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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

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Lipids

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.

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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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Authors and Affiliations

  1. AIST, Human Stress Signal Research Center, 1-8-31 Midorigaoka, Ikeda, 563-8577, Osaka, Japan

    Shuichi Shimakawa, Yasukazu Yoshida & Etsuo Niki

Authors
  1. Shuichi Shimakawa
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  2. Yasukazu Yoshida
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  3. Etsuo Niki
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Correspondence to Yasukazu Yoshida.

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Shimakawa, S., Yoshida, Y. & Niki, E. 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. Lipids 38, 225–231 (2003). https://doi.org/10.1007/s11745-003-1055-3

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  • DOI: https://doi.org/10.1007/s11745-003-1055-3

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