Environmental Health and Preventive Medicine

, Volume 13, Issue 2, pp 102–108

Selenium: its role as antioxidant in human health

Review

Abstract

Selenium (Se) is an essential trace element, and its low status in humans has been linked to increased risk of various diseases, such as cancer and heart disease. In recent years, Se research has attracted tremendous interest because of its important role in antioxidant selenoproteins for protection against oxidative stress initiated by excess reactive oxygen species (ROS) and reactive nitrogen species (NOS). The synthesis of selenoproteins requires a unique incorporation of amino acid selenocysteine (Sec) into proteins directed by the UGA codon, which is also a termination codon. Interest in Se research has led to the discovery of at least 30 selenoproteins; however, the biochemical functional roles of some of these selenoproteins are still unknown. Besides in the form of selenoproteins, Se can exist in many different chemical forms in biological materials either as organic Se compounds, such as selenomethionine and dimethylselenide, and inorganic selenites and selenates. In foods, Se is predominantly present as selenomethionine, which is an important source of dietary Se in humans, and also as a chemical form that is commonly used for Se supplements in clinical trials. Concern for potential deficiency diseases associated with low Se status has led to the establishment of the recommended daily requirements for Se in many countries. However, excess Se intakes through supplementation and its potential misuse as health therapy could also pose a risk of adverse health effects if its use is not properly regulated.

Keywords

Antioxidants Oxidative stress Selenium Selenoenzymes Selenoproteins 

References

  1. 1.
    Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharm. 2003;57:134–44.CrossRefGoogle Scholar
  2. 2.
    Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, et al. Characterization of mammalian selenoproteomes. Science. 2003;300:1439–43.PubMedCrossRefGoogle Scholar
  3. 3.
    Mix H, Lobanov AV, Gladyshev VN. SECIS elements in the coding regions of selenoproteins transcripts are functional in higher eukaryotes. Nucleic Acids Res. 2007;35:414–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Birringer M, Pilawa S, Flohe L. Trends in selenium biochemistry. Nat Prod Rep. 2002;19:693–718.PubMedCrossRefGoogle Scholar
  5. 5.
    Allmang C, Krol A. Selenoprotein synthesis: UGA does not end the story. Biochimie. 2006;88:1561–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Brenneisen P, Steinbrenner H, Sies H. Selenium, oxidative stress, health aspects. Mol Aspects Med. 2005;26:256–67.PubMedCrossRefGoogle Scholar
  7. 7.
    Suzuki KT, Kurasaki K, Okazaki N, Ogra Y. Selenosugar, trimethylselenonium among urinary Se metabolites: dose- and age-related changes. Toxicol Appl Pharmacol. 2005;206:1–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Klotz LO, Kroncke KD, Buchczyk DP, Sies H. Role of copper, zinc, selenium, tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr. 2003;133:1448S–51S.PubMedGoogle Scholar
  9. 9.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals, antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160:1–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem. 2000;267:6102–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Das KC, Das CK. Thioredoxin, a singlet oxygen quencher and hydroxyl radical scavenger: redox independent functions. Biochem Biophys Res Commun. 2000;277:443–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Nordberg J, Arner ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med. 2001;31:1287–312.PubMedCrossRefGoogle Scholar
  13. 13.
    Gromer S, Urig S, Becker K. The thioredoxin system-from science to clinic. Med Res Rev. 2004;24:40–89.PubMedCrossRefGoogle Scholar
  14. 14.
    Steinbrenner H, Alili L, Bilgic E, Sies H, Brenneisen P. Involvement of selenoprotein P in protection of human astrocytes from oxidative damage. Free Radic Biol Med. 2006;40:1513–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Steinbrenner H, Bilgic E, Alili L, Sies H, Brenneisen P. Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity. Free Radic Res. 2006;40:936–43.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R, et al. Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions. Am J Pathol. 2007;170:1108–20.PubMedCrossRefGoogle Scholar
  17. 17.
    Furman C, Rundlof AK, Larigauderie G, Jaye M, Bricca G, Copin C, et al. Thioredoxin reductase 1 is upregulated in atherosclerotic plaques: specific induction of the promoter in human macrophages by oxidized low-density lipoproteins. Free Radic Biol Med. 2004;37:71–85.PubMedCrossRefGoogle Scholar
  18. 18.
    Dhingra S, Bansal MP. Attenuation of LDL receptor gene expression by selenium deficiency during hypercholesterolemia. Mol Cell Biochem. 2006;282:75–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Traulsen H, Steinbrenner H, Buchczyk DP, Klotz LO, Sies H. Selenoprotein P protects low-density lipoprotein against oxidation. Free Radic Res. 2004;38:123–8.PubMedCrossRefGoogle Scholar
  20. 20.
    World CJ, Yamawaki H, Berk BC. Thioredoxin in the cardiovascular system. J Mol Med. 2006;84:997–1003.PubMedCrossRefGoogle Scholar
  21. 21.
    Alissa EM, Bahijri SM, Ferns GA. The controversy surrounding selenium and cardiovascular disease: a review of the evidence. Med Sci Monit. 2003;9:RA9–18.PubMedGoogle Scholar
  22. 22.
    Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr. 2006;84:762–73.PubMedGoogle Scholar
  23. 23.
    Shamberger RJ, Gunsch MS, Willis CE, McCoormack LJ. Selenium and heart disease. II-Selenium and other trace metal intakes and heart disease in 25 Countries. In: Hemphill DD editor. Trace substances in environmental health–XII. Missouri: University of Missouri. 1978. p. 48–52.Google Scholar
  24. 24.
    Shamberger RJ, Willis CE, McCoormack LJ. Selenium and heart disease. III-Blood selenium and heart disease mortality in 19 States. In: Hemphill DD editor. Trace substances in environmental health–XIII. Missouri: University of Missouri. 1979. p. 59–63.Google Scholar
  25. 25.
    Huttunen JK. Selenium and cardiovascular diseases – an update. Biomed Environ Sci. 1997;10:220–6.PubMedGoogle Scholar
  26. 26.
    Stranges S, Marshall JR, Trevisan M, Natarajan R, Donahue RP, Combs GF, et al. Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial. Am J Epidemiol. 2006;163:694–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Venardos KM, Kaye DM. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. Curr Med Chem. 2007;14:1539–49.PubMedCrossRefGoogle Scholar
  28. 28.
    Jekell A, Hossain A, Alehagen U, Dahlstrom U, Rosen A. Elevated circulating levels of thioredoxin and stress in chronic heart failure. Eur J Heart Fail. 2004;6:883–90.PubMedGoogle Scholar
  29. 29.
    Tanguy S, Toufektsian MC, Besse S, Ducros V, De Leiris J, Boucher F. Dietary selenium intake affects cardiac susceptibility to ischaemia/reperfusion in male senescent rats. Age Ageing. 2003;32:273–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Venardos K, Harrison G, Headrick J, Perkins A. Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion. J Trace Elem Med Biol. 2004;18:81–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Venardos K, Ashton K, Headrick J, Perkins A. Effects of dietary selenium on post-ischemic expression of antioxidant mRNA. Mol Cell Biochem. 2005;270:131–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Lymbury R, Venardos K, Perkins AV. Effect of sodium selenite-enriched reperfusion solutions on rat cardiac ischemia reperfusion injury. Biol Trace Elem Res. 2006;114:197–206.PubMedCrossRefGoogle Scholar
  33. 33.
    Sakurai T, Kanayama M, Shibata T, Itoh K, Kobayashi A, Yamamoto M, et al. Ebselen, a seleno-organic antioxidant, as an electrophile. Chem Res Toxicol. 2006;19:1196–204.PubMedCrossRefGoogle Scholar
  34. 34.
    Baljinnyam E, Hasebe N, Morihira M, Sumitomo K, Matsusaka T, Fujino T, et al. Oral pretreatment with ebselen enhances heat shock protein 72 expression and reduces myocardial infarct size. Hypertens Res. 2006;29:905–13.PubMedCrossRefGoogle Scholar
  35. 35.
    Lapchak PA, Zivin JA. Ebselen, a seleno-organic antioxidant, is neuroprotective after embolic strokes in rabbits: synergism with low-dose tissue plasminogen activator. Stroke. 2003;34:2013–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, et al. Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke. 1998;29:12–7.PubMedGoogle Scholar
  37. 37.
    Zhao R, Holmgren A. A novel antioxidant mechanism of ebselen involving ebselen diselenide, a substrate of mammalian thioredoxin and thioredoxin reductase. J Biol Chem. 2002;277:39456–62.PubMedCrossRefGoogle Scholar
  38. 38.
    Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional prevention of cancer study group. JAMA. 1996;276:1957–63.PubMedCrossRefGoogle Scholar
  39. 39.
    Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst. 1998;90:1219–24.PubMedCrossRefGoogle Scholar
  40. 40.
    Ghadirian P, Maisonneuve P, Perret C, Kennedy G, Boyle P, Krewski D, et al. A case-control study of toenail selenium and cancer of the breast, colon, and prostate. Cancer Detect Prev. 2000;24:305–13.PubMedGoogle Scholar
  41. 41.
    Allen NE, Morris JS, Ngwenyama RA, Key TJ. A case-control study of selenium in nails and prostate cancer risk in British men. Br J Cancer. 2004;90:1392–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Peters U, Foster CB, Chatterjee N, Schatzkin A, Reding D, Andriole GL, et al. Serum selenium and risk of prostate cancer-a nested case-control study. Am J Clin Nutr. 2007;85:209–17.PubMedGoogle Scholar
  43. 43.
    Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? Eur J Cancer. 2006;42:2463–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM Jr, Kristal AR, et al. Designing the selenium and vitamin E cancer prevention trial (SELECT). J Natl Cancer Inst. 2005;97:94–102.PubMedCrossRefGoogle Scholar
  45. 45.
    Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, et al. SELECT: the selenium and vitamin E cancer prevention trial: rationale and design. Prostate Cancer Prostatic Dis. 2000;3:145–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364:1219–28.PubMedCrossRefGoogle Scholar
  47. 47.
    Brinkman M, Buntinx F, Muls E, Zeegers MP. Use of selenium in chemoprevention of bladder cancer. Lancet Oncol. 2006;7:766–74.PubMedCrossRefGoogle Scholar
  48. 48.
    Rayman MP. Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc. 2005;64:527–42.PubMedCrossRefGoogle Scholar
  49. 49.
    McKenzie RC, Arthur JR, Beckett GJ. Selenium and the regulation of cell signaling, growth, and survival: molecular and mechanistic aspects. Antioxid Redox Signal. 2002;4:339–51.PubMedCrossRefGoogle Scholar
  50. 50.
    Whanger PD. Selenium and its relationship to cancer: an update dagger. Br J Nutr. 2004;91:11–28.PubMedCrossRefGoogle Scholar
  51. 51.
    El-Bayoumy K. The protective role of selenium on genetic damage and on cancer. Mutat Res. 2001;475:123–39.PubMedGoogle Scholar
  52. 52.
    Lu J, Jiang C. Selenium and cancer chemoprevention: hypotheses integrating the actions of selenoproteins and selenium metabolites in epithelial and non-epithelial target cells. Antioxid Redox Signal. 2005;7(11–12):1715–27.PubMedCrossRefGoogle Scholar
  53. 53.
    Waters DJ, Shen S, Glickman LT, Cooley DM, Bostwick DG, Qian J, et al. Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model. Carcinogenesis. 2005;26:1256–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Karunasinghe N, Ryan J, Tuckey J, Masters J, Jamieson M, Clarke LC, et al. DNA stability and serum selenium levels in a high-risk group for prostate cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:391–7.PubMedGoogle Scholar
  55. 55.
    Battin EE, Perron NR, Brumaghim JL. The central role of metal coordination in selenium antioxidant acitivity. Inorg Chem. 2006;45:499–501.PubMedCrossRefGoogle Scholar
  56. 56.
    Papp LV, Lu J, Holmgren A, Khanna KK. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal. 2007;9:775–806.PubMedCrossRefGoogle Scholar
  57. 57.
    Beck MA. Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 2001;20:384S–8S.PubMedGoogle Scholar
  58. 58.
    Beck M. Selenium, viral infections. In: Hatfield DL, Berry MJ, Gladyshev VN, editors. Selenium – its molecular biology and role in human health, New York: Springer; 2006. p. 287–98.Google Scholar
  59. 59.
    Broome CS, McArdle F, Kyle JA, Andrews F, Lowe NM, Hart CA, et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr. 2004;80:154–62.PubMedGoogle Scholar
  60. 60.
    Baum MK, Campa A. Role of selenium in HIV/AIDS. In: Hatfield DL, Berry MJ, Gladyshev VN, editors. Selenium – its molecular biology and role in human health, New York: Springer; 2006. p. 299–310.Google Scholar
  61. 61.
    McKenzie RC, Beckett GJ, Arthur JR. Effects of selenium on immunity and aging. In: Hatfield DL, Berry MJ, Gladyshev VN editors. Selenium – its molecular biology and role in human health, New York: Springer; 2006. p. 287–98.Google Scholar
  62. 62.
    Gartner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab. 2002;87:1687–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Duntas LH. The role of selenium in thyroid autoimmunity and cancer. Thyroid. 2006;16:455–60.PubMedCrossRefGoogle Scholar
  64. 64.
    Kohrle J. Selenium and the control of thyroid hormone metabolism. Thyroid. 2005;15:841–53.PubMedCrossRefGoogle Scholar
  65. 65.
    Vanderpas JB, Contempre B, Duale NL, Deckx H, Bebe N, Longombe AO, et al. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am J Clin Nutr. 1993;57:271S–5S.PubMedGoogle Scholar
  66. 66.
    Contempre B, Le Moine O, Dumont JE, Denet J-F, Many MC. Selenium deficiency and thyroid fibrosis. A key role of macrophases and transforming growth factor β (TGF- β). Mol Cell Endocrin. 1996;124:7–15.CrossRefGoogle Scholar
  67. 67.
    Dumitrescu AM, Liao XH, Abdullah MS, Lado-Abeal J, Majed FA, Moeller LC, et al. Mutations in SECIS BP2 result in abnormal thyroid hormone metabolism. Nat Genet. 2005;37:1247–52.PubMedCrossRefGoogle Scholar
  68. 68.
    Tinggi U, Reilly C, Patterson CM. Determination of selenium in foodstuffs using spectrofluorometry and hydride generation atomic absorption spectrometry. J Food Comp Anal. 1992;5:269–80.CrossRefGoogle Scholar
  69. 69.
    Tinggi U. Determination of selenium in meat products by hydride generation atomic absorption spectrophotometry. J AOAC Int. 1999;82:364–7.PubMedGoogle Scholar
  70. 70.
    Reilly C. Selenium in food and health. New York: Springer; 2006.Google Scholar
  71. 71.
    Thomson CD. Selenium and iodine intakes and status in New Zealand and Australia. Br J Nutr. 2004;91(5):661–72.PubMedCrossRefGoogle Scholar
  72. 72.
    Eurola MH, Ekholm PI, Ylinen ME, Koivistoinen PE, Varo PT. Selenium in Finnish foods after beginning the use of selenate-supplemented fertilisers. J Sci Food Agric. 1991;56:57–70.CrossRefGoogle Scholar
  73. 73.
    Rayman MP. The use of high-selenium yeast to raise selenium status: how does it measure up? Br J Nutr. 2004;92:557–73.PubMedCrossRefGoogle Scholar
  74. 74.
    Lyons GH, Judson GJ, Ortiz-Monasterio I, Genc Y, Stangoulis JC, Graham RD. Selenium in Australia: selenium status and biofortification of wheat for better health. J Trace Elem Med Biol. 2005;19:75–82.PubMedCrossRefGoogle Scholar
  75. 75.
    Broadley MR, White PJ, Bryson RJ, Meacham MC, Bowen HC, Johnson SE, et al. Biofortification of UK food crops with selenium. Proc Nutr Soc. 2006;65:169–81.PubMedCrossRefGoogle Scholar
  76. 76.
    Lobinski R, Edmonds J, Suzuki K, Uden P. Species-selective determination of selenium compounds in biological materials. Pure Appl Chem. 2000;72:447–61.CrossRefGoogle Scholar
  77. 77.
    Dumont E, Vanhaecke F, Cornels R. Selenium speciation from food source to metabolites: a critical review. Anal Bioanal Chem. 2006;385:1304–23.PubMedCrossRefGoogle Scholar
  78. 78.
    British Nutrition Foundation. Selenium and Health. London: The British Nutrition Foundation; 2001Google Scholar
  79. 79.
    Levander OA, Burk RF. Update of human dietary standards for selenium. In: Hatfield DL, Berry MJ, Gladyshev VN, editors. Selenium – its molecular biology and role in human health, Springer: New York; 2006. p. 399–410.Google Scholar
  80. 80.
    Department of Health and Ageing. Nutrient Reference Values for Australia and New Zealand. Canberra: Commonwealth of Australia; 2006.Google Scholar
  81. 81.
    Tinggi U. Essentiality and toxicity of selenium and its status in Australia: a review. Toxicol Lett. 2003;137:103–10.PubMedCrossRefGoogle Scholar
  82. 82.
    Tinggi U. Selenium toxicity, its adverse health effects. In: Preed V, Watson R editors. Reviews in food and nutrition toxicity. Boca Raton: CRC Press; 2005. p. 29–55.Google Scholar
  83. 83.
    See KA, Lavercombe PS, Dillon J, Ginsberg R. Accidental death from acute selenium poisoning. Med J Aust. 2006;185:388–9.Google Scholar

Copyright information

© The Japanese Society for Hygiene 2008

Authors and Affiliations

  1. 1.Centre for Public Health SciencesQueensland Health Scientific ServicesCoopers PlainsAustralia

Personalised recommendations