title: The nitroxide Tempo inhibits hydroxyl radical production from the Fenton-like reaction of iron(II)-citrate with hydrogen peroxide.
abstract: In vivo physiological ligand citrate can bind iron(II) ions to form the iron(II)-citrate complex. Inhibition of hydroxyl radical (OH) production from the Fenton-like reaction of iron(II)-citrate with H2O2is biologically important, as this reaction may account for one of the mechanisms of the labile iron pool in vivo to induce oxidative stress and pathological conditions. Nitroxides have promising potentials as therapeutic antioxidants. However, there are controversial findings indicating that they not only act as antioxidants but also as pro-oxidants when engaged in Fenton reactions. Although the underlying mechanisms are proposed to be the inhibition or enhancement of the OH production by nitroxides, the proposed elucidations are only based on assessing biological damages and not demonstrated directly by measuring the OH production in the presence of nitroxides. In this study, therefore, we employed EPR and fluorescence spectroscopies to show direct evidence that nitroxide 2,2,6,6-tetramethyl-piperidine-1-oxyl (Tempo) inhibited OH production from the Fenton-like reaction of iron(II)-citrate with H2O2by up to 90%. We also demonstrated spectrophotometrically, for the first time, that this inhibition was due to oxidation of the iron(II)-citrate by Tempo with a stoichiometry of Tempo:Iron(III)-citrate = 1.1:1.0. A scheme was proposed to illustrate the roles of nitroxides engaged in Fenton/Fenton-like reactions.
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Fengqiang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China. Electronic address: zzhao@ccmu.edu.cn.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D002951:Citrates / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005296:Ferrous Compounds / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D010084:Oxidation-Reduction; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002951:Citrates; D003497:Cyclic N-Oxides; D005296:Ferrous Compounds; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; C003959:TEMPO
keywords: EPR; Fenton-like reaction; Fluorescence; Iron(II)-citrate complex; Nitroxide Tempo; Reactive oxygen species