Noninvasive evaluation of in vivo free radical reactions catalyzed by iron using in vivo ESR spectroscopy.
The noninvasive, real time technique of in vivo electron spin resonance (ESR) spectroscopy was used to evaluate free radical reactions catalyzed by iron in living mice. The spectra and signal decay of a nitroxyl probe, carbamoyl-PROXYL, were observed in the upper abdomen of mice. The signal decay was significantly enhanced in mice subcutaneously loaded with ferric citrate (0.2 micromol/g body wt) and the enhancement was suppressed by pre-treatment with either desferrioxamine (DF) or the chain breaking antioxidant Trolox, but only slightly suppressed by the hydroxyl radical scavenger DMSO. To determine the catalytic form of iron, DF was administered at different times with respect to iron loading: before, simultaneously, and after 20 and 50 min. The effect of DF on signal decay, liver iron content, iron excretion, and lipid peroxidation (TBARs) depended on the time of the treatment. There was a good correlation between the signal decay, iron content, and lipid peroxidation, indicating that "chelatable iron" contributed to the enhanced signal decay. The nitroxyl probe also exhibited in vivo antioxidant activity, implying that the process responsible for the signal decay of the nitroxyl probe is involved in free radical oxidative stress reactions catalyzed by iron.
Phumala
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Department of Biophysics, Faculty of Pharmaceutical Science, Kyushu University, Fukuoka, Japan.
Ide
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Utsumi
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005069:Evaluation Studies as Topic; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D011759:Pyrrolidines; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D002614:Chelating Agents; D002839:Chromans; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; D007501:Iron; D003676:Deferoxamine; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004121:Dimethyl Sulfoxide