Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10739360 | Free Radical Biology and Medicine | 2005 | 10 Pages |
Abstract
α-Lipoic acid (LA) and dihydrolipoic acid (DHLA) may have a role as antioxidants against nitric oxide-derived oxidants. We previously reported that peroxynitrite reacts with LA and DHLA with second-order rate constants of 1400 and 500 Mâ1 sâ1, respectively, but indicated that these direct reactions are not fast enough to protect against peroxynitrite-mediated damage in vivo. Moreover, the mechanism of the reaction of peroxynitrite with LA has been recently challenged (J. Biol. Chem.279:9693-9697; 2004). Pulse radiolysis studies indicate that LA and DHLA react with peroxynitrite-derived nitrogen dioxide (NO2) (k2 = 1.3 à 106 and 2.9 à 107 Mâ1 sâ1, respectively) and carbonate radicals (CO3â) (k2 = 1.6 à 109 and 1.7 à 108 Mâ1 sâ1, respectively). Carbonate radical-mediated oxidation of LA led to the formation of the potent one-electron oxidant LA radical cation. LA inhibited peroxynitrite-mediated nitration of tyrosine and of a hydrophobic tyrosine analog, N-t-BOC L-tyrosine tert-butyl ester (BTBE), incorporated into liposomes but enhanced tyrosine dimerization. Moreover, while LA competitively inhibited the direct oxidation of glutathione by peroxynitrite, it was poorly effective against the radical-mediated thiol oxidation. The mechanisms of reaction defined herein allow to rationalize the biochemistry of peroxynitrite based on direct and free radical-mediated processes and contribute to the understanding of the antioxidant actions of LA and DHLA.
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Authors
Madia Trujillo, Lisa Folkes, Silvina Bartesaghi, Balaraman Kalyanaraman, Peter Wardman, Rafael Radi,