Superoxide production

They encapsulated poly(MA-CDA) into mannan-coated liposomes and evaluated superoxide production from mouse macrophages. The activity was three- to five-fold high compared with uncapsulated poly(MA-CDA) itself [5,11], suggesting that an increased incorporation of the polymer by the receptor-mediated endocytosis mediated the higher biological activity.. 

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). 

Boveris, A., Fraga, C.G., Varsavsky, A.I. and Koch, O.I. (1983). Increased chemiluminescence and superoxide production in the liver of chronic ethanol-treated rats. Arch. Biochem. Biophys. 227, 534-541. 

Kanerud, L., Hafttrom, 1. and Ringertz, B. (1990). Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production role of cytosolic free calcium. Ann. Rheum. Dis. 49, 296-300. 

Hiramatsu, K. and Arimori, S. (1988). Increased superoxide production by mononuclear cells of patients with hyper-triglyceridaemia and diabetes. Diabetes 37, 832-837. 

Sakurai, T. and Tsuchiya, S. (1988). Superoxide production from non-enzymatically glycated protein. FEES Lett. 236, 406-410. 

As a consequence of the inhalation of mineral dusts, infiltration into the lung of inflammatory phagocytic cells, namely PMN and macrophages, occurs (Rola-Pleszczynski et al., 1984). Analysis of the cell populations of the rat pleural cavities after injection with asbestos and silica dust also showed both degranulation and reduction of the mast cell population (Edwards etal., 1984), and it is of interest to note that histamine augments the particle-stimulated generation of macrophage superoxide production (Diaz et al., 1979). 

Sakamoto, W., Fujie, K., Handa, H., Ogihara, T. and Mino, M. (1990). In vivo inhibition of superoxide production and protein kinase C activity in macrophages from vitamin E-treated rats. Intemat. J. Vit. Nutr. Res. 60, 338-342. 

The antiulcer agent rebamipide ((2-(4-chlorobenzoy-lamino)-3-[2(lH)-quinolinon-4-yl]propionic acid) dose-dependently decreased hydroxyl radical signal generated by the Fenton reaction in an e.s.r. study. Rebamipide is active as a hydroxyl radical scavenger and inhibitor of superoxide production by neutrophils (Yoshikawa etal., 1993). 

H.A. Kontos and E.P. Wei, Superoxide production in experimental brain injury. J. Neurosurgery. 64,... 

C.J. McNeil, K.R. Greenough, P.A. Weeks, and C.H. Self, Electrochemical sensors for direct reagentless measurement of superoxide production by human neutrophils. Free Rad. Res. Comm. 17, 399-406 (1992). 

It has already been stressed that the discovery of superoxide as the enzymatically produced diffusion-free dioxygen radical anion [1-3] was a pivotal event in the study of free radical processes in biology. It is not of course that the McCord and Fridovich works were the first ones in free radical biology, but the previous works were more of hypothetical character, and only after the identification of superoxide by physicochemical, spectral, and biochemical analytical methods the enzymatic superoxide production became a proven fact. 

The inactivation of enzymes containing the zinc-thiolate moieties by peroxynitrite may initiate an important pathophysiological process. In 1995, Crow et al. [129] showed that peroxynitrite disrupts the zinc-thiolate center of yeast alcohol dehydrogenase with the rate constant of 3.9 + 1.3 x 1051 mol-1 s-1, yielding the zinc release and enzyme inactivation. Later on, it has been shown [130] that only one zinc atom from the two present in the alcohol dehydrogenase monomer is released in the reaction with peroxynitrite. Recently, Zou et al. [131] reported the same reaction of peroxynitrite with endothelial NO synthase, which is accompanied by the zinc release from the zinc-thiolate cluster and probably the formation of disulfide bonds between enzyme monomers. The destruction of zinc-thiolate cluster resulted in a decrease in NO synthesis and an increase in superoxide production. It has been proposed that such a process might be the mechanism of vascular disease development, which is enhanced by diabetes mellitus. 

To study the effects of iron overloading on inflammatory cells, Muntane et al. [186] investigated the effect of iron dcxtran administration on the acute and chronic phases of carrageenan-induced glanuloma. It was found that iron dcxtran increased the iron content in plasma and stores, and enhanced lipid peroxidation and superoxide production by inflammatory cells. At the same time, iron dcxtran had a beneficial effect on recovery from the anemia of inflammation. It has been suggested that iron overload may affect nitric oxide production in animals. For example, alveolar macrophages from iron-overloaded rats stimulated with LPS or interferon-7 diminished NO release compared to normal rats [187]. 

As seen from the above scheme, XO reduces dioxygen into hydrogen peroxide by two-electron reduction mechanism and into superoxide by one-electron reduction mechanism. The efficiency of superoxide production depends on the nature of the substrate (in addition to... 

At the beginning only XO and not XDH was considered as a superoxide producer. For example, in 1985 McCord [19] suggested that the conversion of XDH into XO is responsible for an increase in superoxide production in postischemic reperfusion injury. However, it has later been shown [20,21] that XDH itself is a producer of superoxide although not so effective as XO. Moreover, the efficiency of superoxide production differs for different types of the enzyme. Thus, 2.8 to 3.0 mol of superoxide were produced by chicken liver XDH, while superoxide production by bovine milk XDH was insignificant [21]. Sanders et al. [22] found that NADH oxidation by human milk and by bovine milk XDHs catalyzed superoxide production more rapidly than XO this process was inhibited by NAD and diphenyleneiodo-nium but not by the established XO inhibitors allopurinol and oxypurinol. 

Competition between dioxygen and quinones depends on the one-electron reduction potentials of quinones [29], and therefore, quinones may inhibit or stimulate superoxide production. 

It is extremely important that the interaction of quinones with XO (Reaction (3)) is reversible that can lead to receiving erroneous results at the measurement of superoxide production by SOD-inhibitable cytochrome c reduction [28,29] (see also Chapter 27). Lusthof et al. [30] demonstrated that 2,5-bis(l-aziridinyl)-l,4-benzoquinones are directly reduced by XO. Interestingly at quinone concentrations greater than 25pmol I 1, quinones entirely suppressed one-electron reduction of dioxygen, and cytochrome c was completely reduced by the semiquinones formed. It is well known that cytochrome c and lucigenin are effective superoxide scavengers and due to that, these compounds are widely used in the quantitative assays of superoxide detection. Nonetheless, under certain experimental conditions they can be directly reduced by XO [31]. 

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