Transition Metal Chemistry

, Volume 37, Issue 2, pp 127–134 | Cite as

Redox active metal-induced oxidative stress in biological systems

  • Klaudia JomovaEmail author
  • Stanislav Baros
  • Marian ValkoEmail author


A number of studies performed on biological systems have shown that redox-active metals such as iron and copper as well as other transition metals can undergo redox cycling reactions and produce reactive free radicals termed also reactive oxygen species (ROS) or reactive nitrogen species (RNS). The most representative examples of ROS and RNS are the superoxide anion radical and nitric oxide, respectively, both playing a dual role in biological systems. At low/moderate concentrations of ROS and RNS, they can be involved in many physiological roles such as defense against infectious agents, involvement in a number of cellular signaling pathways and other important biological processes. On the other hand, at high concentrations, ROS and RNS can be important mediators of damage to biomolecules involving DNA, membrane lipids, and proteins. One of the most damaging ROS occurring in biological systems is the hydroxyl radical formed via the decomposition of hydrogen peroxide catalyzed by traces of iron, copper and other metals (the Fenton reaction). The hydroxyl radical is known to react with the DNA molecule, forming 8-OH-Guanine adduct, which is a good biomarker of oxidative stress of an organism and a potential biomarker of carcinogenesis. This review discusses the role of iron and copper in uncontrolled formation of ROS leading to various human diseases such as cancer, cardiovascular disease, and neurological disorders (Alzheimer’s disease and Parkinson’s disease). A discussion is devoted to the various protective antioxidant networks against the deleterious action of free radicals. Metal-chelation therapy, which is a modern pharmacotherapy used to chelate redox-active metals and remove toxic metals from living systems to avoid metal poisoning, is also discussed.


Fenton Reaction Reactive Nitrogen Species Chelation Therapy Copper Chelator Clioquinol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by Scientific Grant Agency (VEGA Projects #1/0856/11 and #1/0289/12) and Research and Development Agency of the Slovak Republic (Contracts APVV-0202-10 and APVV-0339-10).


  1. 1.
    Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. University Science Books, Mill Valley, CAGoogle Scholar
  2. 2.
    Holm RH, Kennepohl P, Solomon EI (1996) Chem Rev 96:2239–2314CrossRefGoogle Scholar
  3. 3.
    Bertini I, Cavallaro G (2008) J Biol Inorg Chem 13:3–14CrossRefGoogle Scholar
  4. 4.
    Valko M, Morris H, Cronin MTD (2005) Curr Med Chem 12:1161–1208CrossRefGoogle Scholar
  5. 5.
    Buettner GR (1993) Arch Biochem Biophys 300:535–543CrossRefGoogle Scholar
  6. 6.
    Prousek J (2007) Pure Appl Chem 79:2325–2338CrossRefGoogle Scholar
  7. 7.
    Liochev SI, Fridovich I (2002) Redox Rep 7:55–57CrossRefGoogle Scholar
  8. 8.
    Kell DB (2010) Arch Toxicol 84:825–889CrossRefGoogle Scholar
  9. 9.
    Kell DB (2009) BMC Med Genomics 2:2CrossRefGoogle Scholar
  10. 10.
    Jomova K, Valko M (2011) Toxicology 283:65–87CrossRefGoogle Scholar
  11. 11.
    Jomova K, Valko M (2011) Curr Pharm Des 17:3460–3473CrossRefGoogle Scholar
  12. 12.
    Schafer FQ, Buettner GR (2001) Free Radic Biol Med 30:1191–1212CrossRefGoogle Scholar
  13. 13.
    Liochev SI, Fridovich I (1994) Free Radic Biol Med 16:29–33CrossRefGoogle Scholar
  14. 14.
    Kakhlon O, Cabantchik ZI (2002) Free Radic Biol Med 33:1037–1046CrossRefGoogle Scholar
  15. 15.
    Gaetke LM, Chow CK (2003) Toxicology 189:147–163CrossRefGoogle Scholar
  16. 16.
    Kuo YM, Zhou B, Cosco D, Gitschier J (2001) Proc Natl Acad Sci USA 98:6836–6841CrossRefGoogle Scholar
  17. 17.
    Cadet J, Douki T, Ravanat JL (2011) Mutat Res 711:3–12CrossRefGoogle Scholar
  18. 18.
    Cai X, Pan N, Zou G (2007) Biometals 20:1–11CrossRefGoogle Scholar
  19. 19.
    Udenfriend S, Clark CT, Axelrod J, Brodie BB (1954) J Biol Chem 208:731–739Google Scholar
  20. 20.
    Suh J, Zhu BZ, Frei B (2003) Free Radic Biol Med 34:1306–1314CrossRefGoogle Scholar
  21. 21.
    Shigenaga MK, Gimeno CJ, Ames BN (1989) Proc Natl Acad Sci USA 86:9697–9701CrossRefGoogle Scholar
  22. 22.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Chem Biol Interact 160:1–40CrossRefGoogle Scholar
  23. 23.
    Stadtman ER (2004) Curr Med Chem 11:1105–1112Google Scholar
  24. 24.
    Stoltzfus R (2001) J Nutr 131:565S–567SGoogle Scholar
  25. 25.
    Toyokuni S (1996) Free Radic Biol Med 20:553–566CrossRefGoogle Scholar
  26. 26.
    Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, OxfordGoogle Scholar
  27. 27.
    LaMarca BD, Gilbert J, Granger JP (2008) Hypertension 51:982–988CrossRefGoogle Scholar
  28. 28.
    Marnett LJ (1999) Mutat Res 424:83–95CrossRefGoogle Scholar
  29. 29.
    Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M (2005) World J Gastroenterol 11:403–406Google Scholar
  30. 30.
    Valko M, Morris H, Mazúr M, Rapta P, Bilton RF (2001) Biochim Biophys Acta 1527:161–166CrossRefGoogle Scholar
  31. 31.
    Jomova K, Vondrakova D, Lawson M, Valko M (2010) Mol Cell Biochem 345:91–104CrossRefGoogle Scholar
  32. 32.
    Zhu X, Castellani RJ, Moreira PI, Aliev G, Shenk JC, Siedlak SL, Harris PL, Fujioka H, Sayre LM, Szweda PA, Szweda LI, Smith MA, Perry G (2012) Free Radic Biol Med. doi: 10.1016/j.freeradbiomed.2011.11.004
  33. 33.
    Bush AI (2003) Trends Neurosci 26:207–214CrossRefGoogle Scholar
  34. 34.
    Varadarajan S, Yatin S, Aksenova M, Butterfield DA (2000) J Struct Biol 130:184–208CrossRefGoogle Scholar
  35. 35.
    Butterfield DA, Sultana R (2011) J Amino Acids (article ID 198430)Google Scholar
  36. 36.
    Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI (1999) J Biol Chem 274:37111–37116CrossRefGoogle Scholar
  37. 37.
    Jenner P (2003) Ann Neurol 53:S26–S36CrossRefGoogle Scholar
  38. 38.
    Chinta SJ, Andersen JK (2008) Biochim Biophys Acta 1780:1362–1367CrossRefGoogle Scholar
  39. 39.
    Andersen JK (2004) Nature Med 10:S18–S25CrossRefGoogle Scholar
  40. 40.
    Bamonti F, Fulgenzi A, Novembrino C, Ferrero ME (2011) Biometals 24:1093–1098CrossRefGoogle Scholar
  41. 41.
    Bendova P, Mackova E, Haskova P, Vavrova A, Jirkovsky E, Sterba M, Popelova O, Kalinowski DS, Kovarikova P, Vavrova K, Richardson DR, Simunek T (2010) Chem Res Toxicol 23:1105–1114CrossRefGoogle Scholar
  42. 42.
    Dairam A, Fogel R, Daya S, Limson JL (2008) J Agric Food Chem 56:3350–3356CrossRefGoogle Scholar
  43. 43.
    Kalinowski DS, Richardson DR (2007) Chem Res Toxicol 20:715–720CrossRefGoogle Scholar
  44. 44.
    Welch KD, Davis TZ, Van Eden ME, Aust SD (2002) Free Radic Biol Med 32:577–583CrossRefGoogle Scholar
  45. 45.
    Braun V, Endriss F (2007) Biometals 20:219–231CrossRefGoogle Scholar
  46. 46.
    Le CT, Hollaar L, Van der Valk EJ, Van der Laarse A (1994) J Mol Cell Cardiol 26:877–887CrossRefGoogle Scholar
  47. 47.
    Bush AI (2002) Neurobiol Aging 23:1031–1038CrossRefGoogle Scholar
  48. 48.
    Horwitz LD, Sherman NA, Kong YN (1998) Proc Natl Acad Sci 95:5263–5268CrossRefGoogle Scholar
  49. 49.
    De Vries B, Walter SJ, Von Bonsdorff L (2004) Transplantation 77:669–675CrossRefGoogle Scholar
  50. 50.
    Kontoghiorghes GJ (2006) Hemoglobin 30:183–200CrossRefGoogle Scholar
  51. 51.
    Wang T, Guo Z (2006) Curr Med Chem 13:525–537CrossRefGoogle Scholar
  52. 52.
    Khan G, Merajver S (2009) Expert Opin Investig Drugs 18:541–548CrossRefGoogle Scholar
  53. 53.
    Gupte A, Mumper RJ (2009) Cancer Treat Rev 35:32–46CrossRefGoogle Scholar
  54. 54.
    Hyman LM, Stephenson CJ, Dickens MG, Shimizu KD, Franz KJ (2010) Dalton Trans 39:568–576Google Scholar
  55. 55.
    Pierre JL, Baret P, Serratrice G (2003) Curr Med Chem 10:1077–1084CrossRefGoogle Scholar
  56. 56.
    Bush AI (2008) J Alzheimers Dis 15:223–240Google Scholar
  57. 57.
    Miklos D, Segla P, Palicova M, Kopcova M, Melnik M, Valko M, Glowiak T, Korabik M, Mrozinski J (2001) Polyhedron 20:1867–1874CrossRefGoogle Scholar
  58. 58.
    Moncol J, Kalinakova B, Svorec J, Kleinova M, Koman M, Hudecova D, Melnik M, Mazur M, Valko M (2004) Inorg Chim Acta 357:3211–3222CrossRefGoogle Scholar
  59. 59.
    Shimada H, Takahashi M, Shimada A, Okawara T, Yasutake A, Imamura Y, Kiyozumi M (2005) Toxicol Appl Pharmacol 202:59–67CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of Natural SciencesConstantine The Philosopher UniversityNitraSlovakia
  2. 2.Faculty of Chemical and Food TechnologySlovak Technical UniversityBratislavaSlovakia

Personalised recommendations