Protection against peroxynitrite‐dependent tyrosine nitration and α₁‐antiproteinase inactivation by oxidized and reduced lipoic acid

Abstract

Peroxynitrite, formed by combination of superoxide radical with nitric oxide, is a reactive tissue-damaging species apparently involved in the pathology of several human diseases. Peroxynitrite nitrates tyrosine residues and inactivates vq-antiproteinase. We show that both lipoic acid and dihydrolipoic acid efficiently protect against damage by peroxynitrite. By contrast, other disulphides tested did not. The biological antioxidant effects of lipoateldihydrolipoate may involve scavenging of reactive nitrogen species as well as reactive oxygen species.

Lipoic Acid Protects Efficiently Only against a Specific Form of Peroxynitrite-induced Damage

“…The IC 50 value of LA is six times lower than the initial concentration of ONOOH with tyrosine as a detector (IC 50 ϭ 24 M; initial concentration of ONOOH ϭ 150 M) and Ͼ10 times lower than that of GST-P1-1 (IC 50 ϭ 0.9 M; initial concentration of ONOOH ϭ 10 M). A similar difference was reported in the study of Whiteman et al (2); the IC 50 value of LA for the inhibition of tyrosine nitration was 10 times as low as the initial concentration of ONOOH. Theoretically, in a standard competition assay the minimal IC 50 of the antioxidant is equal to half of the initial concentration of oxidant, i.e.…”

“…This makes it unlikely that LA reacts with several ONOOH molecules. The second explanation of Whiteman et al (2), i.e. that LA can combine with the reactive intermediates of ONOOH, seems more plausible.…”

“…that LA can combine with the reactive intermediates of ONOOH, seems more plausible. Whiteman et al (2) stated that these intermediate products of ONOOH could be NO 2 . and NO 2 ϩ .…”

“…Some sulfur-containing compounds are efficient antioxidants and can protect against damage induced by peroxynitrite (ONOOH) 1 (1)(2)(3)(4)(5) and hypochlorous acid (HOCl) (6,7). ONOOH and HOCl are highly effective antibacterial agents formed by neutrophils in innate immunity (8).…”

“…low density lipoprotein (LDL) oxidation or DNA, RNA, and protein damage (9 -13). ONOOH is known to mediate both oneand two-electron oxidation reactions, whereas HOCl predominantly gives two-electron oxidation (14,15) It has been found that lipoic acid (LA) is a very potent protector against ONOOH-mediated damage (1)(2)(3)(4). In contrast, preliminary studies in our laboratory indicated that LA is a very poor protector against ONOOH-mediated oxidation of dihydrorhodamine-123 (DHR-123).…”