Metabolic stability of superoxide adducts derived from newly developed cyclic nitrone spin traps

Bézière, Nicolas and Hardy, Micael and Poulhès, Florent and Karoui, Hakim and Tordo, Paul and Rockenbauer, Antal (2014) Metabolic stability of superoxide adducts derived from newly developed cyclic nitrone spin traps. FREE RADICAL BIOLOGY AND MEDICINE, 67. pp. 150-158. ISSN 0891-5849


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Reactive oxygen species are by-products of aerobic metabolism involved in the onset and evolution of various pathological conditions. Among them, the superoxide radical is of special interest as the origin of several damaging species such as H2O2, hydroxyl radical, or peroxynitrite (ONOO-). Spin trapping coupled with ESR is a method of choice to characterize these species in chemical and biological systems and the metabolic stability of the spin adducts derived from reaction of superoxide and hydroxyl radicals with nitrones is the main limit to the in vivo application of the method. Recently, new cyclic nitrones bearing a triphenylphosphonium or permethylated β-cyclodextrin moiety have been synthesized and their spin adducts demonstrated increased stability in buffer. In this article, we studied the stability of the superoxide adducts of four new cyclic nitrones in the presence of liver subcellular fractions and biologically relevant reductants using an original setup combining a stopped-flow device and an ESR spectrometer. The kinetics of disappearance of the spin adducts were analyzed using an appropriate simulation program. Our results highlight the interest of the new spin trapping agents CD-DEPMPO and CD-DIPPMPO for specific detection of superoxide with high stability of the superoxide adducts in the presence of liver microsomes. © 2013 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: synthesis; SIMULATION; signal noise ratio; RAT; priority journal; nonhuman; molecular stability; Male; LIVER; electron spin resonance; controlled study; Cell Fractionation; ARTICLE; animal experiment; unclassified drug; reactive oxygen metabolite; nitrone derivative; cyclic nitrone derivative; beta cyclodextrin; ascorbic acid; 5 diethoxyphosphoryl 5 methyl 1 pyrroline 1 oxide; SUPEROXIDE; Spin Trapping; Spin adduct stability; Hydroxyl Radical; Free Radicals; ESR spectroscopy; EPR spectroscopy; Cyclic nitrones
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 03 Dec 2014 14:24
Last Modified: 03 Dec 2014 14:24

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