Lipids

, Volume 38, Issue 3, pp 225–231 | Cite as

Antioxidant action of a lipophilic nitroxyl radical, cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-oxyl)-5′-spiro-1″-cyclohexane, against lipid peroxidation under hypoxic conditions

Articles

Abstract

Nitroxyl radicals are known to act as radical scavenging antioxidants. In the present study, a lipophilic nitroxyl radical, cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-oxyl)-5′-spiro-1″-cyclohexane (nitroxyl radical I) was synthesized and its antioxidant capacity was assessed in comparison with a hydrophilic nitroxyl radical, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol). Both nitroxyl radical I and Tempol inhibited methyl linoleate oxidation induced by free radicals, and the efficacy increased with decreasing partial pressure of oxygen, the effect being more pronounced for nitroxyl radical I than Tempol. Their hydroxylamines inhibited lipid peroxidation more effectively than their corresponding parent nitroxyl radicals. In liposomal membranes, a synergistic effect was observed in the combination of nitroxyl radical I with ascorbic acid, whereas only an additive effect was observed between Tempol and ascorbic acid. The present study suggests that nitroxyl radical I and its hydroxylamine may act as potent antioxidants, especially in combination with ascorbic acid under hypoxic conditions.

Abbreviations

14∶0 PC

l-α-phosphatidylcholine dimyristoyl

AAPH

2,2′-azobis(2-amidinopropane)dihydrochloride

AMVN

2,2′-azobis(2,4-dimethylvaleronitrile)

I-H

cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-hydroxyl)-5′-spiro-1″-cyclohexane

MeLH

methyl linoleate; nitroxyl radical I, cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-oxyl)-5′-spiro-1″-cyclohexane

PLPC

l-α-phosphatidylcholine,β-linoleoxyl-γ-palmitoyl

Tempol

4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl

Tempol-H

4-hydroxy-2,2,6,6-tetramethylpiperidine-N-hydroxyl

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References

  1. 1.
    Halliwell, B., and Gutteridge, J.M.C. (1985) Free Radicals in Biology and Medicine, Clarendon Press, Oxford.Google Scholar
  2. 2.
    Brownlie, I.T., and Ingold, K.U. (1967) The Inhibited Autoxidation of Styrene. Part VII. Inhibition by Nitroxides and Hydroxylamines, Can. J. Chem. 45, 2427–2432.CrossRefGoogle Scholar
  3. 3.
    Zeltcer, G., Berenshtein, E., Samuni, A., and Chevion, M. (1997) Nitroxide Radicals Prevent Metal-Aggravated Reperfusion Injury in Isolated Rat Heart, Free Radic. Res. 27, 627–636.PubMedGoogle Scholar
  4. 4.
    Wink, D.A., Feelisch, M., Fukuto, J., Chistodoulou, D., Jour-d'heuil, D., Grisham, M.B., Vodovotz, Y., Cook, J.A., Krishna, M., DeGraff, W.G., et al. (1998) The Cytotoxicity of Nitroxyl: Possible Implications for the Pathophysiological Role of NO, Arch. Biochem. Biophys. 351, 66–74.PubMedCrossRefGoogle Scholar
  5. 5.
    McDonald, M.C., Zacharowski, K., Bowes, J., Cuzzocrea, S., and Thiemermann, C. (1999) Tempol Reduces Infarct Size in Rodent Models of Regional Myocardial Ischemia and Reperfusion, Free Radic. Biol. Med. 27, 493–503.PubMedCrossRefGoogle Scholar
  6. 6.
    Rak, R., Chao, D.L., Pluta, R.M., Mitchell, J.B., Oldfield, E.H., and Watson, J.C. (2000) Neutroprotection by the Stable Nitroxide Tempol During Reperfusion in a Rat Model of Transient Focal Ischemia, J. Neurosurg. 92, 646–651.PubMedCrossRefGoogle Scholar
  7. 7.
    Noguchi, N., Damiani, E., Greci, L., and Niki, E. (1997) Action of Quinolinic and Indolinonic Aminoxyls as Radical-Scavenging Antioxidants, Chem. Phys. Lipids 99, 11–19.CrossRefGoogle Scholar
  8. 8.
    Carloni, P., Damiani, E., Scattolini, M., Stipa, P., and Greci, L. (2000) Reactivity of 2,2-Diphenyl-1,2-dihydro-4-ethoxyquinolin-1-yloxyl Towards Oxygen- and Carbon-Centered Radicals, J. Chem. Soc. Perkin Trans. 2, 447–451.Google Scholar
  9. 9.
    Niki, E., and Noguchi, N. (2000) Evaluation of Antioxidant Capacity. What Capacity Is Being Measured by Which Method? IUBMB Life 50, 323–329.PubMedCrossRefGoogle Scholar
  10. 10.
    Murayama, K., Morimura, S., and Yoshioka, T. (1969) Studies on Stable Free Radicals. II. Reactivity of Stable Nitroxide Radicals and NMR Spectra of Reaction Products, Bull. Chem. Soc. Jpn. 42, 1640–1643.CrossRefGoogle Scholar
  11. 11.
    Noguchi, N., Okimoto, Y., Tsuchiya, J., Cynshi, O., Kodama, T., and Niki, E. (1997) Inhibition of Oxidation of Low-Density Lipoprotein by a Novel Antioxidant, BO-653, Prepared by Theoretical Design, Arch. Biochem. Biophys. 347, 141–147.PubMedCrossRefGoogle Scholar
  12. 12.
    Shi, H., Noguchi, N., and Niki, E. (2001) Galvinoxyl Method for Standardizing Electron and Proton Donation Activity, Methods Enzymol. 335, 157–166.PubMedGoogle Scholar
  13. 13.
    Noguchi, N., and Niki, E. (1998) Dynamics of Vitamin E Action Against LDL Oxidation, Free Radic. Res. 28, 561–572.PubMedCrossRefGoogle Scholar
  14. 14.
    Kamal-Eldin, A., and Appelqvist, L.A. (1996) The Chemistry and Antioxidant Properties of Tocopherols and Tocotrienols, Lipids 31, 671–701.PubMedCrossRefGoogle Scholar
  15. 15.
    Yamamoto, Y., Niki, e., and Kamiya, Y. (1982) Oxidation of Lipids. I. Quantitative Determination of the Oxidation of Methyl Linoleate and Methyl Linolenate, Bull. Chem. Soc. Jpn. 55, 1548–1550.CrossRefGoogle Scholar
  16. 16.
    Porter, N.A., Caldwell, S.E., and Mills, K.A. (1995) Mechanisms of Free Radical Oxidation of Unsaturated Lipids, Lipids 30, 277–290.PubMedGoogle Scholar
  17. 17.
    Takahashi, M., Tsuchiya, J., Niki, E., and Urano, S. (1988) Action of Vitamin E as Antioxidant in Phospholipid Liposomal Membranes as Studied by Spin Label Technique. J. Nutr. Sci. Vitaminol. 34, 25–34.PubMedGoogle Scholar
  18. 18.
    Gotoh, N., Noguchi, N., Tsuchiya, J., Morita, K., Sakai, H., Shimasaki, H., and Niki, E. (1996) Inhibition of Oxidation of Low Density Lipoprotein by Vitamin E and Related Compounds, Free Radic. Res. 24, 123–134.PubMedGoogle Scholar

Copyright information

© AOCS Press 2003

Authors and Affiliations

  • Shuichi Shimakawa
    • 1
  • Yasukazu Yoshida
    • 1
  • Etsuo Niki
    • 1
  1. 1.AISTHuman Stress Signal Research CenterOsakaJapan

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