Xanthine oxidase , inhibitory effects

In addition to xanthine oxidase, flavonoids are able to inhibit the activity of a wide range of enzymes. These inhibitory effects of flavonoids may depend both on their free radical scavenging and chelating properties. Thus, it has been shown that flavonoids inhibit... 

Superoxide-dismuting activity of copper rutin complex was confirmed by comparison of the inhibitory effects of this complex and rutin on superoxide production by xanthine oxidase and microsomes (measured via cytochrome c reduction and by lucigenin-amplified CL, respectively) with their effects on microsomal lipid peroxidation [166]. An excellent correlation between the inhibitory effects of both compounds on superoxide production and the formation of TBAR products was found, but at the same time the effect of copper rutin complex was five to nine times higher due to its additional superoxide dismuting capacity. 

Values (p.mol I-1) for Inhibitory Effects of Metal-Rutin Complexes and Rutin on Cytochrome c Reduction by Xanthine Oxidase (I), Iron-Catalyzed Microsomal Lipid Peroxidation (II), and Lucigenin-Amplified Microsomal CL (III) [167]... 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

Hatano, T. et al., Effects of interactions of tannins with co-existing substances. VII. Inhibitory effects of tannins and related polyphenols on xanthine oxidase, Chem. Pharm. Bull., 38, 1224, 1990. 

Aryl-8-azaadenines 300, 8-azahypoxanthine 301, and 6-thiolo-8-azapurines 302 were tested for their inhibitory effect on adenosine deaminase, guanine deaminase, and xanthine oxidase from mammalian sources. Compounds 300 were the most efficient inhibitors of adenosine deaminase and... 

The inhibitory effects of tea polyphenols on xanthine oxidase (XO) were investigated. Theaflavins and EGCG inhibit XO to produce uric acid and also act as scavengers of superoxide. Theaflavin 3,3 -digaUate (TE-3) acts as a competitive inhibitor and is the most potent inhibitor of XO among these compounds. TE-3 also inhibited the superoxide production in HL-60 cells. Therefore, the antioxidative activity of tea polyphenols is due not only to their ability to scavenge superoxides but also to their ability to block XO and relative oxidative signal transducers. ... 

Lin, J.K. and Shih, C.A., Inhibitory effect of curcumin on xanthine dehydroge-nase/oxidase induced by TPA in NIH3T3 cells. Carcinogenesis, 15, 1717, 1994. 

Xanthine oxidase is a rather nonspecific enzyme it not only catalyzes the oxidation of hypoxanthine and xanthine, but also the conversion of adenine to 2,8-dihydroxyadenine (B23, K9) as well as the oxidation of many unusual purines, such as 2-azaadenine (S14). It also acts on xanthopterin (K4), and catalyzes the oxidation of a variety of aldehydes and NADH. Several pterins, notably 2-amino-4-hydroxy-6-formyl- (K3), 2-amino-4-hydroxy-6-carboxy-, 2-amino-4-hydroxy-, and 6-hydroxymethyl- (P3) pterins, inhibit xanthine oxidase. A variety of purines are both substrate and inhibitor of the enzyme. Antabuse (tetraethylthiuram disulfide) has a considerable inhibitory effect on xanthine oxidase in rat... 

All the inhibitions reported so far indicate that there is no known specific inhibitor for the manganese superoxide dismutase. The enzyme from B. stearothermophilus was found to be inhibited by cacodylate (Thornalley et al., 1982) however, the inhibition could only be observed in the xanthine/xanthine oxidase assay and not in the pulse radiolysis assay. No evidence was obtained that cacodylate could be competing with the enzyme for because little or no inhibition was observed when the copper/zinc rather than the manganese enzyme was assayed in the presence of cacodylate. Further investigations revealed that the inhibitory effect is due to a cacodylate anion radical produced by the interaction of hydroxyl radicals (generated by the xanthine/xanthine oxidase reaction) and cacodylate anions. A radical of pamoic acid (4,4 -methylenebis-(3-... 

We then examined the inhibitory effects of nobiletin on differentiated HL-60 cells, known to generate 02 - with TPA stimulation and compared them with those of luteolin. As shown in Figure 6, nobiletin exhibited a much higher level of inhibition than luteolin, while the IC50 value of nobiletin (1.2 pM) was approximately 8 times lower than that of luteolin (9.8 pM). Because nobiletin did not significantly scavenge O2 generated from the xanthine/xanthine oxidase system nor inhibited xanthine oxidase activity up to a concenPation of 500 pM (data not shown), it may inhibit the assembly or activity of multicomponent NADPH oxidase system in differentiated HL-60 cells. 

The flavones and catechins seem to be the most powerful flavonoids for protecting the body against ROS. Epicatechin and rutin are also powerful free-radical scavengers. Xanthine oxidase enzyme is a source of oxygen-free radicals. The scavenging ability of rutin, quercetin, and silibin may be due to its inhibitory effect on xanthine oxidase activity, thereby resulting in decreased oxidative injury [60]. 

Hatano, T, T. Fukuda, Y.-Z. Liu, T. Noro, and T. Okuda Phenolic Constituents of Licorice. 4. Correlation of Phenolic Constituents and Licorice Specimens from Various Sources, and Inhibitory Effects of Licorice Extracts on Xanthine Oxidase and Monoamine Oxidase. Yakugaku Zasshi, 111, 311 (1991). 

Synthetic benzophenones as 2,2 ,4,4 -tetrahydro-benzophenone, 3,4,5,2 ,3 ,4 -hexahydrobenzophe-none and 4,4 -dihydrobenzophenone displayed their inhibitory effects on xanthine oxidase with an order of activity of IC50 = 47.59,69.40 and 82.94 (JiM, respectively (Sheu et al. 2000). The apparent inhibition constant of 3,4,5,2 ,3 ,4 -hexahydrobenzophe-... 

Esculetin, umbeUiferone (7-hydroxycoumarin) and 7-hydroxy-4-methyl coumarin are strong xanthine oxidase inhibitors (Chang and Chiang 1995). The structure of 7-hydroxy coumarin plays a very important role in xanthine oxidase inhibition, the 6-hydroxy group present in the molecule of 7-hydroxy coumarin, e.g. esculetin enhanced the activity, whereas substitution by the 6-methoxy group, e.g. scopoletin (formula [47]), reduced the inhibitory effect. (Chang and Chiang 1995). 

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