Metabolic stability of superoxide adducts derived from newly developed cyclic nitrone spin traps. Free Radic Biol Med 2014 Feb;67:150-8
Date
10/29/2013Pubmed ID
24161442DOI
10.1016/j.freeradbiomed.2013.10.812Scopus ID
2-s2.0-84888126364 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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.
Author List
Bézière N, Hardy M, Poulhès F, Karoui H, Tordo P, Ouari O, Frapart YM, Rockenbauer A, Boucher JL, Mansuy D, Peyrot FAuthor
Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytosol
Electron Spin Resonance Spectroscopy
Hepatocytes
Hydrogen Peroxide
Hydroxyl Radical
Kinetics
Liver
Male
Microsomes, Liver
Nitrogen Oxides
Peroxynitrous Acid
Rats
Rats, Sprague-Dawley
Spin Labels
Spin Trapping
Stereoisomerism
Superoxides