Does vitamin C act as a pro-oxidant under physiological conditions?

FASEB Journal

Volumn 13, Issue 9, 1999, Pages 1007-1024

  Carr, Anitra ^a   Frei, Balz ^a  

^a OREGON STATE UNIVERSITY   (United States)

Author keywords

Antioxidant; DNA; Iron; Lipid; Protein

Indexed keywords

ASCORBIC ACID; DNA; IRON; LIPID; NITROGEN; OXIDIZING AGENT; PROTEIN; REACTIVE OXYGEN METABOLITE; SCAVENGER;

ANIMAL EXPERIMENT; ASCORBIC ACID DEFICIENCY; CONTROLLED STUDY; DNA DAMAGE; ENZYME ACTIVE SITE; GUINEA PIG; HUMAN; HUMAN CELL; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SCURVY; VITAMIN INTAKE;

ANIMALIA; CAVIA PORCELLUS; SUS SCROFA;

EID: 0033040739     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fasebj.13.9.1007     Document Type: Review

References (148)

1. Frei, B., England, L., and Ames, B. N. (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. U. S. A. 86, 6377-6381
2. Frei, B., Stocker, R., England, L., and Ames, B. N. (1990) Ascorbate: the most effective antioxidant in human blood plasma. Adv. Exp. Med. Biol. 264, 155-163
3. Halliwell, B. (1996) Vitamin C: antioxidant or pro-oxidant in vivo? Free Rad. Res. 25, 439-454
4. Buettner, G. R., and Jurkiewicz, B. A. (1996) Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat. Res. 145, 532-541
5. Chesney, J. A., Mahoney, J. R., and Eaton, J. W. (1991) A spectrophotometric assay for chlorine-containing compounds. Anal. Biochem. 196, 262-266
6. Menzel, D. B. (1971) Oxidation of biologically active reducing substances by ozone. Arch. Environ. Health 23, 149-153
7. Chou, P. T., and Khan, A. U. (1983) L-Ascorbic acid quenching of singlet delta molecular oxygen in aqueous media: generalized antioxidant property of vitamin C. Biochem. Biophys. Res. Commun. 115, 932-937
8. Cooney, R. V., Ross, P. D., and Bartolini, G. L. (1986) N-Nitrosation and N-nitration of morpholine by nitrogen dioxide: inhibition by ascorbate, glutathione and α-tocopherol. Cancer Lett. 32, 83-90
9. Licht, W. R., Tannenbaum, S. R., and Deen, W. M. (1988) Use of ascorbic acid to inhibit nitrosation: kinetic and mass transfer considerations for an in vitro system. Carcinogenesis 9, 365-372
10. Kveder, M., Pifat, G., Pecar, S., Schara, M., Ramos, P., and Esterbauer, H. (1997) Nitroxide reduction with ascorbic acid in spin labeled human plasma LDL and VLDL. Chem. Phys. Lipids 85, 1-12
11. Bartlett, D., Church, D. F., Bounds, P. L., and Koppenol, W. H. (1995) The kinetics of the oxidation of L-ascorbic acid by peroxynitrite. Free Rad. Biol. Med. 18, 85-92
12. Edge, R., and Truscott, T. G. (1997) Prooxidant and antioxidant reaction mechanisms of carotene and radical interactions with vitamins E and C. Nutrition 13, 992-994
13. Cross, C. E., van der Vliet, A., O'Neill, C. A., Louie, S., and Halliwell, B. (1994) Oxidants, antioxidants and respiratory tract lining fluids. Environ. Health Perspect. 102, 185-191
14. Lykkesfeldt, J., Loft, S., Nielsen, J. B., and Poulsen, H. E. (1997) Ascorbic acid and dehydroascorbic acid as biomarkers of oxidative stress caused by smoking. Am. J. Clin. Nutr. 65, 959-963
15. Neuzil, J., Thomas, S. R., and Stocker, R. (1997) Requirement for, promotion, or inhibition by α-tocopherol of radical-induced initiation of plasma lipoprotein lipid peroxidation. Free Rad. Biol. Med. 22, 57-71
16. Bowry, V. W., Mohr, D., Cleary, J., and Stocker, R. (1995) Prevention of tocopherol-mediated peroxidation in ubiquinol10-free human low density lipoprotein. J. Biol. Chem. 270, 5756-5763
17. May, J. M., Qu, Z. C., and Mendiratta, S. (1998) Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid. Arch. Biochem. Biophys. 349, 281-289
18. Jacob, R. A., Kutnink, M. A., Csallany, A. S., Daroszewska, M., and Burton, G. W. (1996) Vitamin C nutriture has little short-term effect on vitamin E concentrations in healthy women. J. Nutr. 126, 2268-2277
19. Burton, G. W., Wronska, U., Stone, L., Foster, D. O., and Ingold, K. U. (1990) Biokinetics of dietary RRR-α-tocopherol in the male guinea pig at three dietary levels of vitamin C and two levels of vitamin E. Evidence that vitamin C does not 'spare' vitamin E in vivo. Lipids 25, 199-210
20. Meister, A. (1994) Glutathione-ascorbic acid antioxidant system in animals. J. Biol. Chem. 269, 9397-9400
21. Buettner, G. R. (1993) The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol, and ascorbate. Arch. Biochem. Biophys. 300, 535-543
22. Wells, W. W., and Jung, C. (1997) Regeneration of vitamin C. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 109-121, Marcel Dekker, Inc., New York
23. May, J. M., Cobb, C. E., Mendiratta, S., Hill, K. E., and Burk, R. F. (1998) Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. J. Biol. Chem. 273, 23039-23045
24. May, J. M., Mendiratta, S., Hill, K. E., and Burk, R. F. (1997) Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. J. Biol. Chem. 272, 22607-22610
25. Park, J. B., and Levine, M. (1996) Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: identification as glutaredoxin. Biochem. J. 315, 931-938
26. Levine, M. (1986) New concepts in the biology and biochemistry of ascorbic acid. New Engl. J. Med. 314, 892-902
27. Bendich, A., and Cohen, M. (1990) Ascorbic acid safety: analysis of factors affecting iron absorption. Toxicol. Lett. 51, 189-201
28. Halliwell, B., and Gutteridge, J. M. C. (1986) Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch. Biochem. Biophys. 246, 501-514
29. Halliwell, B., and Gutteridge, J. M. C. (1989) Free Radicals in Biology and Medicine. Clarendon Press, Oxford
30. Woodall, A. A., and Ames, B. N. (1997) Diet and oxidative damage to DNA: the importance of ascorbate as an antioxidant. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 193-203, Marcel Dekker, Inc., New York
31. Poulsen, H. E., Prieme, H., and Loft, S. (1998) Role of oxidative DNA damage in cancer initiation and promotion. Eur. J. Cancer Prev. 7, 9-16
32. Enstrom, J. E. (1997) Vitamin C in prospective epidemiological studies. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 381-398, Marcel Dekker, Inc., New York
33. Block, G. (1991) Vitamin C and cancer prevention: the epidemiologic evidence. Am. J. Clin. Nutr. 53, 270S-282S
34. Jenner, A., England, T. G., Aruoma, O. I., and Halliwell, B. (1998) Measurement of oxidative DNA damage by gas chromatographymass spectrometry: ethanethiol prevents artifactual generation of oxidized DNA bases. Biochem. J. 331, 365-369
35. Collins, A., Cadet, J., Epe, B., and Gedik, C. (1997) Problems in the measurement of 8-oxoguanine in human DNA. Carcinogenesis 18, 1833-1836
36. Helbock, H. J., Beckman, K. B., Shigenaga, M. K., Walter, P. B., Woodall, A. A., Yeo, H. C., and Ames, B. N. (1998) DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. Proc. Natl. Acad. Sci. U. S. A. 95, 288-293
37. Pflaum, M., Will, O., and Epe, B. (1997) Determination of steady-state levels of oxidative DNA base modifications in mammalian cells by means of repair endonucleases. Carcinogenesis 18, 2225-2231
38. Drouin, R., Rodriguez, H., Gao, S. W., Gebreyes, Z., O'Connor, T. R., Holmquist, G. P., and Akman, S. A. (1996) Cupric ion/ascorbate/hydrogen peroxide-induced DNA damage: DNA-bound copper ion primarily induces base modifications. Free Rad. Biol. Med. 21, 261-273
39. Fischer-Nielsen, A., Poulsen, H. E., and Loft, S. (1992) 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid. Free Rad. Biol. Med. 13, 121-126
40. Hu, M. L., and Shih, M. K. (1997) Ascorbic acid inhibits lipid peroxidation but enhances DNA damage in rat liver nuclei incubated with iron ions. Free Rad. Res. 26, 585-592
41. Fiala, E. S., Sodum, R. S., Bhattacharya, M., and Li, H. (1996) (-)-Epigallocatechin gallate, a polyphenolic tea antioxidant, inhibits peroxynitrite-mediated formation of 8-oxodeoxy-guanosine and 3-nitrotyrosine. Experientia 52, 922-926
42. Wei, H., Cai, Q., Tian, L., and Lebwohl, M. (1998) Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid, and protein in vitro and in vivo. Carcinogenesis 19, 1013-1018
43. Noroozi, M., Angerson, W. J., and Lean, M. E. J. (1998) Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Am. J. Clin. Nutr. 67, 1210-1218
44. Fischer-Nielsen, A., Loft, S., and Jensen, K. G. (1993) Effect of ascorbate and 5-aminosalicylic acid on light-induced 8-hydroxydeoxyguanosine formation in V79 Chinese hamster cells. Carcinogenesis 14, 2431-2433
45. Pflaum, M., Kielbassa, C., Garmyn, M., and Epe, B. (1998) Oxidative DNA damage induced by visible light in mammalian cells: extent, inhibition by antioxidants and genotoxic effects. Mutat. Res. 408, 137-146
46. Singh, N. P. (1997) Sodium ascorbate induces DNA single-strand breaks in human cells in vitro. Mutat. Res. 375, 195-203
47. Anderson, D., Yu, T. W., Phillips, B. J., and Schmezer, P. (1994) The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay. Mutat. Res. 307, 261-271
48. Green, M. H. L., Lowe, J. E., Waugh, A. P. W., Aldridge, K. E., Cole, J., and Arlett, C. F. (1994) Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells. Mutat. Res. 316, 91-102
49. Cadenas, S., Barja, G., Poulsen, H. E., and Loft, S. (1997) Oxidative DNA damage estimated by oxo8dG in the liver of guinea-pigs supplemented with graded dietary doses of ascorbic acid and α-tocopherol. Carcinogenesis 18, 2373-2377
50. Reddy, V. N., Giblin, F. J., Lin, J. R., and Chakrapani, B. (1998) The effect of aqueous humor ascorbate on ultraviolet-B-induced DNA damage in lens epithelium. Invest. Opthalmol. Vis. Sci. 39, 344-350
51. Podmore, I. D., Griffiths, H. R., Herbert, K. E., Mistry, N., Mistry, P., and Lunec, J. (1998) Vitamin C exhibits pro-oxidant properties. Nature (London) 392, 559
52. Cooke, M. S., Evans, M. D., Podmore, I. D., Herbert, K. E., Mistry, N., Mistry, P., Hickenbotham, P. T., Hussieni, A., Griffiths, H. R., and Lunec, J. (1998) Novel repair action of vitamin C upon in vivo oxidative DNA damage. FEBS Lett. 363, 363-367
53. Rehman, A., Collis, C. S., Yang, M., Kelly, M., Diplock, A. T., Halliwell, B., and Rice-Evans, C. (1998) The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem. Biophys. Res. Commun. 246, 293-298
54. Fraga, C. G., Motchnik, P. A., Shigenaga, M. K., Helbock, H. J., Jacob, R. A., and Ames, B. N. (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl. Acad Sci. U. S. A. 88, 11003-11006
55. Lee, B. M., Lee, S. K., and Kim, H. S. (1998) Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, β-carotene and red ginseng). Cancer Lett. 132, 219-227
56. Prieme, H., Loft, S., Nyyssonen, K., Salonen, J. T., and Poulsen, H. E. (1997) No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion in smokers. Am. J. Clin. Nutr. 65, 503-507
57. Anderson, D., Phillips, B. J., Yu, T., Edwards, A. J., Ayesh, R., and Butterworth, K. R. (1997) The effects of vitamin C supplementation on biomarkers of oxygen radical generated damage in human volunteers with 'low' or 'high' cholesterol levels. Environ. Mol. Mutagen. 30, 161-174
58. Panayiotidis, M., and Collins, A. R. (1997) Ex vivo assessment of lymphocyte antioxidant status using the comet assay. Free Rad. Res. 27, 533-537
59. Poulsen, H. E., Weimann, A., Salonen, J. T., Nyyssonen, K., Loft, S., Cadet, J., Douki, T., and Ravanat, J. (1998) Does vitamin C have a pro-oxidant effect? Nature (London) 395, 231-232
60. Levine, M. A., Daruwala, R. C., Park, J. B., Rumsey, S. C., and Wang, Y. (1998) Does vitamin C have a pro-oxidant effect? Nature (London) 395, 231
61. Wood, M. L., Esteve, A., Morningstar, M. L., Kuziemko, G. M., and Essigmann, J. M. (1992) Genetic effects of oxidative DNA damage: comparative mutagenesis of 7,8-dihydro-8-oxoguanine and 7,8-dihydro-8-oxoadenine in Escherichia coli. Nucleic Acids Res. 20, 6023-6032
62. Podmore, I. D., Griffiths, H. R., Herbert, K. E., Mistry, N., Mistry, P., and Lunec, J. (1998) Does vitamin C have a pro-oxidant effect? Nature (London) 395, 232
63. Fraga, C. G., Motchnik, P. A., Wyrobek, A. J., Rempel, D. M., and Ames, B. N. (1996) Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat. Res. 351, 199-203
64. Lindahl, T. (1993) Instability and decay of the primary structure of DNA. Nature (London) 362, 709-715
65. Steinbrecher, U. P., Zhang, H., and Lougheed, M. (1990) Role of oxidatively modified LDL in atherosclerosis. Free Rad. Biol. Med. 9, 155-168
66. Frei, B. (1997) Vitamin C as an antiatherogen: mechanisms of action. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 163-182, Marcel Dekker, Inc., New York
67. de Zwart, L. L., Meerman, J. H. N., Commandeur, J. N. M., and Vermeulen, N. P. E. (1999) Biomarkers of free radical damage: applications in experimental animals and in humans. Free Rad. Biol. Med. 26, 202-226
68. 2-isoprostanes, are present in increased amounts in human atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 17, 3236-3241
69. 2-isoprostanes in human atherosclerotic lesions. J. Clin. Invest. 100, 2028-2034
70. Suarna, C., Dean, R. T., Southwell-Keeley, P. T., Moore, D. E., and Stocker, R. (1997) Separation and characterization of cholesterol oxo-and hydroxy-linoleate isolated from human atherosclerotic plaque. Free Rad. Res. 27, 397-408
71. Lynch, S. M., Gaziano, J. M., and Frei, B. (1996) Ascorbic acid and atherosclerotic cardiovascular disease. In Ascorbic Acid: Biochemistry and Biomedical Cell Biology (Harris, J.R., ed) pp. 331-367, Plenum Press, New York
72. Jha, P., Flather, M., Lonn, E., Farkouh, M., and Yusuf, S. (1995) The antioxidant vitamins and cardiovascular disease: a critical review of epidemiologic and clinical trial data. Ann. Int. Med. 123, 860-872
73. Frei, B., Yamamoto, Y., Niclas, D., and Ames, B. N. (1988) Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma. Anal. Biochem. 175, 120-130
74. Frei, B., and Gaziano, J. M. (1993) Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as predictors of the susceptibility of human LDL to metal ion-dependent and -independent oxidation. J Lipid Res. 34, 2135-2145
75. Frei, B., Stocker, R., and Ames, B. N. (1988) Antioxidant defenses and lipid peroxidation in human blood plasma. Proc. Natl. Acad. Sci. U. S. A. 85, 9748-9752
76. 2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J. Clin. Invest. 93, 998-1004
77. Thomas, S. R., Davies, M. J., and Stocker, R. (1998) Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. Chem. Res. Toxicol. 11, 484-494
78. Cross, C. E., O'Neill, C. A., Reznick, A. Z., Hu, M. L., Marcocci, L., Packer, L., and Frei, B. (1993) Cigarette smoke oxidation of human plasma constituents. Ann. NY Acad. Sci. 686, 72-89
79. Frei, B., Forte, T. M., Ames, B. N., and Cross, C. E. (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma: protective effects of ascorbic acid. Biochem. J. 277, 133-138
80. Berger, T. M., Polidori, M. C., Dabbagh, A., Evans, P. J., Halliwell, B., Morrow, J. D., Roberts, L. J., and Frei, B. (1997) Antioxidant activity of vitamin C in iron-overloaded human plasma. J. Biol. Chem. 272, 15656-15660
81. Dasgupta, A., and Zdunek, T. (1992) In vitro lipid peroxidation of human serum catalyzed by cupric ion: antioxidant rather than prooxidant role of ascorbate. Life Sci. 50, 875-882
82. Kunert, K. J., and Tappel, A. L. (1983) The effect of vitamin C on in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production. Lipids 18, 271-274
83. Dillard, C. J., Kunert, K. J., and Tappel, A. L. (1982) Effects of vitamin E, ascorbic acid and mannitol on alloxan-induced lipid peroxidation in rats. Arch. Biochem. Biophys. 216, 204-212
84. Kang, S. A., Jang, Y. J., and Park, H. (1998) In vivo dual effect of vitamin C on paraquat-induced lung damage: dependence on released metals from the damaged tissue. Free Rad. Res. 28, 93-107
85. Barja, G., Lopez-Torres, M., Perez-Campo, R., Rojas, C., Cadenas, S., Prat, J., and Pamplona, R. (1994) Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. Free Rad. Biol. Med. 17, 105-115
86. Cadenas, S., Rojas, C., and Barja, G. (1998) Endotoxin increases oxidative injury to proteins in guinea pig liver, protection by dietary vitamin C. Pharmacol. Toxicol. 82, 11-18
87. Cadenas, S., Lertsiri, S., Otsuka, M., Barga, G., and Miyazawa, T. (1996) Phospholipid hydroperoxides and lipid peroxidation in liver and plasma of ODS rats supplemented with α-tocopherol and ascorbic acid. Free Rad. Res. 24, 485-493
88. Kimura, H., Yamada, Y., Morita, Y., Ikeda, H., and Matsuo, T. (1992) Dietary ascorbic acid depresses plasma and low density lipoprotein lipid peroxidation in genetically scorbutic rats. J. Nutr. 122, 1904-1909
89. Tanaka, K., Hashimoto, T., Tokumaru, S., Iguchi, H., and Kojo, S. (1997) Interactions between vitamin C and vitamin E are observed in tissues of inherently scorbutic rats. J. Nutr. 127, 2060-2064
90. Helen, A., and Vijayammal, P. L. (1997) Vitamin C supplementation on hepatic oxidative stress induced by cigarette smoke. J. Appl. Toxicol. 17, 289-295
91. Collis, C. S., Yang, M., Diplock, A. T., Hallinan, T., and Rice-Evans, C. A. (1997) Effects of co-supplementation of iron with ascorbic acid on antioxidant-pro-oxidant balance in the guinea pig. Free Rad. Res. 27, 113-121
92. Reilly, M., Delanty, N., Lawson, J. A., and Fitzgerald, G. A. (1996) Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 94, 19-25
93. Gokce, N., Frei, B., Holbrook, M., Olesiak, M., and Vita, J. A. (1998) Chronic ascorbic acid treatment improves endothelial function in patients with coronary artery disease. Circulation 98, 1-175 (abstr.)
94. Samman, S., Brown, A. J., Beltran, C., and Singh, S. (1997) The effect of ascorbic acid on plasma lipids and oxidisability of LDL in male smokers. Eur. J. Clin. Nutr. 51, 472-477
95. Nyyssonen, K., Poulsen, H. E., Hayn, M., Agerbo, P., Porkkala-Sarataho, E., Kaikkonen, J., Salonen, R., and Salonen, J. T. (1997) Effect of supplementation of smoking men with plain or slow-release ascorbic acid on lipoprotein oxidation. Eur. J. Clin. Nutr. 51, 154-163
96. Fuller, C. J., Grundy, S. M., Norkus, E. P., and Jialal, I. (1996) Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 119, 139-150
97. Mulholland, C. W., Strain, J. J., and Trinick, T. R. (1996) Serum antioxidant potential, and lipoprotein oxidation in female smokers following vitamin C supplementation. Int. J. Food Sci. Nutr. 47, 227-231
98. Harats, D., Ben-Naim, M., Dabach, Y., Hollander, G., Havivi, E., Stein, O., and Stein, Y. (1990) Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 85, 47-54
99. Naidoo, D., and Lux, O. (1998) The effect of vitamin C and E supplementation on lipid and urate oxidation products in plasma. Nutr. Res. 18, 953-961
100. Cadenas, S., Rojas, C., Mendez, J., Herrero, A., and Barja, G. (1996) Vitamin E decreases urine lipid peroxidation products in young healthy human volunteers under normal conditions. Pharmacol. Toxicol. 79, 247-253
101. Wen, Y., Cooke, T., and Feely, J. (1997) The effect of pharmacological supplementation with vitamin C on low-density lipoprotein oxidation. Br. J. Clin. Pharmacol. 44, 94-97
102. Harats, D., Chevion, S., Nahir, M., Norman, Y., Sagee, O., and Berry, E. M. (1998) Citrus fruit supplementation reduces lipoprotein oxidation in young men ingesting a diet high in saturated fat: presumptive evidence for an interaction between vitamins C and E in vivo. Am. J. Clin. Nutr. 67, 240-245
103. Rifici, V. A., and Khachadurian, A. K. (1993) Dietary supplementation with vitamins C and E inhibits in vitro oxidation of lipoproteins. J. Am. Coll. Nutr. 12, 631-637
104. Alessio, H. M., Goldfarb, A.H., and Cao, G. (1997) Exercise-induced oxidative stress before and after vitamin C supplementation. Int. J. Sport Nutr. 7, 1-9
105. Sanchez-Quesada, J. L., Jorba, O., Payes, A., Otal, C., Serra-Grima, R., Gonzalez-Sastre, F., and Ordonez-Llanos, J. (1998) Ascorbic acid inhibits the increase in low-density lipoprotein (LDL) susceptibility to oxidation and the proportion of electronegantive LDL induced by intense aerobic exercise. Coronary Artery Dis. 9, 249-255
106. 2-isoprostanes) in smokers. New Engl. J. Med. 332, 1198-1203
107. Stocker, R., Bowry, V. W., and Frei, B. (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proc. Natl. Acad. Sci. U. S. A. 88, 1646-1650
108. Wayner, D. D., Burton, G. W., and Ingold, K. U. (1986) The antioxidant efficiency of vitamin C is concentration-dependent. Biochim. Biophys. Acta 884, 119-123
109. Dean, R. T., Fu, S., Stocker, R., and Davies, M. J. (1997) Biochemistry and pathology of radical-mediated protein oxidation. Biochem. J. 324, 1-18
110. Taylor, A., Dorey, C. K., and Nowell, T. (1997) Oxidative stress and ascorbate in relation to risk for cataract and age-related maculopathy. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 231-264, Marcel Dekker, Inc., New York
111. Berlett, B. S., and Stadtman, E. R. (1997) Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem. 272, 20313-20316
112. Ortwerth, B. J., and Monnier, V. M. (1997) Protein glycation by the oxidation products of ascorbic acid. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 123-142, Marcel Dekker, Inc., New York
113. Leeuwenburgh, C., Hardy, M. M., Hazen, S. L., Wagner, P., Oh-ishi, S., Steinbrecher, U. P., and Heinecke, J. W. (1997) Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. J. Biol. Chem. 272, 1433-1436
114. Hazen, S. L., and Heinecke, J. W. (1997) 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J. Clin. Invest. 99, 2075-2081
115. Fu, S., Davies, M. J., Stocker, R., and Dean, R. T. (1998) Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque. Biochem. J. 333, 519-525
116. Smith, M. A., Richey Harris, P. L., Sayer, L. M., Beckman, J. S., and Perry, G. (1997) Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 17, 2653-2657
117. Lee, K. W., Mossine, V., and Ortwerth, B. J. (1998) The relative ability of glucose and ascorbate to glycate and crosslink lens proteins in vitro. Exp. Eye Res. 67, 95-104
118. Atalay, A., Ogus, A., Bateman, O., and Slingsby, C. (1998) Vitamin C induced oxidation of eye lens gamma crystallins. Biochimie (Paris) 80, 283-288
119. Miyata, T., Inagi, R., Asahi, K., Yamada, Y., Horie, K., Sakai, H., Uchida, K., and Kurokawa, K. (1998) Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids. FEBS Lett. 437, 24-28
120. Linetsky, M., Ranson, N., and Ortwerth, B. J. (1998) The aggregation in human lens proteins blocks the scavenging of UVA-generated singlet oxygen by ascorbic acid and glutathione. Arch. Biochem. Biophys. 351, 180-188
121. Varma, S. D., Ali, A. H., Devamanoharan, P. S., and Morris, S. M. (1997) Nitrite-induced photo-oxidation of thiol and its implications in smog toxicity to the eye: prevention by ascorbate. J. Ocular Pharmacol. Ther. 13, 179-187
122. Reznick, A. Z., Cross, C. E., Hu, M. L., Suzuki, Y. J., Khwaja, S., Safadi, A., Motchnik, P. A., Packer, L., and Halliwell, B. (1992) Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation. Biochem. J. 286, 607-611
123. Hu, M., Louie, S., Cross, C. E., Motchnik, P., and Halliwell, B. (1993) Antioxidant protection against hypochlorous acid in human plasma. J. Lab. Clin. Med. 121, 257-262
124. Yamaguchi, T., Hishizume, T., Tanaka, M., Nakayama, M., Sugimoto, A., Ikeda, S., Nakajimi, H., and Horio, F. (1997) Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid. Eur. J. Biochem. 245, 233-240
125. Blondin, J., Baraji, V., Schwartz, E., Sadowski, J. A., and Taylor, A. (1986) Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate. J. Free Rad. Biol. Med. 2, 275-281
126. Tsao, C. S., Xu, L., and Young, M. (1990) Effect of dietary ascorbic acid on heat-induced eye lens protein damage in guinea pigs. Ophthalmic Res. 22, 106-110
127. Mannick, E. E., Bravo, L. E., Zarama, G., Realpe, J. L., Zhang, X. J., Ruiz, B., Fontham, E. T., Mera, R., Miller, M. J., and Correa, P. (1996) Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res. 56, 3238-3243
128. Yan, L., Traber, M. G., Kobuchi, H., Matsugo, S., Tritschler, H. J., and Packer, L. (1996) Efficacy of hypochlorous acid scavengers in the prevention of protein carbonyl formation. Arch. Biochem. Biophys. 327, 330-334
129. Hazell, L. J., and Stocker, R. (1993) Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages. Biochem. J. 290, 165-172
130. Young, I. S., Trouton, T. G., Torney, J. J., McMaster, D., Callender, M. E., and Trimble, E. R. (1994) Antioxidant status and lipid peroxidation in hereditary haemochromatosis. Free Rad. Biol. Med. 16, 393-397
131. Livrea, M. A., Tesoriere, L., Pintaudi, A. M., Calabrese, A., Maggio, A., Freisleben, H. J., D'Arpa, D., D'Anna, R., and Bongiorno, A. (1996) Oxidative stress and antioxidant status in β-thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood 88, 3608-3614
132. Herbert, V. (1994) The antioxidant supplement myth. Am. J. Clin. Nutr. 60, 157-158
133. Kiechl, S., Willeit, J., Egger, G., Poewe, W., and Oberhollenzer, F. (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96, 3300-3307
134. Franco, R. F., Zago, M. A., Trip, M. D., Cate, H., van den Ende, A., Prins, M. H., Kastelein, J. J., and Reitsma, P. H. (1998) Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. Br. J. Haematol. 102, 1172-1175
135. Winterbourn, C. C. (1981) Hydroxyl radical production in body fluids: roles of metal ions, ascorbate and superoxide. Biochem. J. 198, 125-131
136. Minetti, M., Forte, T., Soriani, M., Quarisima, V., Menditto, A., and Ferrari, M. (1992) Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation: no spin-trapping evidence for the hydroxyl radical in iron-overload plasma. Biochem. J. 282, 459-465
137. Collis, C. S., Yang, M., Peach, S. J., Diplock, A. T., and Rice-Evans, C. (1996) The effects of ascorbic acid and iron co-supplementation on the proliferation of 3T3 fibroblasts. Free Rad. Res. 25, 87-93
138. Dabbagh, A. J., and Frei, B. (1995) Human suction blister interstitial fluid prevents metal ion-dependent oxidation of low density lipoprotein by macrophages and in cell-free systems. J. Clin. Invest. 96, 1958-1966
139. Retsky, K. L., and Frei, B. (1995) Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein. Biochim. Biophys. Acta 1257, 279-287
140. Otero, P., Viana, M., Herrera, E., and Bonet, B. (1997) Antioxidant and prooxidant effects of ascorbic acid, dehydroascorbic acid and flavonoids on LDL submitted to different degrees of oxidation. Free Rad. Res. 27, 619-626
141. Retsky, K. L., Chen, K., Zeind, J., and Frei, B. (1999) Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation. Free Rad. Biol. Med. 26, 90-98
142. Tsao, C. S., Leung, P. Y., and Young, M. (1987) Effect of dietary ascorbic acid intake on tissue vitamin C in mice. J. Nutr. 117, 291-297
143. Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., and Cantilena, L. R. (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. U. S. A. 93, 3704-3709
144. Lovstad, R. A. (1987) Copper catalyzed oxidation of ascorbate (vitamin C): inhibitory effect of catalase, superoxide dismutase, serum proteins (ceruloplasmin, albumin, apotransferrin) and amino acids. Int. J. Biochem. 19, 309-313
145. Eiserich, J. P., Hristova, M., Cross, C. E., Jones, A. D., Freeman, B. A., Halliwell, B., and van der Vliet, A. (1998) Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature (London) 391, 393-397
146. Cadet, J., Douki, T., and Ravanat, J. L. (1997) Artifacts associated with the measurement of oxidized DNA bases. Environ. Health Perspect. 105, 1034-1039
147. Tsao, C. S. (1997) An overview of ascorbic acid chemistry and biochemistry. In Vitamin C in Health and Disease (Packer, L., and Fuchs, J., eds) pp. 25-58, Marcel Dekker, Inc., New York
148. Thomas, S. R., Neuzil, J., Mohr, D., and Stocker, R. (1995) Coantioxidants make α-tocopherol an efficient antioxidant for low density lipoprotein. Am. J. Clin. Nutr. 62, 1357S-1364S