Nitric oxide reaction with lipid peroxyl radicals spares α-tocopherol during lipid peroxidation -: Greater oxidant protection from the pair nitric oxide/α-tocopherol than α-tocopherol/ascorbate

The reactions of nitric oxide ((NO)-N-.) and alpha-tocopherol (alpha-TH) during membrane lipid oxidation were examined and compared with the pair alpha-TH/ascorbate. Nitric oxide serves as a more potent inhibitor of lipid peroxidation propagation reactions than alpha-TH and protects alpha-TH from oxidation, Mass spectrometry, oxygen and (NO)-N-. consumption, conjugated diene analyses, and alpha-TH fluorescence determinations all demonstrated that (NO)-N-. preferentially reacts with lipid radical species, with alpha-TH consumption not occurring until (NO)-N-. concentrations fell below a critical level. In addition, alpha-TH and (NO)-N-. cooperatively inhibit lipid peroxidation, exhibiting greater antioxidant capacity than the pair alpha-TH/ascorbate. Pulse radiolysis analysis showed no direct reaction between (NO)-N-. and alpha-tocopheroxyl radical (alpha-T-.), inferring that peroxyl radical termination reactions are the principal lipid-protective mechanism mediated by (NO)-N-.. These observations support the concept that (NO)-N-. is a potent chain breaking antioxidant toward peroxidizing lipids, due to facile radical-radical termination reactions with lipid radical species, thus preventing alpha-TH loss. The reduction of alpha-T-. by ascorbate was a comparatively less efficient mechanism for preserving alpha-TH than (NO)-N-.-mediated termination of peroxyl radicals, due to slower reaction kinetics and limited transfer of reducing equivalents from the aqueous phase. Thus, the high lipid/water partition coefficient of (NO)-N-., its capacity to diffuse and concentrate in lipophilic milieu, and a potent reactivity toward lipid radical species reveal how (NO)-N-. can play a critical role in regulating membrane and lipoprotein lipid oxidation reactions.