Peroxynitrite radical

In order to produce the peroxynitrite radicals that damage DNA, the thick-layer biosensor has to be first incubated in the solution of DETA/ NO and then conditioned at —0.60 V such that O2 reacts with NO preconcentrated into the thick DNA film. On the contrary, the production of peroxynitrite at the multi-layer dsDNA biosensor is carried out in a single step. 

For higher DETA/NO concentrations, the DP voltammogram showed two large oxidation peaks for dGuo and dAdo plus a third peak at a lower potential, Epa — + 0.77 V (Fig. 20.10). This peak is a consequence of the interaction between peroxynitrite radicals and DNA, corresponding to guanine (Gua) oxidation. 

Two radicals that play predominant roles as initiators of lipid peroxidation are the hydroxyl radical (OH ) and the peroxynitrite radical (OONO ). The superoxide anion radical (0 ), which is generated during the electron transport process in mitochondria, is involved in the generation of both OH and OONO. Superoxide dis-mutase (MnSOD and Cu/ZnSOD) converts O2 to hydrogen peroxide (H2O2), which is then converted to OH via the... 

S,2LS-dimethyl derivative of M40403 (M40401) possesses the highest catalytic rate for 02 dismutation at pH=7.4 of any known synthetic mimetic, which exceeds that of native mitochondrial MnSOD 13h). Some of these complexes are the first SOD mimetics which entered chnical trials 13). It has been claimed that these compounds are highly selective, that is, they do not react with hydrogen peroxide or with other biological relevant oxidants such as NO or peroxynitrite radicals 13) (Scheme 1). 

Enhanced production of vasoconstrictor factors via eicosanoid and/or free radical-related mechanisms has been observed in several cardiovascular disease states. In addition to the well-established role of free radicals in promoting the oxidation of low density lipoprotein cholesterol (LDL-C), changes in free radical status may modify endogenous eicosanoid profiles and/or produce nonenzymatic lipid peroxidation products of the arachidonic acid (AA) cascade such as lipid hydroperoxides and isoprostanes, which have been shown to possess potent vasoactive properties (3). Furthermore, an excess of free radicals may interact with the vascular endothelial cell nitric oxide (NO) to produce highly reactive peroxynitrite radicals, resulting in tissue damage and vasoconstriction (4—6) (Fig. 2). 

A few examples of ROS and free radicals include the superoxide anion, hydrogen peroxide, the hydroxyl radical, peroxynitrite radical. 

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A. and Freeman, B.A. (1990). Apparent hydroxyl radical production by peroxynitrite implication for endothelial injury from nitric oxide and superoxide. Proc. Natl Acad. Sci. USA 87, 1620-1624. 

Peroxynitrite, a non-radical product, is formed by the reaction of NO and CV-and is highly toxic to cells. 

At physiological pH, ONOO- protonates to peroxynitrous acid (ONOOH) which disappears within a few seconds, the end product being largely nitrate. The chemistry of peroxynitrite/peroxynitrous acid is extremely complex, although addition of ONOO to cells and tissues leads to oxidation and nitration of proteins, DNA and lipids with a reactivity that is comparable to that of hydroxyl radicals. 

Protein tyrosine residues constitute key targets for peroxynitrite-mediated nitrations. Attack of various free radicals (ONOO-, N02 ) upon tyrosine generates 3-nitrotyrosine, which can be measured immunologically or by GC/MS or HPLC techniques. The detection of 3-nitrotyrosine was considered a biomarker of peroxynitrite action in vivo. Similarly, attack of HOC1 and HOBr on tyrosine generates chlorotyro-sine and bromotyrosine, respectively, both of which are measured most accurately by GC-MS. 

The 3-morpholinosydnonimine system generates superoxide radicals and nitrogen monoxide, forming peroxynitrite, which releases ethane from KMB (a-keto-y-methiolbutyric acid). This method was used by Lavelli and others (1999) to investigate the radical-scavenging activity of fresh and air-dried tomatoes. 

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