title: 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.
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-tetra-methylpiperidine-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.
authors.affiliation: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Japan, Midorigaoka, Ikeda, Osaka 563-8577, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shimakawa
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
mesh_terms: D000388:Air; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D015687:Cell Hypoxia; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D005609:Free Radicals / Q000494:pharmacology*; D019811:Hydroxylamine / Q000494:pharmacology; D048289:Imidazolidines; D008041:Linoleic Acids / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D009584:Nitrogen; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen; D011312:Pressure; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001559:Benzhydryl Compounds; D003510:Cyclohexanes; D005609:Free Radicals; D048289:Imidazolidines; D008041:Linoleic Acids; D009589:Nitrogen Oxides; D013141:Spiro Compounds; C481122:cyclohexane-1-spiro-2'-(4'-oxyimidazolidine-1'-oxyl)-5'-spiro-1''-cyclohexane; C005575:methyl linoleate; D019811:Hydroxylamine; C039900:nitroxyl; D009584:Nitrogen; D001205:Ascorbic Acid; D010100:Oxygen; C020338:galvinoxyl