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Prospects for the Use of Antioxidant Therapies

Summary

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural antioxidant defences have been found to be defective in many of the same diseases. This has led to suggestions that oxidative damage and therefore disease progression may be retarded by supplementing natural antioxidant defences. Potential antioxidant therapy includes natural antioxidant enzymes and vitamins or synthetic agents with antioxidant activity. Diseases where antioxidant therapy may be beneficial include diabetes mellitus, reperfusion injury, inflammatory diseases and the prevention of chronic processes such as atherosclerosis and carcinogenesis. Further well controlled prospective clinical trials of antioxidants are required to establish the efficacy and tolerability of antioxidant therapy in the treatment of human diseases.

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References

  1. 1.

    Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 2nd ed. Oxford: Clarendon Press, 1989

    Google Scholar 

  2. 2.

    Bast A, Haenen GR, Doelman CJ. Oxidants and antioxidants: state of the art. Am J Med 1991; 91: 2S–13S

    PubMed  CAS  Google Scholar 

  3. 3.

    Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989; 320: 365–76

    PubMed  CAS  Google Scholar 

  4. 4.

    Aust SD, Morehouse LA, Thomas CE. Role of metals in oxygen radical reactions. Free Radic Biol Med 1985; 1: 3

    CAS  Google Scholar 

  5. 5.

    Sevenian A, Hochstein P. Mechanisms and consequences of lipid peroxidation in biological systems. Annu Rev Nutr 1985; 5: 365–75

    Google Scholar 

  6. 6.

    Aruoma OI, Halliwell B, Dizdaroglu M. Iron ion-dependent modification of bases in DNA by the superoxide radical generating system hypoxanthine/xanthine oxidase. J Biol Chem 1989; 264: 13024–8

    PubMed  CAS  Google Scholar 

  7. 7.

    Birnboim HC, Kanabus-Kominska M. The production of DNA strand breaks in human leukocytes by superoxide may involve a metabolic process. Proc Natl Acad Sci USA 1987; 82: 6820–4

    Google Scholar 

  8. 8.

    Scholes RG. Radiation effects on DNA. Br J Radiol 1983; 56: 221–31

    PubMed  CAS  Google Scholar 

  9. 9.

    Greenwald RA. Superoxide dismutase and catalase as therapeutic agents for human diseases: a critical review. Free Radic Biol Med 1990; 8: 201–9

    PubMed  CAS  Google Scholar 

  10. 10.

    Takahashi K, Newberger PE, Cohen HJ. Glutathione peroxidase protein: absence in selenium-deficiency states and correlation with enzymatic activity. J Clin Invest 1986; 77: 1402

    PubMed  CAS  Google Scholar 

  11. 11.

    Parnham MJ, Leyck S, Graf E, et al. The pharmacology of ebselen. Agents Actions 1991; 32: 4–9

    PubMed  CAS  Google Scholar 

  12. 12.

    Stocker R, Frei B. Endogenous antioxidant defences in human blood plasma. In Sies H, editor. Oxidative stress: oxidants and antioxidants. London: Academic Press, 1991

    Google Scholar 

  13. 13.

    Modell B, Letsky EA, Flynn DM, et al. Survival and desferrioxamine in thalassaemia major. BMJ 1982; 284: 1081–4

    PubMed  CAS  Google Scholar 

  14. 14.

    Halliwell B. How to characterize a biological antioxidant. Free Radie Res Commun 1990; 9: 1–32

    CAS  Google Scholar 

  15. 15.

    Packer JE, Slater TF, Wilson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 1979; 278: 737

    PubMed  CAS  Google Scholar 

  16. 16.

    Zimetbaum P, Eder H, Frishman W. Probucol: pharmacology and clinical application. J Clin Pharmacol 1990; 30: 3–6

    PubMed  CAS  Google Scholar 

  17. 17.

    Kagan V, Serbinoa E, Packer L. Generation and recycling of radicals from phenolic antioxidants. Arch Biochem Biophys 1990; 280: 33–9

    PubMed  CAS  Google Scholar 

  18. 18.

    Kalyanaraman B, Darley-Usmar VM, Wood J, et al. Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of low density lipoprotein. J Biol Chem 1992; 267: 6789–95

    PubMed  CAS  Google Scholar 

  19. 19.

    Aruoma OI, Wasil M, Halliwell B, et al. The scavenging of oxidants by sulphasalazine and its metabolites. Biochem Pharmacol 1987; 36: 3739–42

    PubMed  CAS  Google Scholar 

  20. 20.

    Hall ED, Braughler JM. Central nervous system trauma and stroke. Free Radic Biol Med 1989; 6: 303–13

    PubMed  CAS  Google Scholar 

  21. 21.

    Steinke DE, Weir BKA, Findlay JM, et al. A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm. Neurosurgery 1989; 24: 179–86

    PubMed  CAS  Google Scholar 

  22. 22.

    McCord JM. Oxygen-derived free radicals in post-ischaemic tissue injury. N Engl J Med 1985; 312: 159–63

    PubMed  CAS  Google Scholar 

  23. 23.

    Grootveld M, Halliwell B, Mocineuse CP, et al. Action of uric acid, allopurinol, and oxypurinol on the myeloperoxidase-de-rived oxidant hypochlorous acid. Free Radie Res Commun 1987; 4: 69–76

    CAS  Google Scholar 

  24. 24.

    de Jong JW, van der Meer P, Nieukoop AS, et al. Xanthine oxidoreductase activity in perfused hearts of various species, including humans. Circ Res 1990; 67: 770–3

    PubMed  Google Scholar 

  25. 25.

    Steinberg D, Parsatharathy S, Carew TE, et al. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989; 320: 915–24

    PubMed  CAS  Google Scholar 

  26. 26.

    Esterbauer H, Gebicki J, Puhl H, et al. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 1992; 13: 341–90

    PubMed  CAS  Google Scholar 

  27. 27.

    Ylä-Herttuala S, Palinski W, Rosenfield ME, et al. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 1989; 84: 1086–95

    PubMed  Google Scholar 

  28. 28.

    Salonen JT, Yla-Herttuala S, Yamomoto R, et al. Autoantibody against oxidized LDL and progression of carotid atherosclerosis. Lancet 1992; 339: 883–7

    PubMed  CAS  Google Scholar 

  29. 29.

    Reaven PD, Khouw A, Beltz WF, et al. Effect of dietary antioxidant combinations in humans: protection of LDL by vitamin E but not by beta-carotene. Arterioscler Thromb 1993; 13: 590–600

    PubMed  CAS  Google Scholar 

  30. 30.

    Regnström J, Nilsson J, Tornvail P, et al. Susceptibility to low density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 1992; 339: 1183–6

    PubMed  Google Scholar 

  31. 31.

    Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks slowing the progression of atherosclerosis in the WHHL rabbit. Proc Natl Acad Sci USA 1987; 84: 7725

    PubMed  CAS  Google Scholar 

  32. 32.

    Gey KF, Puska P, Jordan P, et al. Inverse correlation between plasma vitamin E and mortality from ischaemic heart disease in cross-cultural epidemiology. Am J Clin Nutr 1991; 53: 326S–34S

    PubMed  CAS  Google Scholar 

  33. 33.

    Riemersma RA, Wood DA, Maclntyre CC, et al. Risk of angina pectoris and plasma concentrations of vitamins A, C, E and carotene. Lancet 1991; 337: 1–5

    PubMed  CAS  Google Scholar 

  34. 34.

    Manson JE, Stampfer MJ, Willett WC, et al. A prospective study of the intake of antioxidant vitamins and incidence of coronary heart disease in women [abstract]. Circulation 1991; 84 Suppl. 3: 2168

    Google Scholar 

  35. 35.

    Bolton-Smith C, Woodward M, Tunstall-Pedoe H. The Scottish Heart Health Study: dietary intake by food frequency questionnaire and odds ratios for coronary heart disease risk. Eur J Clin Nutr 1992; 46: 85–93

    PubMed  CAS  Google Scholar 

  36. 36.

    Kardinaal AFM, Kok FJ, Ringstad J, et al. Antioxidants in adipose tissue and risk of myocardial infarction: the Euramic study. Lancet 1993; 342: 1379–84

    PubMed  CAS  Google Scholar 

  37. 37.

    Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993; 328: 1450–6

    PubMed  CAS  Google Scholar 

  38. 38.

    Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary heart disease in women. N Engl J Med 1993; 328: 1446–9

    Google Scholar 

  39. 39.

    Elinder LS, Walldius G. Antioxidants and atherosclerosis progression. Curr Opin Lipidol 1994; 5: 265–8

    PubMed  CAS  Google Scholar 

  40. 40.

    Hertog MGL, Feskens EJM, Hollman PCH, et al. Dietary antioxidant flavanoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993; 342: 1007–11

    PubMed  CAS  Google Scholar 

  41. 41.

    Frankel EN, Kanner J, German JB, et al. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993; 341: 454–7

    PubMed  CAS  Google Scholar 

  42. 42.

    Maxwell SRJ, Cruickshank A, Thorpe GHG. Red wine and serum antioxidant activity. Lancet 1994; 344: 193–4

    PubMed  CAS  Google Scholar 

  43. 43.

    Keaney JF, Gaziano JM, Xu A, et al. Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 1994; 93: 844–51

    PubMed  Google Scholar 

  44. 44.

    ISIS-3 (Thid International Study of Infarct Survival) Collaborative Group. A randomised comparison of streptokinase vs plasminogen activator vs antistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet 1992; 339: 753–70

    Google Scholar 

  45. 45.

    Goldhaber JI, Weiss JN. Oxygen free radicals and cardiac reperfusion abnormalities. Hypertension 1992; 20: 118–27

    PubMed  CAS  Google Scholar 

  46. 46.

    Braunwald E, Kloner RA. The stunned myocardium — prolonged post-ischemic ventricular dysfunction. Circulation 1982; 66: 1146–9

    PubMed  CAS  Google Scholar 

  47. 47.

    Bernier M, Hearse DJ, Manning AS. Reperfusion-induced arrhythmias and oxygen-derived free radicals. Circ Res 1986; 58: 331–40

    PubMed  CAS  Google Scholar 

  48. 48.

    Blann A, Midgley H, Burrows G, et al. Free radicals, antioxidants and endothelial cell damage after percutaneous transluminal coronary angioplasty. Coron Artery Dis 1993; 4: 905–10

    PubMed  CAS  Google Scholar 

  49. 49.

    Davies SW, Randajayalan K, Wickens DG, et al. Lipid peroxidation associated with successful thrombolysis. Lancet 1990; 335: 741–3

    PubMed  CAS  Google Scholar 

  50. 50.

    Coghlan JG, Flitter WD, Holley AE, et al. Detection of free radicals and cholesterol hydroperoxides from the coronary sinus of man during percutaneous transluminal coronary angioplasty. Free Radic Res Commun 1991; 14: 409–17

    PubMed  CAS  Google Scholar 

  51. 51.

    Kloner RA, Przyklenk K, Whittaker R Deleterious effects of oxygen radicals in ischemia/reperfusion: resolved and unresolved issues. Circulation 1989; 80: 1115–25

    PubMed  CAS  Google Scholar 

  52. 52.

    Opie LH. Reperfusion injury and its pharmacological modification. Circulation 1989; 80: 1049–92

    PubMed  CAS  Google Scholar 

  53. 53.

    Bolli R, McCay PB. Use of spin traps in intact animals undergoing myocardial ischaemia/reperfusion: a new approach to assessing the role of oxygen radicals in myocardial stunning. Free Radic Res Commun 1990; 9: 169–80

    PubMed  CAS  Google Scholar 

  54. 54.

    Fellstrom BC, Larsson E. Pathogenesis and treatment perspectives of chronic graft rejection (CVR). Immunol Rev 1993; 134: 83–98

    PubMed  CAS  Google Scholar 

  55. 55.

    Land W, Schneeberger H, Schleibner S, et al. The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants. Transplantation 1994; 57: 211–7

    PubMed  CAS  Google Scholar 

  56. 56.

    Blumhardt G, Neuhaus P. Does antioxidant treatment have a role in liver transplantation? Klin Wochenschr 1991; 69: 1105–8

    PubMed  CAS  Google Scholar 

  57. 57.

    Currin RT, Toole JG, Thurman RG, et al. Evidence that Carolina rinse solution protects sinusoidal endothelial cells against reperfusion injury after cold ischaemic storage of rat liver. Transplantation 1990; 50: 1076–8

    PubMed  CAS  Google Scholar 

  58. 58.

    Slakey DP, Roza AM, Pieper GM, et al. Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy. Transplantation 1993; 56: 1305–9

    PubMed  CAS  Google Scholar 

  59. 59.

    Goode HF, Webster NR, Howdle PD, et al. Reperfusion injury, antioxidants and haemodynamics during orthotopic liver transplantation. Hepatology 1994; 19: 354–9

    PubMed  CAS  Google Scholar 

  60. 60.

    Barnett AH. Pathogenesis of diabetic microangiopathy: an overview. Am J Med 1991; 90 Suppl. 6A: 67–73

    Google Scholar 

  61. 61.

    Bierman EL. Atherogenesis in diabetes. Arterioscler Thromb 1992; 12: 647–56

    PubMed  CAS  Google Scholar 

  62. 62.

    Jennings PE, Jones AF, Florkowski CM, et al. Increased diene conjugates in patients with diabetic microangiopathy. Diabet Med 1987; 4: 452–6

    PubMed  CAS  Google Scholar 

  63. 63.

    Jones AF, Jennings PE, Wakefield A, et al. The fluorescence of serum proteins in patients with and without retinopathy. Diabet Med 1988; 5: 547–51

    PubMed  CAS  Google Scholar 

  64. 64.

    Hunt SV, Dean RP, Wolff SP. Hydroxyl radical production and autooxidative glycosylation: glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J 1988; 256: 205–15

    PubMed  CAS  Google Scholar 

  65. 65.

    Hunt JV, Wolff SP. Oxidative glycation and free radical production: a causal mechanism of diabetic complications. Free Radic Res Commun 1991; 12-13: 115–23

    PubMed  CAS  Google Scholar 

  66. 66.

    Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end-products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318: 1315–21

    PubMed  CAS  Google Scholar 

  67. 67.

    Cerami A, Vlassara H, Brownlee M. Role of advanced glycosylation products in complications of diabetes. Diabetes Care 1988; 11 Suppl. 1: 73–79

    PubMed  Google Scholar 

  68. 68.

    Jones AF, Winkles JW, Jennings PE, et al. Serum antioxidant activity in diabetes mellitus. Diabetes Res 1988; 7: 89–92

    PubMed  CAS  Google Scholar 

  69. 69.

    Sinclair AJ, Girling AJ, Gray L, et al. Disturbed handling of ascorbic acid in diabetic patients with and without diabetic microangiopathy using high dose ascorbate supplementation. Gerontology 1992; 38: 268–74

    PubMed  CAS  Google Scholar 

  70. 70.

    Stringer MD, Gorog PG, Freeman A, et al. Lipid peroxides and atherosclerosis. BMJ 1989; 298: 281–4

    PubMed  CAS  Google Scholar 

  71. 71.

    Stolba P, Hatle K, Krnakova K, et al. Effects of ascorbic acid on non-enzymatic glycation of serum proteins in vitro and in vivo [abstract]. Diabetologia 1987; 30: 529

    Google Scholar 

  72. 72.

    Ceriello A, Giugliano D, Quatraro A, et al. A preliminary note on inhibiting effect of alpha-tocopherol (vitamin E) on protein glycation. Diabete Metab 1988; 14: 40–2

    PubMed  CAS  Google Scholar 

  73. 73.

    Ceriello A, Giugliano D, Quatraro A, et al. Vitamin E reduction of protein glycosylation in diabetes: new prospects for prevention of diabetic complications? Diabetes Care 1991; 14: 68–72

    PubMed  CAS  Google Scholar 

  74. 74.

    Ceriello A, Quatraro A, Giugliano D. New insights on non-enzymatic glycosylation may lead to therapeutic approaches for the prevention of diabetic complications. Diabet Med 1992; 9: 297–9

    PubMed  CAS  Google Scholar 

  75. 75.

    Babior BM. Oxygen-dependent microbial killing by phagocytes. N Engl J Med 1978; 298: 659–68, 721-5

    PubMed  CAS  Google Scholar 

  76. 76.

    Halliwell B, Hoult JRS, Blake DR. Oxidants, inflammation and anti-inflammatory drugs. FASEB J 1988; 2: 501–18

    Google Scholar 

  77. 77.

    Henson PE, Johnston RB. Tissue injury in inflammation: oxidants, proteinases, and cationic proteins. J Clin Invest 1987; 79: 669–74

    PubMed  CAS  Google Scholar 

  78. 78.

    Biemond P, Van Eijk HG, Swaak AJG, et al. Iron mobilisation from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes: possible mechanism in inflammation diseases. J Clin Invest 1984; 73: 1576–9

    PubMed  CAS  Google Scholar 

  79. 79.

    Winrow VR, Winyard PG, Morris CJ, et al. Free radicals in inflammation: secondary messengers and mediators of tissue distinction. Br Med Bull 1993; 49: 506–22

    PubMed  CAS  Google Scholar 

  80. 80.

    Yamada T, Grisham MB. Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochenschr 1991; 69: 988–94

    PubMed  CAS  Google Scholar 

  81. 81.

    Schoenberg MH, Buchler M, Beger HG. The role of oxygen radicals in experimental acute pancreatitis. Free Radic Biol Med 1992; 12: 515–22

    PubMed  CAS  Google Scholar 

  82. 82.

    Uden S, Bilton D, Nathan L, et al. Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial. Aliment Pharmacol Ther 1990; 4: 357–71

    PubMed  CAS  Google Scholar 

  83. 83.

    Peto R, Doll R, Buckley DJ, et al. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981; 290: 201–8

    PubMed  CAS  Google Scholar 

  84. 84.

    Byers T, Perry J. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Annu Rev Nutr 1992; 12: 139–59

    PubMed  CAS  Google Scholar 

  85. 85.

    Bendich A, Olson JA. Biological actions of carotenoids. FASEB J 1989; 3: 1927–32

    PubMed  CAS  Google Scholar 

  86. 86.

    Stahelin HB, Gey L-F, Eichholzer M, et al. Beta-carotene and cancer prevention: the Basel Study. Am J Clin Nutr 1991; 53: 2655–95

    Google Scholar 

  87. 87.

    Hennekens CH, Stampfer MJ, Willett W. Micronutrients and cancer chemoprevention. Cancer Detect Prev 1984; 7: 147–58

    PubMed  CAS  Google Scholar 

  88. 88.

    Hennekens CH. Micronutrients and cancer prevention. N Engl J Med 1986; 315: 1288–9

    PubMed  CAS  Google Scholar 

  89. 89.

    Srinivas L, Shalini VK. DNA damage by smoke: protection by tumeric and other inhibitors of ROS. Free Radic Biol Med 1991; 11: 277–83

    PubMed  CAS  Google Scholar 

  90. 90.

    Pacht ER, Davis WB. Failure of high dose vitamin E to correct caeruloplasmin ferroxidase deficiency in cigarette smokers. Am Rev Resp Dis 1990; 142: 1063–7

    PubMed  CAS  Google Scholar 

  91. 91.

    Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994; 330: 1029–35

    Google Scholar 

  92. 92.

    Bulpitt CJ. Vitamin C and blood pressure. J Hypertens 1990; 8: 1071–5

    PubMed  CAS  Google Scholar 

  93. 93.

    Ceriello A, Giugliano D, Quatraro A, et al. Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects. Clin Sci 1991; 81: 739–42

    PubMed  CAS  Google Scholar 

  94. 94.

    Nakazono K, Watanabe N, Matsuno K, et al. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 1991; 88: 10045–8

    PubMed  CAS  Google Scholar 

  95. 95.

    Gryglewski RJ, Palmer RMJ, Moneada S. Superoxide ion is involved in the breakdown of endothelium-derived relaxing factor. Nature 1986; 320: 454–6

    PubMed  CAS  Google Scholar 

  96. 96.

    Ruboyi GM, Vanhouette PM. Superoxide anions and hyperoxide inactivate endothelium-derived relaxing factor. Am J Physiol 1986; 250: H822–7

    Google Scholar 

  97. 97.

    Redl H, Gasser H, Hallstrom S, et al. Involvement of oxygen radicals in shock and organ failure. In: Sies H, editor. Oxidative stress: oxidants and antioxidants. London: Academic Press, 1991: 595–616

    Google Scholar 

  98. 98.

    Youn YK, LaLonde C, Demling R. Use of antioxidant therapy in shock and trauma. Circ Shock 1991; 35: 245–9

    PubMed  CAS  Google Scholar 

  99. 99.

    Goode HF, Webster NR. Free radicals and antioxidants in sepsis. Crit Care Med 1993; 21: 1770–6

    PubMed  CAS  Google Scholar 

  100. 100.

    Repine JE. Scientific perspectives on adult respiratory distress syndrome. Lancet 1992; 339: 466–72

    PubMed  CAS  Google Scholar 

  101. 101.

    Halliwell B, Gutteridge JMC. Oxygen radicals and the nervous system. Trends Neurosci 1985; 8: 22–6

    CAS  Google Scholar 

  102. 102.

    Hall ED, Braughler JM, McCall JM. Antioxidant effects in brain and spinal cord injury. J Neurotrauma 1992; 9 Suppl. 1: S165–72

    PubMed  Google Scholar 

  103. 103.

    Koller WC. Initiating the treatment of Parkinson’s disease. Neurology 1992; 42 Suppl. 1: 33–8

    PubMed  CAS  Google Scholar 

  104. 104.

    Olanow CW. A rationale for monoamine oxidase inhibition as neuroprotective therapy for Parkinson’s disease. Mov Disord 1993; 8 Suppl. 1: S1–7

    PubMed  Google Scholar 

  105. 105.

    Buhl R, Jaffe HA, Holroyd KJ, et al. Systemic glutathione deficiency in symptom-free HIV-seropositive patients. Lancet 1989; 2: 1294–6

    PubMed  CAS  Google Scholar 

  106. 106.

    Halliwell B, Cross CE. Reactive oxygen species, antioxidants and the acquired immunodeficiency syndrome. Arch Int Med 1991; 151: 29–31

    CAS  Google Scholar 

  107. 107.

    Roederer M, Staal FJT, Raju PA, et al. Cytokine stimulated human immunodeficiensy virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci USA 1990; 87: 4884–8

    PubMed  CAS  Google Scholar 

  108. 108.

    Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992; 340: 1124–7

    PubMed  CAS  Google Scholar 

  109. 109.

    Witt EH, Reznick AZ, Viguie CA, et al. Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 1992; 122: 766–73

    PubMed  CAS  Google Scholar 

  110. 110.

    Davies KJA, Quinantilha AT, Brooks GA, et al. Free radical and tissue damage produced by exercise. Biochem Biophys Res Commun 1982; 107: 1198–205

    PubMed  CAS  Google Scholar 

  111. 111.

    Viguie CA, Frei B, Shigenaga MK, et al. Antioxidant status and indexes of oxidative stress during consecutive days of exercise. J Appl Physiol 1993; 75: 566–72

    PubMed  CAS  Google Scholar 

  112. 112.

    Robertson JD, Maugham RJ, Duthie GG, et al. Increased blood antioxidant systems of runners in response to training load. Clin Sci 1991; 80: 611–8

    PubMed  CAS  Google Scholar 

  113. 113.

    Maxwell SRJ, Jakeman P, Thomason H, et al. Changes in plasma antioxidant status during eccentric exercise and the effect of vitamin supplementation. Free Radie Res Commun 1993; 19: 191–202

    CAS  Google Scholar 

  114. 114.

    Jakeman P, Maxwell SRJ. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol 1993; 67: 426–30

    CAS  Google Scholar 

  115. 115.

    Jackson MJ, Edwards RH. Free radicals and trials of antioxidant therapy in muscle disorders. Adv Exp Biol Med 1990; 264: 485–91

    CAS  Google Scholar 

  116. 116.

    Howard LJ. The neurologic syndrome of vitamin E deficiency: laboratory and electrophysiological assessment. Nutr Rev 1990; 48: 169–77

    Google Scholar 

  117. 117.

    Chiswick M, Gladman G, Sinha S, et al. Vitamin E supplementation and periventricular haemorrhage in the newborn. Am J Clin Nutr 1991; 53: 370S–2S

    PubMed  CAS  Google Scholar 

  118. 118.

    Moison RMW, Palinckx JJS, Roest M, et al. Induction of lipid peroxidation of pulmonary surfactant by plasma of preterm babies. Lancet 1993; 341: 79–82

    PubMed  CAS  Google Scholar 

  119. 119.

    Varma S. Scientific basis for the medical therapy of cataracts by antioxidants. Am J Clin Nutr 1991; 53: 335S–45S

    PubMed  CAS  Google Scholar 

  120. 120.

    Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake and cataract extraction in women: a prospective study. BMJ 1992; 305: 335–9

    PubMed  CAS  Google Scholar 

  121. 121.

    Richer SP. Is there a prevention and treatment trategy for macular degeneration? J Am Optom Ass 1993; 64: 838–50

    CAS  Google Scholar 

  122. 122.

    Mathews-Roth MM. Photoprotection by carotenoids. FASEB J 1987; 46: 1890–3

    CAS  Google Scholar 

  123. 123.

    Fuchs J, Huflejt M, Rothfuss L, et al. Dermatologic antioxidant therapy may be warranted to prevent ultraviolet-induced skin damage. Adv Exp Med Biol 1990; 264: 533–6

    PubMed  CAS  Google Scholar 

  124. 124.

    Flannagan RJ, Meredith TJ. Use of N-acetylcysteine in clinical toxicology. Am J Med 1991; 91: S131–9

    Google Scholar 

  125. 125.

    Cohen GM, Doherty M. Free radical mediated cell toxicity by redox cycling chemicals. Br J Cancer 1987; 55 Suppl. 8: 46–52

    CAS  Google Scholar 

  126. 126.

    Gerli G, Locatelli GF, Mongiat R, et al. Erythrocyte antioxidant activity, serum caeruloplasmin, and trace element levels in subjects with alcoholic liver disease. Am J Clin Pathol 1992; 97: 614–8

    PubMed  CAS  Google Scholar 

  127. 127.

    Butcher GP, Rhodes JM, Walker R, et al. The effect of antioxidant supplementation on a serum marker of free radical activity and abnormal serum biochemistry in alcoholic patients admitted for detoxification. J Hepatol 1993; 19: 105–9

    PubMed  CAS  Google Scholar 

  128. 128.

    Ganguly PK. Antioxidant therapy in congestive heart failure: is there any advantage? J Inter Med 1991; 229: 205–8

    CAS  Google Scholar 

  129. 129.

    Mortensen SA. Perspectives on therapy of cardiovascular diseases with co-enzyme Q10 (ubiquinone). Clin Invest 1993; 71: S116–23

    CAS  Google Scholar 

  130. 130.

    McMurray J, Chopra M, McLay J, et al. Free radical activity in chronic heart failure and the effect of Captopril. Br Heart J 1989; 61: 457–8

    Google Scholar 

  131. 131.

    Richard MJ, Arnaud J, Jurkovitz C, et al. Trace element and lipid peroxidation abnormalities in patients with chronic renal failure. Nephron 1991; 57: 10–15

    PubMed  CAS  Google Scholar 

  132. 132.

    Paul JL, Man NK, Moatti N, et al. Membrane phospholipid peroxidation in renal insufficiency and chronic haemodialysis. Nephrologie 1991; 12: 4–7

    PubMed  CAS  Google Scholar 

  133. 133.

    Davidge ST, Hubel CA, Brayden RD, et al. Sera antioxidant activity in uncomplicated and pre-eclamptic pregnancies. Obstet Gynaecol 1992; 79: 897–901

    CAS  Google Scholar 

  134. 134.

    Guarnieri C, Zucchelli G, Bernardi F, et al. Enhanced superoxide production with no change of the antioxidant activity in gingival fluid of patients with chronic adult periodontitis. Free Radic Res Commun 1991; 15: 11–6

    PubMed  CAS  Google Scholar 

  135. 135.

    Crystal RG. Oxidants and respiratory tract epithelial injury: pathogenesis and strategies for therapeutic intervention. Am J Med 1991; 91 Suppl. 3C: 39S–44S

    PubMed  CAS  Google Scholar 

  136. 136.

    Clemens MR. Antioxidant therapy in haematological disorders. Adv Exp Biol Med 1990; 264: 423–33

    CAS  Google Scholar 

  137. 137.

    Rice-Evans CA, Diplock AT. Current status of antioxidant therapy. Free Radic Biol Med 1993; 15: 77–96

    PubMed  CAS  Google Scholar 

  138. 138.

    Rangan U, Bulkley GB. Prospects for treatment of free radical-mediated tissue injury. Br Med Bull 1993; 49: 700–18

    PubMed  CAS  Google Scholar 

  139. 139.

    Weglicki WB, Mak IT, Simic MG. Mechanisms of cardiovascular drugs as antioxidants. J Mol Cell Cardiol 1990; 22: 1199

    PubMed  CAS  Google Scholar 

  140. 140.

    Hearse DJ. Prospects for antioxidant therapy in cardiovascular medicine. Am J Med 1991; 91: 118S–21S

    PubMed  CAS  Google Scholar 

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Correspondence to Simon R. J. Maxwell.

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Maxwell, S.R.J. Prospects for the Use of Antioxidant Therapies. Drugs 49, 345–361 (1995). https://doi.org/10.2165/00003495-199549030-00003

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Keywords

  • Probucol
  • Antioxidant Therapy
  • Ebselen
  • Free Radical Activity
  • Oxypurinol