Superoxide generator

Rowley, D.A. and Halliwell, B. (1983). DNA damage by superoxide-generating systems in relation to the mechanism of action of the anti-tumor antibiotic adriamycin. Biochim. Biophys. Acta 761, 86-93. 

Meltzer, S., Goldberg, B., Lad, P. and Easton, J. (1989). Superoxide generation and its modulation by adenosine in neutrophils of subjects with asthma. J. Allergy Clin. Immunol. 83, 960-966. 

Thomas, P.D., Mao, G.D., Rabinovitch, A. and Posnansky, M.J. (1993). Inhibition of superoxide generating NADPH oxidase of human neutrophils by lazaroids. Biochem. Pharmacol. 45, 241-251. 

It has been proposed that the capacity of antiinflammatory drugs to scavenge and inhibit ROM production is pertinent to their therapeutic effect (Hal-hwell et al., 1988). NSAIDs, namely indomethacin, inhibit superoxide generation by stimulated guinea-pig macrophages (Oyanagui, 1976) and the scavenging effects of PMN-derived ROMs by the sulphasalazine... 

Edwards, S.W. and Lloyd, D. (1988). The relationship between superoxide generation, cytochrome b and oxygen in activated neutrophils. FEES Lett. 227, 39-42. 

Murata, M and Kawanishi, S, 2000. Oxidative DNA damage by vitamin A and its derivative via superoxide generation. J Biol Chem 275, 2003-2008. 

C.M. Tolias, J.C. McNeil, J. Kazlauskate, and E.W. Hillhouse, Superoxide generation from constitutive nitric oxide synthase in astrocytes in vitro regulates extracellular nitric oxide availability. Free Radical Biol. Med. 26, 99-106 (1999). 

The principle of antioxidant detection is shown in Fig. 17.3. Superoxide was enzymatically produced and dismutated spontaneously to oxygen and H202. Under controlled conditions of superoxide generation such as air saturation of the buffer, optimal hypoxanthine concentration (100 pM) and XOD activity (50mU ml-1) a steady-state superoxide level could be obtained for several min (580-680 s). Since these steady-state superoxide concentrations can be detected by the cyt c-modified gold electrode, the antioxidate activity can be quantified from the response of the sensor electrode by the percentage of the current decrease. 

Harbour, J.R. and Hair, M.L., Superoxide generation in the photolysis of aqueous cadmium sulphide dispersions, detection by spin trapping, /. Phys. Chem., 81,1791,1977. 

However, Goldstein and Czapski [123] believe that in this reaction a genuine attacking species is hydroxyl radical, which reacts with NADH without superoxide generation. 

CL produced in the presence of exogenous NADPH or NADH, which has been studied in Refs. [97,100], may originate from other sources than superoxide generation [90]. In our opinion [98], the data obtained on the basis lucigenin CL measurement, especially with the use of small lucigenin concentrations provide the reliable estimate of superoxide concentration while the use of ESR spin technique underestimates it, particularly in vascular tissue and cells (see Chapter 32). 

Complex I can be regulated by phosphorylation. Demin et al. [28] studied superoxide generation by Complex III using the kinetics model of electron transfer from succinate to cytochrome c. 

Superoxide generation was detected via the NADPH-dependent SOD-inhibitable epinephrine oxidation and spin trapping [15,16], Grover and Piette [17] proposed that superoxide is produced equally by both FAD and FMN of cytochrome P-450 reductase. However, from comparison of the reduction potentials of FAD (-328 mV) and FMN (190 mV) one might expect FAD to be the most efficient superoxide producer. Recently, the importance of the microsomal cytochrome h558 reductase-catalyzed superoxide production has been shown in bovine cardiac myocytes [18]. 

Then, A-hydroxyphentermine supposedly reacts with superoxide generated by NADPH-cytochrome P-450 reductase and forms the final product 2-methyl-2-nitro-l-phenylpropane ... 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Treatment of RA patients with various drugs was shown to affect free radical production by phagocytic cells. It was found that the therapy with gold compounds [252] and piroxicam [237] diminished superoxide production in RA patients. Surprisingly, Hurst et al. [253] reported that successful therapy with penicillamine or sodium aurothiomalate is accompanied by an increase in superoxide production and serum thiol levels. The mechanism of this phenomenon is unknown. Mur et al. [254] demonstrated that antirheumatic medication of RA patients caused reducing cytokine priming of superoxide generation. 

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