Biometals

, Volume 14, Issue 2, pp 159–170

Structure-activity relationship studies of protective function of nitroxides in Fenton system

  • Jolanta Glebska
  • Lukasz Pulaski
  • Krzysztof Gwozdzinski
  • Janusz Skolimowski
Article

Abstract

The aim of this study was to evaluate the effect of piperidine nitroxides and their amine precursors on deoxyribose oxidation in the Fenton system. Protecting activity of nitroxides was found to be concentration-dependent and strongly influenced by ring substituents, while secondary amines did not provide any protection. The reported results suggest a mechanism of nitroxide action through iron oxidation rather than through direct scavenging of hydroxyl radicals. Moreover, presented data point to the danger of interference of nitroxides during the TBARS assay procedure.

deoxyribose Fenton reaction nitroxides structure-activity relationship TBARS 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antosiewicz J, Popinigis J, Wozniak M, Damiani E, Carloni P, Greci L. 1995 Effects of indolinic and quinolinic aminoxyls on protein and lipid peroxidation of rat liver microsomes. Free Radic Biol Med 18, 913–917Google Scholar
  2. Aruoma OI. 1994 Deoxyribose assay for detecting hydroxyl radicals. Methods Enzymol 233, 57–66.Google Scholar
  3. Aruoma OI, Chaudhary SS, Grootveld M, Halliwell B. 1989 Binding of iron(II) ions to the pentose sugar 2-deoxyribose. J Inorg Biochem 35, 149–155.Google Scholar
  4. Bar-On P, Mohsen M, Zhang R, Feigin E, Chevion M, Samuni A. 1999 Kinetics of Nitroxide Reaction with Iron(II). J Am Chem Soc 121, 8070–8073.Google Scholar
  5. Charloux C, Paul M, Loisance D, Astier A. 1995 Inhibition of hydroxyl radical production by lactobionate, adenine, and tempol. Free Radic Biol Med 19, 699–704.Google Scholar
  6. Damiani E, Kalinska B, Canapa A et al. 2000 The effects of nitroxide radicals on oxidative DNA damage. Free Radic Biol Med 28, 1257–1265.Google Scholar
  7. De Bono D, Yang WD, Symons MCR. 1994 The effect of myoglobin on the stability of the hydroxyl-radical adducts of 5,5-dimethyl-1-pyrolline-N-oxide (DMPO), 3,3,5,5-tetramethyl-1-pyrolline-N-oxide (TMPO) and 1-alpha-phenyl-tert-butyl nitrone (PBN) in the presence of hydrogen peroxide. Free Radical Res 20, 327–332.Google Scholar
  8. Deffner U, Schimmack W. 1976 Radiation effects on aqueous solutions of the nitroxyl free radical TMPN (2,2,6,6-tetramethyl-4-piperidinol-N-oxyl). Int J Radiat Biol Relat Stud Phys Chem Med 29, 71–75.Google Scholar
  9. Floyd RA, Nagy I. 1984 Formation of long-lived hydroxyl free radical adducts of proline and hydroxyproline in a Fenton reaction. Biochim Biophys Acta 790, 94–97.Google Scholar
  10. Franzini E, Sellak H, Hakim J, Pasquier C. 1994 Comparative sugar degradation by (OH). produced by the iron-driven Fenton reaction and gamma radiolysis. Arch Biochem Biophys 309, 261–265.Google Scholar
  11. Glebska J, Gwozdzinski K. 1998 Oxygen-dependent reduction of nitroxides by ascorbic acid and glutathione. An EPR study. Curr Topics Biophys 22(Suppl B), 75–82.Google Scholar
  12. Gutteridge JM. 1984 Reactivity of hydroxyl and hydroxyl-like radicals discriminated by release of thiobarbituric acid-reactive material from deoxy sugars, nucleosides and benzoate. Biochem J 224, 761–767.Google Scholar
  13. Halliwell B, Gutteridge JM, Aruoma OI. 1987 The deoxyribose method: a simple ‘test-tube’ assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem 165, 215–219.Google Scholar
  14. Knight JA, Pieper RK, McClellan L. 1988 Specificity of the thiobarbituric acid reaction: its use in studies of lipid peroxidation. Clin Chem 34, 2433–2438.Google Scholar
  15. Koppenol WH, Butler J. 1985 Energetics of interconversion reactions of oxyradicals. Adv Free Radical BiolMed 1, 91–131.Google Scholar
  16. Koppenol WH, Liebman JF. 1984 The oxidizing nature of the hydroxyl radical. A comparison with the ferryl ion (FeO2+). J Phys Chem 88, 99–101.Google Scholar
  17. Krishna MC, DeGraff W, Hankovszky OH et al. 1998 Studies of structure-activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage. J Med Chem 41, 3477–3492.Google Scholar
  18. Krishna MC, Samuni A. 1994 Nitroxides as antioxidants. Methods Enzymol 234, 580–589.Google Scholar
  19. Krishna MC, Samuni A, Taira J, Goldstein S, Mitchell JB, Russo A. 1996 Stimulation by nitroxides of catalase-like activity of heme proteins. Kinetics and mechanism. J Biol Chem 271, 26018–26025.Google Scholar
  20. Lloyd RV, Hanna PM, Mason RP. 1997 The origin of the hydroxyl radical oxygen in the Fenton reaction. Free Radic Biol Med 22, 885–888.Google Scholar
  21. Malatesta V, Ingold KU. 1973 Kinetic applications of electron paramagnetic resonance spectroscopy. XI. Aminium radicals. J Am Chem Soc 95, 6400–6404.Google Scholar
  22. Mathew AE, Massoth RJ, Zimbrick JD. 1980 Radiation-induced oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine to paramagnetic nitroxide free radicals. Int J Radiat Biol Relat Stud Phys Chem Med 37, 315–319.Google Scholar
  23. Metodiewa D, Kochman A, Skolimowski J, Gebicka L, Koska C. 1999 Metexyl (4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl) as an oxygen radicals scavenger and apoptosis inducer in vivo. Anticancer Res 19, 5259–5264.Google Scholar
  24. Metodiewa D, Skolimowski J, Kochman A, Gwozdzinski K, Glebska J. 1998 Tempicol-2 (4-hydroxy-4-(2-picolyl)-2,2,6,6-tetramethylpiperidine-1-oxyl), a stable free radical, is a novel member of nitroxide class of antioxidants and anticancer agents. Anticancer Res 18, 369–377.Google Scholar
  25. Miller DM, Buettner GR, Aust SD. 1990 Transition metals as catalysts of ‘autoxidation’ reactions. Free Radic Biol Med 8, 95–108.Google Scholar
  26. Mohsen M, Pinson A, Zhang R, Samuni A. 1995 Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide? Mol Cell Biochem 145, 103–110.Google Scholar
  27. Morris S, Sosnovsky G, Hui B, Huber CO, Rao NU, Swartz HM. 1991 Chemical and electrochemical reduction rates of cyclic nitroxides (nitroxyls). J Pharm Sci 80, 149–152.Google Scholar
  28. Nilsson UA, Olsson LI, Carlin G, Bylund-Fellenius AC. 1989 Inhibition of lipid peroxidation by spin labels. Relationships between structure and function. J Biol Chem 264, 11131–11135.Google Scholar
  29. Offer T, Russo A, Samuni A. 2000 The pro-oxidative activity of SOD and nitroxide SOD mimics. FASEB J 14, 1215–1223.Google Scholar
  30. Rozantsev EG. 1970 Free Nitroxyl Radicals, New York: Plenum Publishers.Google Scholar
  31. Samuni A, Winkelsberg D, Pinson A, Hahn SM, Mitchell JB, Russo A. 1991 Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage. J Clin Invest 87, 1526–1530.Google Scholar
  32. Samuni AM, Barenholz Y, Crommelin DJ, Zuidam NJ. 1997 Gamma-irradiation damage to liposomes differing in composition and their protection by nitroxides. Free Radic Biol Med 23, 972–979.Google Scholar
  33. Shen X, Tian J, Li J, Li X, Chen Y. 1992 Formation of the excited ferryl species following Fenton reaction. Free Radic Biol Med 13, 585–592.Google Scholar
  34. Skolimowski J. 1999 Synthesis, Spectroscopic Investigations and Applications of Nitroxide Radicals and Their Derivatives, Lodz: University of Lodz Press.Google Scholar
  35. Udassin R, Haskel Y, Samuni A. 1998 Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small intestine. Gut 42, 623–627.Google Scholar
  36. Winterbourn CC. 1991 Factors that influence the deoxyribose oxidation assay for Fenton reaction products. Free Radic Biol Med 11, 353–360.Google Scholar
  37. Yeo HC, Helbock HJ, Chyu DW, Ames BN. 1994 Assay of malondialdehyde in biological fluids by gas chromatography-mass spectrometry. Anal Biochem 220, 391–396.Google Scholar
  38. Zhang R, Goldstein S, Samuni A. 1999 Kinetics of superoxideinduced exchange among nitroxide antioxidants and their oxidized and reduced forms. Free Radic Biol Med 26, 1245–1252.Google Scholar
  39. Zhang R, Pinson A, Samuni A. 1998 Both hydroxylamine and nitroxide protect cardiomyocytes from oxidative stress. Free Radic Biol Med 24, 66–75.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Jolanta Glebska
    • 1
  • Lukasz Pulaski
    • 1
  • Krzysztof Gwozdzinski
    • 1
  • Janusz Skolimowski
    • 2
  1. 1.Department of Molecular BiophysicsUniversity of LodzLodzPoland
  2. 2.Department of Organic ChemistryUniversity of LodzLodzPoland

Personalised recommendations