Lacidipine, a potential peroxynitrite scavenger: investigation of activity by liquid chromatography and mass spectrometry.
Inflamed tissues are often characterised by the production of *NO and O(2)(-) radicals, which are known to react at an extremely fast rate to produce peroxynitrite (ONOO(-)). This highly oxidising entity reacts with protein-bound tyrosine to give 3-nitrotyrosine, which is considered a biochemical marker of peroxynitrite-induced damage. Lacidipine is a calcium antagonist indicated for the treatment of mild to moderate hypertension. In the present work, electrospray mass spectrometry with and without liquid chromatography was used to evaluate the capability of lacidipine and two other related molecules as ONOO(-) scavengers. This capability is compared with that associated with a number of commercial polyphenols described in the literature as efficient scavengers of this cytotoxic agent. The use of mass spectrometry provided rapid quantitative assessment of both the nitration and its reduction, and showed that lacidipine possesses a reasonable capability for reducing in vitro nitration of superoxide dismutase.
Garzotti
Marco
M
Computational, Analytical and Structural Sciences, GlaxoSmithKline SpA, Medicines Research Centre, Verona, Italy. mag92802@gsk.com
D000818:Animals; D002417:Cattle; D002853:Chromatography, Liquid / Q000379:methods; D004095:Dihydropyridines / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D030421:Peroxynitrous Acid / Q000378:metabolism*; D013482:Superoxide Dismutase
D004095:Dihydropyridines; D030421:Peroxynitrous Acid; C060285:lacidipine; D013482:Superoxide Dismutase