low Density Lipoprotein, J. Lipid Res. 36:1037–1045 (1995).PubMedGoogle Scholar
  61. 61.
    Pryor, W.A., and G.L. Squadrito, The Chemistry of Peroxynitrite: A Product from the Reaction of Nitric Oxide with Superoxide, Lung Cell. Mol. Physiol. 12:L699-L722 (1995).Google Scholar
  62. 62.
    Graham, A., N. Hogg, B. Kalyanaraman, V. O’Leary, V. Darley-Usmar, and S. Moncada, Peroxynitrite Modification of Low-Density Lipoprotein Leads to Recognition by the Macrophage Scavenger Receptor, FEBS Lett. 330:181–185 (1993).PubMedCrossRefGoogle Scholar
  63. 63.
    Ischiropoulos, H., and A.B. Al-Mehdi, Peroxynitrite Mediated Oxidative Protein Modifications, Ibid.:279–282 (1995).PubMedCrossRefGoogle Scholar
  64. 64.
    Esterbauer, H., J. Gebicki, H. Puhl, and G. Juergens, The Role of Lipid Peroxidation and Antioxidants on Oxidative Modification of LDL, Free Radical Biol. Med. 13:341–390 (1992).CrossRefGoogle Scholar
  65. 65.
    Cerruti, P.A., Pro-oxidant States and Tumor Activation, Science 227:375–381 (1985).CrossRefADSGoogle Scholar
  66. 66.
    Cheeseman, K.H., Lipid Peroxidation and Cancer, in DNA and Free Radicals, edited by B. Halliwell and O.I. Aruoma, pp. 109–144, Ellis Horwood, London, 1993.Google Scholar
  67. 67.
    Morrow, J.D., K.E. Hill, R.F. Burk, T.M. Mannour, K.F. Badr, and L.J. Roberts, A Series of Prostaglandin F2 Like Compounds Are Produced in vivo by Humans by a Non-cyclooxygenase, Free Radical Catalyzed Mechanism, Proc. Natl. Acad. Sci. USA 87:9383–9387 (1990).PubMedCrossRefADSGoogle Scholar
  68. 68.
    Morrow, J.D., and L.J. Roberts, The Isoprostanes: Current Knowledge and Directions for Future Research, Biochem. Pharmacol. 51:1–9 (1996).PubMedCrossRefGoogle Scholar
  69. 69.
    Esterbauer, H., The Chemistry of Oxidation of Lipoproteins, in Oxidative Stress, Lipoproteins and Cardiovascular Dysfunction, edited by C. Rice-Evans and K.R. Bruckdorfer, Portland Press, London, 1995, pp. 55–79.Google Scholar
  70. 70.
    Kalyanaraman, B., and P.G. Sohnle, Generation of Free Radical Intermediates from Foreign Compounds by Neutrophil-Derived Oxidants, J. Clin. Invest. 75:1618–1622 (1985).PubMedGoogle Scholar
  71. 71.
    Carr, A.C., J.J.M. van den Berg, and C.C. Winterbourn, Chlorination of Cholesterol in Cell Membranes by Hypochlorous Acid, Arch. Biochem. Biophys. 332:63–69 (1996).PubMedCrossRefGoogle Scholar
  72. 72.
    Travis, J., and G.S. Salvesen, Human Plasma Proteinase Inhibitors, Annu. Rev. Biochem. 52:655–709 (1983).PubMedCrossRefGoogle Scholar
  73. 73.
    Dennis, W.H., V.P. Oliveieri, and C.W. Kruse, The Reaction of Nucleotides with Aqueous Hypochlorous Acid, Water Res. 13:357–362 (1979).CrossRefGoogle Scholar
  74. 74.
    Gould, J.P., and T.R. Hay, The Nature of the Reactions Between Chlorine and Purine and Pyrimidine Bases: Products and Kinetics, Wat. Res. Tech. 14:629–640 (1982).Google Scholar
  75. 75.
    Kozumbo, W.J., S. Agarwal, and H.S. Koren, Breakage and Binding of DNA by Reaction Products of Hypochlorous Acid with Aniline, 1-Naphthylamine or 1-Naphthol, Toxicol. Appl. Pharmacol. 115:107–115 (1992).PubMedCrossRefGoogle Scholar
  76. 76.
    Aruoma, O.I., B. Halliwell, R. Aeschbach, and J. Löliger, Antioxidant and Pro-oxidant Properties of Active Rosemary Constituents: Carnosol and Carnosic Acid, Xenobiotica 22:257–268 (1992).PubMedCrossRefGoogle Scholar
  77. 77.
    Aruoma, O.I., A. Murcia, J. Butler, and B. Halliwell, Evaluation of the Antioxidant Actions of Gallic Acid and Its Derivatives, J. Food Chem. 41:1880–1885 (1993).CrossRefGoogle Scholar
  78. 78.
    Aruoma, O.I., Nutrition and Health Aspects of Free Radicals and Antioxidants, Food Chem. Toxicol. 32:671–683 (1994).PubMedCrossRefGoogle Scholar
  79. 79.
    Fridovich, I., Superoxide Dismutases. An Adaptation to the Paramagnetic Gas, J. Biol. Chem. 264:7761–7764 (1989).PubMedGoogle Scholar
  80. 80.
    Aruoma, O.I., B. Halliwell, E. Gajeswki, and M. Dizdaroglu, Copper-Ion Dependent Damage to the Bases in DNA in the Presence of Hydrogen Peroxide, Biochem. J. 273:601–604 (1991).PubMedGoogle Scholar
  81. 81.
    Aruoma, O.I., and B. Halliwell, Superoxide-Dependent and Ascorbate-Dependent Formation of Hydroxyl Radicals from Hydrogen Peroxide in the Presence of Iron: Are Lactoferrin and Transferrin Promoters of Hydroxyl Radical Generation, Ibid.:273–278 (1987).PubMedGoogle Scholar
  82. 82.
    Halliwell, B., and J.M.C. Gutteridge, Role of Free Radicals and Catalytic Metal Ions in Human Disease: An Overview, Methods Enzymol. 186:1–85 (1990).PubMedGoogle Scholar
  83. 83.
    Chevion, M., Y. Liang, R. Har-El, E. Berenshtein, G. Uretzky, and N. Kitrossky, Copper and Iron Are Mobilized Following Myocardial Ischemia: Possible Productive Criteria for Tissue Injury, Proc. Natl. Acad. Sci. USA 90:1102–1106 (1993).PubMedCrossRefADSGoogle Scholar
  84. 84.
    Ramos, C.L., S. Pou, B.E. Britigan, M.S. Cohen, and G.M. Rosen, Spin Trapping Evidence for Myeloperoxidase-Dependent Hydroxyl Radical Formation by Human Neutrophils and Monocytes, J. Biol. Chem. 267:8307–8312 (1992).PubMedGoogle Scholar
  85. 85.
    Ramos, C.L., S. Pou, and G.M. Rosen, Effect of Antiinflammatory Drugs on Myeloperoxidase-Dependent Hydroxy Radical Generation by Human Neutrophils, Biochem. Pharmacol. 49:1079–1084 (1995).PubMedCrossRefGoogle Scholar
  86. 86.
    Olanow, C.W., P. Jenner, and M. Youdim, Neurodegeneration and Neuroprotection in Parkinson’s Disease, Academic Press, London, 1996.Google Scholar
  87. 87.
    Moncada, S., and A. Higgs, The l-Arginine-Nitric Oxide Pathway, New Engl. J. Med. 329:2002–2012 (1993).PubMedCrossRefGoogle Scholar
  88. 88.
    Ames, B.N., M.K. Shigenaga, and T.M. Hagen, Oxidants, Antioxidants, and the Degenerative Disease of Aging, Proc. Natl. Acad. Sci. USA 90:7915–7922 (1993).PubMedCrossRefADSGoogle Scholar
  89. 89.
    Ganguly, P.K., Antioxidant Therapy in Congestive Heart Failure: Is There Any Advantage? J. Intern. Med. 229:205–208 (1991).PubMedCrossRefGoogle Scholar
  90. 90.
    Frei, B. (ed.), Natural Antioxidants in Human Health and Disease, Academic Press, New York, 1994.Google Scholar
  91. 91.
    McCord, J.M., Human Disease, Free Radicals and the Oxidant/Antioxidant Balance, Clin. Biochem. 26:351–357 (1993).PubMedMathSciNetCrossRefGoogle Scholar
  92. 92.
    Clemens, M.R., Antioxidant Therapy in Haematological Disorders, Adv. Exp. Biol. Med. 264:423–433 (1990).Google Scholar
  93. 93.
    Haumann, B.F., Antioxidants: Health Implications, INFORM 5:242–252 (1994).Google Scholar
  94. 94.
    Ong, A.S.H., and L. Packer (eds.), Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications, Birkhauser, Basel, 1992.Google Scholar
  95. 95.
    Gutteridge, J.M.C., and B. Halliwell, Antioxidants in Nutrition, Health and Disease, Oxford University Press, Oxford, 1995.Google Scholar
  96. 96.
    Kumpulainen, J.T., and J.T. Salonen (eds.), Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention, Royal Society of Chemistry, London, 1996.Google Scholar
  97. 97.
    Halliwell, B., Antioxidants in Human Health and Disease, Annu. Rev. Nutr. 16:33–50 (1996).PubMedCrossRefGoogle Scholar
  98. 98.
    Sies, H., Antioxidants in Disease Mechanisms and Therapy, Academic Press, London, Vol. 38, Advances in Pharmacology Series, 1996.Google Scholar
  99. 99.
    Stampfer, M.J., C.H. Hennekens., J.E. Manson, G.A. Colditz, B. Rosner, and W.C. Willett, Vitamin E Consumption and the Associated Risk of Coronary Disease in Women, New Engl. J. Med. 328:1444–1449 (1993).PubMedCrossRefGoogle Scholar
  100. 100.
    Knekt, P., A. Reunanen, R. Järvinen, R. Seppänen, M. Heliövaara, and A. Aromaa, Antioxidant Vitamin Intake and Coronary Mortality in a Longitudinal Population Study, Am. J. Epidemiol. 139:1180–1189 (1994).PubMedGoogle Scholar
  101. 101.
    Hertog, M.G.L., E.J.M. Feskens, P.C. Hollman, M.B. Katan, and D. Kromhout, Dietary Antioxidant Flavonoids and Risk of Coronary Heart Disease: The Zutphen Elderly Study, Lancet 342:1007–1011 (1993).PubMedCrossRefGoogle Scholar
  102. 102.
    Gey, K.F., Long Term Adequacy of All Major Antioxidants, Presumably in Synergy with Other Vegetable-Derived Nutrients May Help to Prevent Early Stages of Cardiovascular Disease and Cancer Respectively, Int. J. Vitamin Nutr. Res. 65:65–69 (1995).Google Scholar
  103. 103.
    Manson, J.E., M.J. Stampfer, W.C. Willett, G.A. Colditz, P.E. Speizer, and C.H. Hennekens, Consumption of Antioxidant Vitamins and Incidence of Stroke in Women, Am. J. Epidemiol. 138:603 (1993).Google Scholar
  104. 104.
    Gridley, G., J.K. McLaughlin, G. Block, W.J. Blot, M. Gluch, and J.F. Fraumeni, Vitamin Supplement Use and Reduced Risk of Oral and Pharyngeal Cancer, Ibid.:1083–1092 (1992).PubMedGoogle Scholar
  105. 105.
    Hankinson, S.E., J.J. Stampfer, J.M. Seddon, G.A. Colditz, B. Rosner, F.E. Speizer, and W.C. Willett, Nutrient Intake and Cataract Extraction in Women: A Prospective Study, Brit. Med. J. 305:335–339 (1992).PubMedGoogle Scholar
  106. 106.
    Gey, K.F., H.B. Stähelin, and M. Eichholzer, Poor Plasma Status of Carotene and Vitamin C Is Associated with Higher Mortality from Ischemic Heart Disease and Stroke: Basel Prospective Study, Clin. Invest. 71:3–6 (1993).CrossRefGoogle Scholar
  107. 107.
    Jialal, I., and S.M. Grundy, Effect of Dietary Supplementation with Alpha-Tocopherol on the Oxidative Modification of Low Density Lipoprotein, J. Lipid Res. 33:899–906 (1992).PubMedGoogle Scholar
  108. 108.
    Blot, W.J., J.-Y. Li, P.R. Taylor, W. Guo, S. Dawsey, G.-Q. Wang, C.S. Yang, S.-F. Zheng, M. Gail, G.-Y. Li, Y. Yu, B.-Q. Liu, J. Tangrea, Y.-H. Sun, F. Liu, J.F. Fraumeni, Y.-H. Zhang, and B. Li, Nutrition Intervention Trials in Linxian, China, Supplementation with Specific Vitamin/Mineral Combinations, Cancer Incidence and Disease Specific Mortality in the General Population, J. Natl. Cancer Inst. 85:1483–1492 (1993).PubMedCrossRefGoogle Scholar
  109. 109.
    West, S., S. Vitale, J. Hallfrisch, B. Munoz, D. Muller, S. Bressler, and N.M. Bressler, Are Antioxidants or Supplements Protective for Age Related Macular Degeneration, Arch. Ophthalmol. 112:222–227 (1994).PubMedGoogle Scholar
  110. 110.
    Greenberg, E.R., J.A. Baron, T.D. Tostesen, D.H. Freeman, G.J. Beck, J.H. Bond, T.A. Colacchio, J.A. Collier, H.D. Frankl, R.W. Haile, J.S. Mandel, D.W. Nierenberg, R. Rothistein, D.C. Snozer, N.M. Stevens, R.W. Summers, and R.U. van Stolk, A Clinical Trial of Antioxidant Vitamins to Prevent Colorectal Adenoma, New Engl. J. Med. 331:141–147 (1994).PubMedCrossRefGoogle Scholar
  111. 111.
    Heinonen, O.P., and D. Albanes, The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers (The Alpha-tocopherol, Beta Carotene Cancer Prevention Study Group), Ibid.: 1029–1034 (1994).CrossRefGoogle Scholar
  112. 112.
    Henekens, C.H., J.E. Buring, J.E. Manson, M. Stamper, B. Rosner, N.R. Cook, C. Belanger, F. Lamotte, J.M. Gaziano, P.M. Ridker, W. Willet, and R. Peto, Lack of Effect of Long-Term Supplementation With β-Carotene on the Incidence of Malignant Neoplasma and Cardiovascular Disease, Ibid.:1145–1149 (1996).CrossRefGoogle Scholar
  113. 113.
    Gillman, M.W., L.A. Cupples, D. Gagnou, B.M. Posner, R.C. Ellison, W.P. Castelli, and P.A. Wolf, Protective Effect of Fruits and Vegetables on Development of Stroke in Men, J. Am. Med. Assoc. 273:1113–1117 (1995).CrossRefGoogle Scholar
  114. 114.
    Stephens, N.G., A. Parsons, P.M. Schofield, F. Kelly, K. Cheeseman, M.J. Mitchinson, and M.J. Brown, Randomised Controlled Trial of Vitamin E in Patients with Coronary Diseases: Cambridge Heart Antioxidant Study (CHAOS), Lancet 347:781–786 (1996).PubMedCrossRefGoogle Scholar
  115. 115.
    Grey, K.F., Ten Year Retrospective on the Antioxidant Hypothesis of Atherosclerosis: Threshold Plasma Levels of Antioxidant Micronutrients Related to Minimum Cardiovascular Risk, J. Nutr. Biochem. 6:206–236 (1996).Google Scholar
  116. 116.
    Omenn, G.S., G.E. Goodman, M.D. Thornquist, J. Balmes, M.R. Cullen, A. Glass, J.P. Keogh, F.L. Meyskens, B. Valanis, J.H. Williams, S. Barnhart and S. Hammer, Effect of a Combination of β-Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease, New Engl. J. Med. 334:1150–1155 (1996).PubMedCrossRefGoogle Scholar
  117. 117.
    Spencer, J.P.E., A. Jenner, O.I. Aruoma, C.E. Cross, R. Wu, and B. Halliwell, Oxidative DNA Damage in Human Respiratory Tract Epithelial Cells. Time Course in Relation to DNA Strand Breakage, Biochem. Biophys. Res. Commun. 224:17–22 (1996).PubMedCrossRefGoogle Scholar
  118. 118.
    Jaruga, P., and M. Dizdaroglu, Repair of Products of Oxidative DNA Base Damage in Human Cells, Nucleic Acids Res. 24:1389–1394 (1996).PubMedCrossRefGoogle Scholar
  119. 119.
    Nackerdien, Z., R. Olinski, and M. Dizdaroglu, DNA Base Damage in Chromatin of γ-Irradiated Cultured Human Cells, Free Radical Res. Commun. 16:259–273 (1992).Google Scholar
  120. 120.
    Breen, A.P., and J.A. Murphy, Reactions of Oxyl Radicals with DNA, Free Radical Biol. Med. 18:1033–1077 (1995).CrossRefGoogle Scholar
  121. 121.
    Brynes, R.W., Evidence for Involvement of Multiple Iron Species in DNA Single-Strand Scission by H2O2 in HL-60 Cells, Ibid.:399–406 (1996).CrossRefGoogle Scholar
  122. 122.
    Klein, C.B., K. Frenkel, and M. Costa, The Role of Oxidative Processes in Metal Carcinogenesis, Chem. Res. Toxicol. 4:592–604 (1991).PubMedCrossRefGoogle Scholar
  123. 123.
    Pezzano, H., and F. Podo, Structure of Binary Complexes of Mono and Polynucleotides with Metal Ions of the First Transition Group, Chem. Rev. 80:365–401 (1980).CrossRefGoogle Scholar
  124. 124.
    Bryan, S.E., D.L. Vizard, D.A. Beary, R.A. LaBiche, and K.J. Hardy, Partitioning of Zinc and Copper Within Subnuclear Nucleoprotein Particles, Nucl. Acids Res. 9:5811–5823 (1981).PubMedCrossRefGoogle Scholar
  125. 125.
    Halliwell, B., and O.I. Aruoma, DNA and Free Radicals, Ellis Horwood, London, 1993.Google Scholar
  126. 126.
    Aruoma, O.I., B. Halliwell, and M. Dizdaroglu, Iron Ion Dependent Modification of Bases in DNA by the Superoxide Radical Generating System Hypoxanthine/Xanthine Oxidase, J. Biol. Chem. 264:20509–20512 (1989).PubMedGoogle Scholar
  127. 127.
    Dizdaroglu, M., Chemical Determination of Free Radical Induced Damage to DNA, Free Radical Biol. Med. 10:225–242 (1991).CrossRefGoogle Scholar
  128. 128.
    Spencer, J.P.E., A. Jenner, O.I. Aruoma, P.J. Evans, H. Kaur, D.T. Dexter, P. Jenner, A.J. Lees, DC. Marsden, and B. Halliwell, Intense Oxidative DNA Damage Promoted by l-DOPA and Its Metabolites. Implications for Neurodegenerative Disease, FEBS Lett. 353:246–250 (1994).PubMedCrossRefGoogle Scholar
  129. 129.
    Collins, A.R., S.J. Duthie, and V.L. Dobson, Direct Enzymic Detection of Endogenous Oxidative Base Damage in Human Lymphocyte DNA, Carcinogenesis 14:1733–1735 (1993).PubMedCrossRefGoogle Scholar
  130. 130.
    Herbert, K.E., M.D. Evans, M.T.V. Finnegan, S. Farooq, N. Mistry, I.D. Podmore, P. Farmer, and J. Lunec, A Novel HPLC Procedure for the Analysis of 8-Oxoguanine in DNA, Free Radical Biol. Med. 20:467–473 (1996).CrossRefGoogle Scholar
  131. 131.
    Shigenaga, M.K., C.J. Gimeno, and B.N. Ames, Urinary 8-Hydroxy 2′Deoxyguanosine as a Biological Marker of in vivo Oxidative DNA Damage, Proc. Natl. Acad. Sci. USA 86:9697–9701 (1989).PubMedCrossRefADSGoogle Scholar
  132. 132.
    Loft, S., A. Fischer-Nielsen, and I.B. Jeding, 8-Hydroxydeoxyguanosine as a Urinary Marker of Oxidative DNA Damage, J. Toxicol. Environ. Health 40:391–404 (1993).PubMedCrossRefGoogle Scholar
  133. 133.
    Stillwell, W.G., H.X. Xu, J.A. Adkins, J.S. Wishnok, and S.R. Tannenbaum, Analysis of Methylated and Oxidized Purines in Urine by Capillary Gas Chromatography-Mass Spectrometry, Chem. Res. Tox. 2:94–99 (1989).CrossRefGoogle Scholar
  134. 134.
    Teixeira, A.J.R., J.H. Gommers-Ampt, G. van de Werken, J.G. Westra, J.F.C. Stavenviter, and A.P.J.M. de Jong, Method for the Analysis of Oxidized Nucleosides by Gas Chromatography/Mass Spectrometry, Anal. Biochem. 214:474–483 (1993).PubMedCrossRefGoogle Scholar
  135. 135.
    Sakumi, K., M. Furuichi, T. Tsuzuki, T. Kakuma, S. Kawabata, H. Maki, and M. Sekiguchi, Cloning and Expression of cDNA for a Human Enzyme That Hydrolyzes 8-Oxo-dGTP, a Mutagenic Substrate for DNA Synthesis, J. Biol. Chem. 268:23524–23530 (1993).PubMedGoogle Scholar
  136. 136.
    Mo, J.Y., H. Maki, and M. Sekiguchi, Hydrolytic Elimination of a Mutagenic Nucleotide, 8-OxodGTP, by Human 18-Kilodalton Protein; Sanitization of Nucleotide Pool, Proc. Natl. Acad. Sci. USA 89:11021–11025 (1992).PubMedCrossRefADSGoogle Scholar
  137. 137.
    Halliwell, B., and O.I. Aruoma, Free Radicals and Antioxidants: The Need for in vivo Markers of Oxidative Stress, in Antioxidant Methodology: In Vivo and In Vitro Concepts, edited by O.I. Aruoma and S. Cuppett, AOCS Press, Champaign, 1997.Google Scholar
  138. 138.
    Goetzl, E.J., J.M. Woods, and R.R. Gorman, Stimulation of Human Eosinophil and Neutrophil Polymorphonuclear Leukocyte Chemotaxis and Random Migration by 12-l-Hydroxy-5,8,10,14-eicosatetraenoic Acid, J. Clin. Invest. 59:179–183 (1977).PubMedGoogle Scholar
  139. 139.
    O’Flaherty, J.T., and J. Nishihira, 5-Hydroxyeicosatetraenoate Promotes Ca2+ and Protein Kinase Mobilisation in Neutrophils, Biochem. Biophys. Res. Commun. 148:575–581 (1987).PubMedCrossRefGoogle Scholar
  140. 140.
    Won, J.G., and D.N. Orth, The Role of Lipoxygenase Metabolite of Arachidonic Acid in the Regulation of Adrenocorticotropin Secretion by Perfused Rat Anterior Pituitary Cells, Endocrinology 135:1496–1503 (1994).PubMedCrossRefGoogle Scholar
  141. 141.
    Joulain, C., N. Meskini, G. Anker, M. Lagarde, and A.F. Prigent, Esterification of 12(S)-Hydroxy-5,8,10,14-eicosatetraenoic Acid into the Phospholipids of Human Peripheral Blood Mononuclear Cells: Inhibition of the Proliferative Response, J. Cell. Physiol. 164:154–163 (1995).PubMedCrossRefGoogle Scholar
  142. 142.
    Bourdeau, A., M. Mourahir, J.C. Souberbielle, P. Bonnet, P. Herviaux, C. Sachs, and M. Lieberherr, Effects of Lipoxygenase Products of Arachidonate Metabolism on Parathyroid Hormone Secretion, Endocrinology 135:1109–1112 (1994).PubMedCrossRefGoogle Scholar
  143. 143.
    Takata, S., A. Papayianni, M. Matsubara, W. Jimenez, P.H. Pronovost, and H.R. Brady, 15-Hydroxyeicosatetraenoic Acid Inhibits Neutrophil Migration Across Cytokine-Activated Endothelium, Am. J. Pathol. 145:541–549 (1994).PubMedGoogle Scholar
  144. 144.
    Noourooz-Zadeh, J., N.K. Gopaul, S. Barrow, A.I. Mallet, and E.E. Anggärd, Analysis of F2-Isoprostanes as Indicators of Non-enzymatic Lipid Peroxidation in vivo by Gas Chromatography-Mass Spectrometry: Development of a Solid-Phase Extraction Procedure, J. Chromatogr. B667:199–208 (1995).Google Scholar
  145. 145.
    Guido, G.M., R. McKenna, and W.R. Matthews, Quantitation of Hydroperoxy-Eicosatetraenoic Acids and Hydroxy-Eicosatetraenoic Acids as Indicators of Lipid Peroxidation Using Gas Chromatography-Mass Spectrometry, Anal. Biochem. 209:123–129 (1993).PubMedCrossRefGoogle Scholar
  146. 146.
    Morrow, J.D., J.A. Awad, T. Kato, K. Takahashi, K.F. Badr, L.J. Roberts, and R.F. Burk, Formation of Novel Non-cyclooxygenase Derived Prostanoids (F2-isoprostanes) in Carbontetrachloride Hepatotoxicity: An Animal Model of Lipid Peroxidation, J. Clin. Invest. 90:2502–2507 (1992).PubMedGoogle Scholar
  147. 147.
    Bachi, A., E. Zuccato, M. Beraldi, R. Faneli, and C. Chiabrando, Measurement of Urinary 8-Epi-prostaglandin F, A Novel Index of Lipid Peroxidation in vivo, by Immunoaffinity Extraction/Gas Chromatography-Mass Spectrometry. Basal Levels in Smokers and Nonsmokers, Free Radical Biol. Med. 20:619–624 (1996).CrossRefGoogle Scholar
  148. 148.
    Morrow, J.D., T.A. Minton, C.R. Mukundan, M.D. Campbell, W.E. Zackert, V.C. Daniel, K.F. Badr, I.A. Badr, and L.J. Roberts, Free Radical-Induced Generation of Isoprostanes in vivo. Evidence for the Formation of D-Ring and E-Ring Isoprostanes, J. Biol. Chem. 269:4317–4326 (1994).PubMedGoogle Scholar
  149. 149.
    Halliwell, B., Oxidative Stress, Nutrition and Health. Experimental Stratgegies for Optimization of Nutritional Antioxidant Intake in Humans, Free Radical Res. 25:57–74 (1996).Google Scholar
  150. 150.
    Halliwell, B., Biochemical Mechanisms Accounting for the Toxic Action of Oxygen on Living Organisms. The Key Role of Superoxide Dismutase, Cell Biol. Int. Rep. 2:113–118 (1978).PubMedCrossRefGoogle Scholar
  151. 151.
    Ramotar, D., and B. Demple, Enzymes That Repair Oxidative Damage to DNA, in DNA and Free Radicals, edited by B. Halliwell and O.I. Aruoma, Ellis Horwood, London, 1993, pp. 166–191.Google Scholar
  152. 152.
    Dean, R.T., J.V. Hunt, A.J. Grant, Y. Yamamoto, and E. Niki, Free Radical Damage to Proteins: The Influence of the Relative Localization of Radical Generation, Antioxidants and Target Proteins, Free Radical Biol. Med. 11:161–168 (1991).CrossRefGoogle Scholar
  153. 153.
    Wells-Knecht, M.C., T.G. Huggins, D.G. Dyer, S.R. Thorpe, and J.W. Baynes, Oxidized Amino Acids in Lens Proteins with Age. Measurement of o-Tyrosine and Dityrosine in the Aging Human Lens, J. Biol. Chem. 268:12348–12352 (1993).PubMedGoogle Scholar
  154. 154.
    Reznick, A.Z., and L. Packer, Oxidative Damage to Proteins: Spectrophotometric Method for Carbonyl Assay, Methods Enzymol, 233:357–363 (1994).PubMedGoogle Scholar
  155. 155.
    Amici, A., R.L. Levine, L. Tsai, and E.R. Stadtman, Conversion of Amino Acid Residues in Proteins and Amino Acid Homopolymers to Carbonyl Derivatives by Metal-Catalyzed Oxidation Reactions, J. Biol. Chem. 264:3341–3346 (1989).PubMedGoogle Scholar
  156. 156.
    Cao, G., and R.G. Cutler, Protein Oxidation and Aging, Difficulties in Measuring Reactive Protein Carbonyls in Tissues Using 2,4-Dinitrophenylhydrazine, Arch. Biochem. Biophys. 320:106–114 (1995).PubMedCrossRefGoogle Scholar
  157. 157.
    Lyras, L., P.J. Shaw, P.J. Evans, and B. Halliwell, Oxidative Damage and Motor Neurone Disease. Difficulties in the Measurement of Protein Carbonyls in Human Brain Tissue, Free Radical Res. 24:397–406 (1996).Google Scholar
  158. 158.
    Levine, R.L., J.A. Williams, E.R. Stadtman, and E. Shacter, Carbonyl Assays for Determination of Oxidatively Modified Proteins, Methods Enzymol. 233:346–357 (1994).PubMedCrossRefGoogle Scholar
  159. 159.
    Keller, J., N.C. Halmes, J.A. Hinson, and N.R. Pumford, Immunochemical Detection of Oxidized Proteins, Chem. Res. Toxicol. 6:430–433 (1993).PubMedCrossRefGoogle Scholar
  160. 160.
    Oliver, C.N., B.A. Ahn, E.J. Moerman, S. Goldstein, and E.R. Stadman, Age-Related Changes in Oxidized Proteins, J. Biol. Chem. 262:5488–5491 (1987).PubMedGoogle Scholar
  161. 161.
    Ambe, K.S., and A.L. Tappel, Oxidative Damage to Amino Acids, Peptides and Proteins by Radiation, J. Food Sci. 26:448–451 (1962).CrossRefGoogle Scholar
  162. 162.
    Dean, R.T., S. Fu, R. Stocker, and M.J. Davies, Biochemistry and Pathology of Radical Mediated Protein Oxidation, Biochem. J. 324:1–18 (1997).PubMedGoogle Scholar
  163. 163.
    S. Fu, S., R.T. Dean, and M.J. Davies, Molecular Aspects of Free Radical Damage to Proteins, in Molecular Biology of Free Radicals in Human Diseases, edited by O.I. Aruoma and B. Halliwell, OICA International, Saint Lucia, 1998, pp. 29–56.Google Scholar
  164. 164.
    Aruoma, O.I., Extracts as Antioxidant Prophylactic Agents, INFORM 8:1236–1242 (1997).Google Scholar

Copyright information

© AOCS Press 1998

Authors and Affiliations

  • Okezie I. Aruoma
    • 1
  1. 1.OICA International, Saint Lucia, West Indies, and Pharmacology GroupKing’s College LondonLondonGreat Britain

Personalised recommendations