Preferences help
enabled [disable] Abstract
Number of results
2000 | 47 | 4 | 951-962
Article title

Generation of ·OH initiated by interaction of Fe2+ and Cu+ with dioxygen; comparison with the Fenton chemistry.

Title variants
Languages of publication
Iron and copper toxicity has been presumed to involve the formation of hydroxyl radical (·OH) from H2O2 in the Fenton reaction. The aim of this study was to verify that Fe2+-O2 and Cu+-O2 chemistry is capable of generating ·OH in the quasi physiological environment of Krebs-Henseleit buffer (KH), and to compare the ability of the Fe2+-O2 system and of the Fenton system (Fe2+ + H2O2) to produce ·OH. The addition of Fe2+ and Cu+ (0-20 μM) to KH resulted in a concentration-dependent increase in ·OH formation, as measured by the salicylate method. While Fe3+ and Cu2+ (0-20 μM) did not result in ·OH formation, these ions mediated significant ·OH production in the presence of a number of reducing agents. The ·OH yield from the reaction mediated by Fe2+ was increased by exogenous Fe3+ and Cu2+ and was prevented by the deoxygenation of the buffer and reduced by superoxide dismutase, catalase, and desferrioxamine. Addition of 1 μM, 5 μM or 10 μM Fe2+ to a range of H2O2 concentrations (the Fenton system) resulted in a H2O2-concentration-dependent rise in ·OH formation. For each Fe2+ concentration tested, the ·OH yield doubled when the ratio [H2O2]:[Fe2+] was raised from zero to one. In conclusion: (i) Fe2+-O2 and Cu+-O2 chemistry is capable of promoting ·OH generation in the environment of oxygenated KH, in the absence of pre-existing superoxide and/or H2O2, and possibly through a mechanism initiated by the metal autoxidation; (ii) The process is enhanced by contaminating Fe3+ and Cu2+; (iii) In the presence of reducing agents also Fe3+ and Cu2+ promote the ·OH formation; (iv) Depending on the actual [H2O2]:[Fe2+] ratio, the efficiency of the Fe2+-O2 chemistry to generate ·OH is greater than or, at best, equal to that of the Fe2+-driven Fenton reaction.
Physical description
  • Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warszawa, Poland
  • Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warszawa, Poland
  • 1. Halliwell, B. & Gutteridge, J.M.C. (1990) Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol. 186, 1-85.
  • 2. Keyer, K. & Imlay, J.A. (1996) Superoxide accelerates DNA damage by elevating free-iron levels. Proc. Natl. Acad. Sci. U.S.A. 93, 13635-13640.
  • 3. Yue Qian, S. & Buettner, G.R. (1999) Iron and dioxygen chemistry is an important route to initiation of biologic free radical oxidations: An electron paramagnetic resonance spin trapping study. Free Radic. Biol. Med. 26, 1447-1456.
  • 4. Rush, J.D. & Koppenol, W.H. (1986) Oxidizing intermediates in the reaction of ferrous EDTA with hydrogen peroxide. J. Biol. Chem. 261, 6730-6733.
  • 5. Wink, D.A., Nims, R.W., Saavedra, J.E., Utermahlen, W.E., Jr. & Ford, P.C. (1994) The Fenton oxidation mechanism: Reactivities of biologically relevant substrates with two oxidizing intermediates differ from those predicted for the hydroxyl radical. Proc. Natl. Acad. Sci. U.S.A. 91, 6604-6608.
  • 6. Miller, D.M., Buettner, G.R. & Aust, S.D. (1990) Transition metals as catalysts of autoxidation reactions. Free Radic. Biol. Med. 8, 95-108.
  • 7. Kosaka, H. & Shiga, T. (1993) Spin trapping study of superoxide production in ferrous ion oxidation. Free Radical Res. Commun. 19, S63-S69.
  • 8. Biaglow, J.E. & Kachur, A.V. (1997) The generation of hydroxyl radicals in the reaction of molecular oxygen with polyphosphate complexes of ferrous ions. Radiat. Res. 148, 181-187.
  • 9. Kachur, A.V., Tuttle, S.W. & Biaglow, J.E. (1998) Autoxidation of ferrous ion complexes: A method for the generation of hydroxyl radicals. Radiat. Res. 150, 475-482.
  • 10. Floyd, R.A., Watson, J.J. & Wong, P.K. (1984) Sensitive assay of hydroxyl radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products. J. Biochem. Biophys. Methods 10, 221-235.
  • 11. Obata, T. & Yamanaka, Y. (1996) Effect of iron (II) on the generation of hydroxyl free radicals in rat myocardium. Biochem. Pharmacol. 51, 1411-1413.
  • 12. Hunt, J.V., Dean, R.T. & Wolff, S.P. (1988) Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem. J. 256, 205-212.
  • 13. Kaur, H., Whiteman, M. & Halliwell, B. (1997) Peroxynitrite-dependent aromatic hydroxylation and nitration of salicylate and phenylalanine. Is hydroxyl radical involved? Free Radic. Res. 26, 71-82.
  • 14. Gower, J., Healing, G. & Green, C. (1989) Measurement by HPLC of desferrioxamine-available iron in rabbit kidneys to assess the effect of ischemia on the distribution of iron within the total pool. Free Radical Res. Commun. 5, 291-299.
  • 15. Voogd, A., Sluiter, W., Vaneijk, H.G. & Koster, J.F. (1992) Low molecular weight iron and the oxygen paradox in isolated rat hearts. J. Clin. Invest. 90, 2050-2055.
  • 16. Chevion, M., Jiang, Y.D., Harel, R., Berenshtein, E., Uretzky, G. & Kitrossky, N. (1993) Copper and iron are mobilized following myocardial ischemia possible predictive criteria for tissue injury. Proc. Natl. Acad. Sci. U.S.A. 90, 1102-1106.
  • 17. Coudray, C., Pucheu, S., Boucher, F., Arnaud, J., Deleiris, J. & Favier, A. (1994) Effect of ischemia/reperfusion sequence on cytosolic iron status and its release in the coronary effluent in isolated rat heart. Biol. Trace Elem Res. 41, 69-75.
  • 18. Mączewski, M. & Beręsewicz, A. (2000) The role of endothelin, protein kinase C, and free radicals in the mechanism of the post-ischemic endothelial dysfunction in guinea-pig hearts. J. Mol. Cell. Cardiol. 32, 297-310.
  • 19. Minotti, G. & Aust, S.D. (1992) Redox cycling of iron and lipid peroxidation. Lipids 27, 219-225.
  • 20. Maestre, P., Lambs, L., Thouvenot, J.P. & Berthon, G. (1994) Copper-ligand interactions and physiological free radical processes. 2. Influence of Cu2+ ions on Cu+-driven .OH generation and comparison with their effects on Fe2+-driven ·OH production. Free Radical Res. 20, 205-218.
  • 21. Halliwell, B. (1985) Use of desferrioxamine as a probe' for iron-dependent formation of hydroxyl radicals. Evidence for a direct reaction between desferal and the superoxide radical. Biochem. Pharmacol. 34, 229-233.
  • 22. Sutton, H.C. & Winterbourn, C.C. (1989) On the participation of higher oxidation states of iron and copper in Fenton reactions. Free Radic. Biol. Med. 6, 53-60.
  • 23. Nayini, N.R., White, B.C., Aust, S.D., Huang, R.R., Indrieri, R.J., Evans, A.T., Bialek, H., Jacobs, W.A. & Komara, J. (1985) Post resuscitation iron delocalization and malondialdehyde production in the brain following prolonged cardiac arrest. J. Free Radic. Biol. Med. 1, 111-116.
  • 24. Bolli, R. (1991) Oxygen-derived free radicals and myocardial reperfusion injury. Cardiovasc. Drugs Ther. 5, 249-268.
  • 25. Bauza, G., Lemoyec, L. & Eugene, M. (1995) pH regulation during ischaemia-reperfusion of isolated rat hearts, and metabolic effects of 2,3-butanedione monoxime. J. Mol. Cell. Cardiol. 27, 1703-1713.
  • 26. Harris, D.C. & Aisen, P. (1973) Facilitation of Fe(II) autoxidation by Fe(III) complexing agents. Biochim. Biophys. Acta 329, 156-158.
  • 27. Welch, G.N. & Loscalzo, J. (1998) Homocysteine and atherothrombosis. N. Engl. J. Med. 338, 1042-1050.
  • 28. Nappi, A.J. & Vass, E. (1997) Comparative studies of enhanced iron-mediated production of hydroxyl radical by glutathione, cysteine, ascorbic acid, and selected catechols. Biochim. Biophys. Acta 1336, 295-302.
  • 29. Rehman, A., Collis, C.S., Yang, M., Kelly, M., Diplock, A.T., Halliwell, B. & Riceevans, 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.
  • 30. Podmore, I.D., Griffiths, H.R., Herbert, K.E., Mistry, N., Mistry, P. & Lunec, J. (1998) Vitamin C exhibits pro-oxidant properties. Nature 392, 559.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.