Non-Chelation Dependent Redox Actions of Desferrioxamine

  • Ben-Zhan Zhu
  • Ronit Har-El
  • Nahum Kitrossky
  • Mordechai Chevion
Part of the NATO ASI Series book series (NSSA, volume 296)


Desferrioxamine (DFO) has been widely used as a specific iron chelator. In this study, the non-chelation dependent redox actions of DFO were demonstrated. The protection by DFO against DNA scission caused by tetrachlorohydroquinone arises from a reaction between tetrachlorosemiquinone radical and DFO which yields a DFO nitroxide free radical. DFO was also found to enhance dechlorination of tetrachloro-1,4-benzoquinone. These results suggest two additional mechanisms through which DFO might have effects on biological oxidation reactions.


HEPES Buffer Iron Chelator Hydroxamic Acid Semiquinone Radical Prooxidant Action 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blobstein, S. H., Grady, R. W., Meshnick, S. R.and Cerami, A., 1978, Hydroxamic acid oxidation - pharmacological considerations, Biochem. Pharmacol. 27: 2939 – 2945.CrossRefGoogle Scholar
  2. Borg, D. C.and Schaich, K. M., 1986, Prooxidant action of desferrioxamine: Fenton-like production of hydroxyl radicals by reduced ferrioxamine, J. Free Rad. Biol. Med. 2: 237 – 243.CrossRefGoogle Scholar
  3. Carstens, C. P., Blum, J. K. and Witte, 1., 1990, The role of hydroxyl radicals in tetrachloro-hydroquinone induced DNA strand break formation in PM2 DNA and human fibroblasts, Chem-Biol. Interact. 74: 305 – 314.CrossRefGoogle Scholar
  4. Chung, N.and Aust, S. D, 1995, Veratryl alcohol-mediated indirect oxidation of pentachlorophenol by lignin peroxidase, Arch. Biochem. Biophys. 322: 143 – 148.Google Scholar
  5. Cooper, C. E., Green, E. S. R., Rice-Evans, C. A., Davies, M. J. and Wrigglesworth J. M., 1994, A hydrogen-donating monohydroxamate scavenges ferryl myoglobin radicals, Free Rad. Res. 20: 219 – 227.CrossRefGoogle Scholar
  6. Dahlhaus, M., Almstadt, E. and Appel, K. E., 1994, The pentachlorophenol metabolite tetrachloro-p-hydroquinone induces the formation of 8-hydroxy-2-deoxyguanosine in liver DNA of male B6C3F1 mice, Toxicol. Lett. 74: 265 – 274.CrossRefGoogle Scholar
  7. Dahlhaus, M., Almstadt, E., Henschke, P., Luttgert, S. and Appel, K. E., 1995, Induction of 8-hydroxy-2-deoxyguanosine and single strand breaks in DNA of V79 cells by tetrachloro-p-hydroquinone, Mutation Res. 329: 29 – 36.CrossRefGoogle Scholar
  8. Dahlhaus, M., Almstadt, E., Henachke, P., Luttgert, S. and Appel, K. E., 1996, Oxidative DNA lesions in V79 cells mediated by pentachlorophenol metabolites, Arch. Toxicol. 70: 457 – 460.CrossRefGoogle Scholar
  9. Darley-Usmar, V. M., Hersey, A. and Garland, L. G., 1989, A method for comparative assessment of antioxidant as peroxyl radical scavengers, Biochem. Pharmacol. 38: 1645 – 1649.CrossRefGoogle Scholar
  10. Davies, M. J., Donkor, R., Dunster, C. A., Gee, C. A., Jonas, S. and Wilson, R. L., 1987, Desferrioxamine and superoxide radicals. Formation of an enzyme-damaging nitroxide, Biochem. J. 246: 725 – 729.Google Scholar
  11. De Matteis, F., Dawson, S. J. and Gibbs, A. H., 1993, Two pathways of iron-catalyzed oxidation of bilirubin: effect of desferrioxamine and Trolox, and comparison with microsomal oxidation, Free Rad. Biol. Med. 15: 301 – 309.CrossRefGoogle Scholar
  12. Denicola, A., Souza, J. M., Gatti, R. M., Augusto, O. and Radi, R., 1995, Desferrioxamine inhibition of the hydroxyl radical-like reactivity of peroxynitrite: Role of hydroxamic groups, Free Rad. Biol. Med. 19: 11 – 19.CrossRefGoogle Scholar
  13. Dzwigaj, S. and Pezerat, H., 1995, H. Singlet oxygen-trapping reaction as a method of ‘0, detection: role of some reducing agents, Free Rad. Res. 23: 103 – 115.CrossRefGoogle Scholar
  14. Eaton, J. W., 1996, Iron: the essential poison, Redox Report 2: 215.Google Scholar
  15. Freedman, N. H., Boyden, M., Talor, M. and Skarf, B., 1988, Neurotoxicity associated with deferoxamine therapy, Toxicology 49: 283 – 290.CrossRefGoogle Scholar
  16. Gabutti, V. and Piga, A., 1996, Results of long-term iron-chelating therapy, Acta Haematol. 95: 26 – 36.CrossRefGoogle Scholar
  17. Giardina, P. J. and Grady, R. W., 1995, Chelation therapy in 13-thalassemia: the benefits and limitations of desferrioxamine, Seminars Hematol. 32: 304 – 312.Google Scholar
  18. Graf, E., Mahoney, J. R., Bryant, R. G.and Eaton, J. W., 1984, Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site, J. Biol. Chem. 259: 3620 – 3624.Google Scholar
  19. Grankvist, K. and Marklund, S. L., 1983, Opposite effects of two metal-chelators on alloxan-induced diabetes in mice, Life Sci. 33: 2535 – 2540.CrossRefGoogle Scholar
  20. Green, E. S. R., Rice-Evans, H., Rice-Evans, P., Davies, M. J., Salah, N. and Rice-Evans, C. A., 1993, The efficacy of monohydroxamates as free radical scavenging agents compared with di-and tri-hydroxamates, Biochem. Pharmacol. 45: 357 – 366.CrossRefGoogle Scholar
  21. Goldstein, S. and Czapski, G., 1990, A reinvestigation of the reaction of desferrioxamine with superoxide radicals. A pulse radiolysis study, Free Rad. Res. Comm. 11: 231 – 240.CrossRefGoogle Scholar
  22. Gutteridge, J. M. C., Richmond, R. and Halliwell, B., 1979, Inhibition of the iron-catalyzed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine, Biochem. J. 184: 469 – 472.Google Scholar
  23. Halliwell, B., 1985, Use of desferrioxamine as a “probe” for the iron-dependent formation of hydroxyl radicals. Evidence for a direct reaction between desferal and the superoxide radical, Biochem. Pharmacol. 34: 229 – 233.CrossRefGoogle Scholar
  24. Halliwell, B., 1989, Protection against tissue damage in vivo by desferrioxamine: What is its mechanism of action?, Free Rad. Biol. Med. 7: 645 – 651.Google Scholar
  25. Hammel, K. E. and Tardone, P. J., 1988, The oxidative 4-dechlorination of polychlorinated phenols is catalyzed by extracelluar fungal lignin peroxidases, Biochemistry 27: 6563 – 6568.CrossRefGoogle Scholar
  26. Hartley, A., Davies, M. J. and Rice-Evans, C. A., 1990, Desferrioxamine as a chain breaking antioxidant in sickle cell membrane, FEBS Lett. 264: 145 – 148.CrossRefGoogle Scholar
  27. Hershko, C., Pinson, A. and Link, G., 1996, Prevention of anthracycline cardiotoxicity by iron chelation, Acta Haematol. 95: 87 – 92.CrossRefGoogle Scholar
  28. Hoe, S., Rowley, D. A. and Halliwell, B., 1982, Reactions of ferrioxamine and desferrioxamine with the hydroyl radical, Chem-Biol. Interact. 41: 75 – 81.CrossRefGoogle Scholar
  29. Kanner, J. and Harel, S., 1987, Desferrioxamine as an eletron donor. Inhibition of membrance lipid peroxidation initiated by H2O,-activated myoglobin, Free Rad. Res. Comm. 3: 309 – 317.CrossRefGoogle Scholar
  30. Keberle, H., 1964, The biochemistry of desferrioxamine and its relation to iron metabolism, Ann. N. Y. Acad. Sci. 119: 758 – 768.CrossRefGoogle Scholar
  31. Klebanoff, S. J., Waltersdorph, A. M., Michel, B. R. and Rosen, H., 1989, Oxygen-based free radical generation by ferrous iron and deferoxamine, J. Biol. Chem. 264: 19765 – 19771.Google Scholar
  32. Kontoghiorghes, G. J., 1995, Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs, Toxicol. Lett. 80: 1 – 18.CrossRefGoogle Scholar
  33. Koppenol, W. H. and Butler, J., 1985, Energetics in interconversion reactions of oxyradicals, Adv. Free Rad. Biol. Med. 1: 91 – 131.CrossRefGoogle Scholar
  34. Koss, G., Losekam, M., Seidel, J., Steinbach, K. and Koransky, W., 1987, Inhibitory effect of tetrachloro-p-hydroquinone and other metabolites of hexachlorobenzene on hepatic uroporphyrinogen decarboxylase activity with reference to the role of glutathione, Ann. N.Y Acad. Sci. 514: 148 – 159.CrossRefGoogle Scholar
  35. Lee, Y. S. and Wurster, R. D., 1995, Deferoxamine-induced cytotoxicity in human neuronal cell lines: Protection by free radical scavengers, Toxicol. Lett. 78: 67 – 71.CrossRefGoogle Scholar
  36. Marx, J. J. M. and Van Asbeck, B. S., 1996, Use of iron chelators in preventing hydroxyl radical damage: adult respiratory distress syndrome as an experimental model for the pathophysiology and treatment of oxygenradical-mediated tissue damage, Acta Haematol. 95: 49 – 62.CrossRefGoogle Scholar
  37. Mclaren, G. D., Muir, W. A. and Kellermeyer, R. W., 1983, Iron overload disorders: natural history, pathogenesis, diagnosis and therapy, CRC Crit. Rev. Clin. Lab. Sci. 19: 205 – 265.CrossRefGoogle Scholar
  38. Mordente, A., Meucci, E., Miggiano, G. A. D. and Martorana, G. E., 1990, Prooxidant action of desferrioxamine: enhancement of alkaline phosphatase inactivation by interaction with ascorbate system, Arch. Biochem. Biophys. 277: 234 – 240.CrossRefGoogle Scholar
  39. Morehouse, K. M., Flitter, W. D. and Mason, R. P., 1987, The enzymatic oxidation of desferal to a nitroxide free radical, FEBS Lett. 222: 246 – 250.CrossRefGoogle Scholar
  40. Naito, S., Ono, Y., Somiya, I., Inoue, S., Ito, K., Yamamoto, K. and Kawanishi, S., 1994, Role of active oxygen species in DNA damage by pentachlorophenol metabolites, Mutation Res. 310: 79 – 88.CrossRefGoogle Scholar
  41. Nohl, H., Jordan, W. and Youngman R. J., 1986, Quinones in biology: function in electron transfer and oxygen activation, Adv. Free Rad. Biol. Med. 2: 211 – 279.CrossRefGoogle Scholar
  42. Nohl, H. and Jordan, W., 1987, The involement of biological quinones in the formation of hydroxyl radicals via the Haber-Weiss reaction, Biorg. Chem. 15: 374 – 382.CrossRefGoogle Scholar
  43. Powis, G., 1989, Free radical formation by antitumor quinones, Free Rad. Biol. Med. 6: 63 – 101.CrossRefGoogle Scholar
  44. Rice-Evans, C. A., Okunade, G.and Khan, R., 1989, The suppression of iron release from activated myoglobin by physiological electron donors and desferrioxamine, Free Rad. Res. Comm. 7: 45 – 54.Google Scholar
  45. Ruckdeschel, G. and Renner, G., 1986, Effects of pentachlorophenol and some of its known and possible metabolites on fungi, Appl. Environ. Microbiol. 51: 1370 – 1372.Google Scholar
  46. Samokyszyn, V. M., Freeman, J. P., Maddipati, K. R. and Lloyd, R. V., 1995, Peroxidase-catalyzed oxidation of pentachlorophenol, Chem. Res. Toxicol. 8: 349 – 355.CrossRefGoogle Scholar
  47. San, D. H., Kazunga, C., Charles, M. J., Pavlovich, J. G. and Aitken, M. D., 1995, Decomposition of tetrachloro1,4-benzoquinone (P-chloranil) in aqueous solution, Environ. Sci. Technol. 29: 2735 – 2740.CrossRefGoogle Scholar
  48. Seiler, J. P., 1991, Pentachlorophenol, Mutation Res. 257: 27 – 47.CrossRefGoogle Scholar
  49. Shimoni, E., Armon, R. and Neeman, I., 1994, Antioxidant properties of deferoxamine, J. Am. Oil Chem. Soc. 71: 641 – 644.CrossRefGoogle Scholar
  50. Soriani, M., Mazzuca, S., Quaresima, V. and Minetti, M., 1993, Oxidation of desferrioxamine to nitroxide free radical by activated human neutrophils, Free Rad. Biol. Med. 14: 589 – 599.CrossRefGoogle Scholar
  51. Van Ommen, B., Adang, A. E. P., Brader, L., Posthumus, M. A., Muller, F. and Van Bladeren, P. J., 1986, The microsomal metabolism of hexachlorobenzene. Biochem. Pharmacol. 35: 3233 – 3238.CrossRefGoogle Scholar
  52. Van Ommen, B., Adang, A., Muller, F. and Van Bladeren, P. J., 1986, The microsomal metabolism of pentachlorophenol and its covalent binding to protein and DNA, Chem-Biot. Interact. 60: 1 – 11.CrossRefGoogle Scholar
  53. Van Reyk, D. M. and Dean, R. T., 1996, The iron-selective chelator desferal can reduce chelated copper, Free Rad. Res. 24: 55 – 60.CrossRefGoogle Scholar
  54. Waidyanatha, S., McDonald, T. A., Lin, P. H. and Rappaport, S. M., 1994, Measurement of hemoglobin and albumin adducts of tetrachrobenzoquinone, Chem. Res. Toxicol. 7: 463 – 468.CrossRefGoogle Scholar
  55. Witte, I., Juhl, U. and Butte, W., 1985, DNA-damaging properties and cytotoxicity in human fibroblasts of tetrachlorohydroquinone, a pentachlorophenol metabolite, Mutation Res. 145: 71 – 75.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Ben-Zhan Zhu
    • 1
  • Ronit Har-El
    • 1
  • Nahum Kitrossky
    • 1
  • Mordechai Chevion
    • 1
    • 2
  1. 1.Department of Cellular BiochemistryHebrew University, Hadassah Schools of Medicine and Dental MedicineJerusalemIsrael
  2. 2.Department of Cellular BiochemistryHebrew University-Hadassah Medical SchoolJerusalemIsrael

Personalised recommendations