5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: a new efficient phosphorylated nitrone for the in vitro and in vivo spin trapping of oxygen-centered radicals

C Frejaville, H Karoui, B Tuccio… - Journal of medicinal …, 1995 - ACS Publications
C Frejaville, H Karoui, B Tuccio, FL Moigne, M Culcasi, S Pietri, R Lauricella, P Tordo
Journal of medicinal chemistry, 1995ACS Publications
Enormous efforts are still being devoted to addressing the role played by partially reduced
oxygen species such as superoxide 02*" and hydroxyl HO" radicals in medi-ating a variety of
pathologicalconditions, including toxicity due to several chemicals and ionizing radiation,
carcinogenesis, inflammation, and degenerative diseases such as immunodeficiencies,
aging, and atherosclerosis. 2 In particular, these oxygen-derived free radicals have been
implicated in theso-called ischemia/reperfusion injury, 3 the cytotoxicity occurring when …
Enormous efforts are still being devoted to addressing the role played by partially reduced oxygen species such as superoxide 02*" and hydroxyl HO" radicals in medi-ating a variety of pathologicalconditions, including toxicity due to several chemicals and ionizing radiation, carcinogenesis, inflammation, and degenerative diseases such as immunodeficiencies, aging, and atherosclerosis. 2 In particular, these oxygen-derived free radicals have been implicated in theso-called ischemia/reperfusion injury, 3 the cytotoxicity occurring when tissues sub-jected to partial or total oxygen deprivation are reoxygenated.
Of themethods available for assessing free radical formation in biological systems, electron spin resonance (ESR) spin trapping appears one of the mostappropriate and has been applied to investigate myocardial reperfusion injury in animal models. 4 Nitrones have emerged as the most popular spin traps for biological applica-tions, 5 and out of several nitrone spin traps, the cyclic 5, 5-dimethyl-l-pyrroline IV-oxide (DMPO) has received the most attention, since it yields distinct and charac-teristic spin adducts with O2'-and HO* radicals. 5, 6 Such results are worth considering on their own merits and have stimulated our research; however, the use of DMPO as a probe for oxyradical generation in biological milieu is not without its limitations. 5-7 Reaction of DMPO with superoxide is rather slow, having a second-order rate constant ranging from 10 M-1 s-1 at pH 7.8® to 1.2 M-1 s-1 at pH 7.4. 8 9
ACS Publications