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Inhibition of lipid peroxidation by nitrates and nitrites

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în volumul unei conferinţe

Autori: Nicolescu, A.C., Toader, V., Zavorin, S.I., Artz, J.D., Smith, S.V., Reynolds, J.N., Thatcher, G.R

Editorial: Proc. Soc. Neurosci., 31, p.8, 2001.


Evidence exists for both the cytoprotective and cytotoxic effects of the endogenous chemical messenger, nitric oxide (NO). Oxidative damage to lipid constituents of biological membranes is implicated in many disease states, with growing evidence for: a causative role for Fe in lipid peroxidation; and links between disruption of Fe homeostasis, Fe-induced oxidative stress, and neurodegeneration. Peroxynitrite may induce peroxidation, but NO itself may be cytoprotective as an apparent antioxidant. Exogenous sources of NO, the NO-donor NONOates, and the clinically important nitrates and nitrites are of interest as potential inhibitors of lipid peroxidation, but nitrates and nitrites are of special interest, since the antioxidant action of endogenous NO has been proposed to result in formation of lipid nitrites and nitrates. The effects of NONOates, nitrates and nitrites on lipid peroxidation in synaptosomes and liposomes, induced by ferrous ion and other initiators, was studied by determining TBARS, peroxide, and other methods, benchmarked against vitamin E and lipoic acid related pro- and anti-oxidants. Comparison of IC50 for lipid peroxidation with measured rates of NO release gave a linear correlation for NONOate inhibition of lipid peroxidation. Classical nitrates, e.g. nitroglycerin, had no activity, whereas novel nitrates inhibited lipid peroxidation in the presence of prooxidant thiols. Nitrites showed potent antioxidant activity in a concentration-dependent and structure-correlated manner. The results support the novel hypothesis of a role for lipid nitrites and nitrates as endogenous membrane antioxidants.

Cuvinte cheie: lipid peroxidation, antioxidants, nitric oxid, organic nitrates, organic nitrites