Oxides and superoxides

P.J. Goddard, and R.M. Lambert, Basic studies of the oxygen surface chemistry of silver Oxygen, dioxygen, oxide and superoxide on rubidium-dosedAg(l 1 ),Surf. Sci. 107,519-532(1981). 

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). 

Nitric oxide may also be an antioxidant by virtue of the feet that it can directly inhibit NADPH oxidase and thus prevent superoxide production (Clancy etaJ., 1992). This inhibition was reported to be independent of the reaction between nitric oxide and superoxide, which might be expected to be pro-oxidant (see Section 2.2.3). 

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

The material is presented in 17 chapters, covering topics such as trends in ion selective electrodes, advances in electrochemical immunosensors, modem glucose biosensors for diabetes management, biosensors based on nanomaterials (e.g. nanotubes or nanocrystals), biosensors for nitric oxide and superoxide, or biosensors for pesticides. 

Peroxynitrite (ONOO-) is a cytotoxic reactive species that is formed by the reaction of nitric oxide and superoxide. Methods for measuring the scavenging capacity of peroxynitrite usually depend on either the inhibition of tyrosine nitration or the inhibition of dihydrorhodamine 123 (DHR) oxidation to rhodamine 123 (MacDonalds-Wicks and... 

Simultaneous generation of nitric oxide and superoxide by NO synthases results in the formation of peroxynitrite. As the reaction between these free radicals proceeds with a diffusion-controlled rate (Chapter 21), it is surprising that it is possible to detect experimentally both superoxide and NO during NO synthase catalysis. However, Pou et al. [147] pointed out that the reason is the fact that superoxide and nitric oxide are generated consecutively at the same heme iron site. Therefore, after superoxide production NO synthase must cycle twice before NO production. Correspondingly, there is enough time for superoxide to diffuse from the enzyme and react with other biomolecules. 

In conclusion, it should be stressed that the competition between pro- and antiapoptotic effects of nitric oxide must probably depends on its relevant levels [137] the low physiological levels of NO principally suppress the apoptotic pathway by several mechanisms, whereas the higher rates of NO production may overcome cellar protective mechanisms and stimulate apoptosis. Furthermore, the simultaneous formation of nitric oxide and superoxide increases the possibility of apoptosis activation due to the formation of peroxynitrite. 

Kelm et al. [102] proposed a simple method of simultaneous spectroscopic detection of nitric oxide and superoxide based on NO-induced oxidation of oxyhemoglobin to methemoglobin and superoxide-mediated reduction of cytochrome c. 

Pineda-Zavela, A.P. et al., Nitric oxide and superoxide anion production in monocytes from children exposed to arsenic and lead in region Lagunera, Mexico, Toxicol. Appl. Pharmacol. 198, 283, 2004. 

Besides LPS, other particulate and soluble agents are known to stimulate the formation of eicosanoids, e.g. PGE2, PGD2, and thromboxane [57]. These agents also elicit nitric oxide and superoxide anion formation, which may help to destroy phagocytosed microorganisms or particles [58]. 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Generation of peroxynitrite in the vascular compartment as the result of ischemia/reperfusion. The introduction of oxygen following ischemia will initiate the simultaneous production of superoxide and nitric oxide. Neutrophils and macrophages may also generate nitric oxide and peroxynitrite directly. The rate of forming peroxynitrite will increase as the pnxluct of nitric oxide and superoxide concentration, and thus will increase rapidly under conditions when both are produced simultaneously. 

Matsunaga, K., and Furchgott, R. F. (1991). Responses of rabbit aorta to nitric oxide and superoxide generated by ultraviolet irradiation of solutions containing inorganic nitrite. 7- Pharmacol. Exp. Ther. 259, 1140-1146. 

It is usually believed that NO inhibits enzymes by reacting with heme or nonheme iron or copper or via the S-nitrosilation or oxidation of sulfhydryl groups, although precise mechanisms are not always evident. By the use of ESR spectroscopy, Ichimori et al. [76] has showed that NO reacts with the sulfur atom coordinated to the xanthine oxidase molybdenum center, converting xanthine oxidase into a desulfo-type enzyme. Similarly, Sommer et al. [79] proposed that nitric oxide and superoxide inhibited calcineurin, one of the major serine and threonine phosphatases, by oxidation of metal ions or thiols. 

The origin of this discrepancy is unknown. Cerielo et al. [147] studied the stimulation of apoptosis by acute hyperglycemia in working rat hearts. It was found that high glucose levels raised nitric oxide and superoxide production, which supposedly yielded peroxynitrite the last by itself or through the formation of nitrotyrosine induced apoptosis in rat hearts. 

A study has been undertaken to clarify whether glucocorticoid excess affects endothelium-dependent vascular relaxation in glucocorticoid treated patients and whether dexamethasone alters the production of hydrogen peroxide and the formation of peroxynitrite, a reactive molecule between nitric oxide and superoxide, in cultured human umbilical endothelial cells (7). Glucocorticoid excess impaired endothelium-dependent vascular relaxation in vivo and enhanced the production of reactive oxygen species to cause increased production of peroxynitrite in vitro. Glucocorticoid-induced reduction in nitric oxide availability may cause vascular endothelial dysfunction, leading to hypertension and atherosclerosis. 

Barton DFIR (1996) On the mechanism of Gif reactions. Chem Soc Rev 25 237-239 Barton DFIR (1998) Gif chemistry the present situation. Tetrahedron 54 5805-5817 Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87 1620-1624 Benson SW (1965) Bond energies. J Chem Educ 42 502-518... 

Koppenol WH (1998b) Peroxynitrite uncloaked Chem Res Toxicol 11 716-717 Koppenol WH (1999) Hydroxyl radical vs. peroxynitrite a replay. Free Rad Biol Med 26 778 Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beckmann JS (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5 834-842... 

Tsai P, Porasuphatana S, Pou S, Rosen GM (2000) Investigations into the spin trapping of nitric oxide and superoxide models to explore free radical generation by nitric oxide synthase. J Chem Soc Perkin Trans 2 983-988... 

Inoue S, Kawanishi S (1995) Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide. FEBS Lett 371 86-88... 

Peroxynitrite has been suggested to be formed from nitric oxide and superoxide in vivo. It is a highly reactive oxidant, and causes nitration on the aromatic ring of free tyrosine and protein tyrosine residues. It was reported that peroxynitrite induced various oxidative damage in vitro, for example LDL oxidation, lipid peroxidation, and DNA strand breakage [30]. 

Apparent hydroxyl radical production by peroxynitrite implications for endothelial injury from nitric oxide and superoxide, Proc. Natl. Acad. Sci. USA 87 1620-1624. 

---