Superoxide vitamin

Under aqueous conditions, flavonoids and their glycosides will also reduce oxidants other than peroxyl radicals and may have a role in protecting membranal systems against pro-oxidants such as metal ions and activated oxygen species in the aqueous phase. Rate constants for reduction of superoxide anion show flavonoids to be more efficient than the water-soluble vitamin E analogue trolox (Jovanovic et al, 1994), see Table 16.1. 

The heart has a relatively low catalase activity, which, together with the superoxide dismutase (SOD) system, acts to remove hydrogen peroxide and superoxide radicals. In addition, in man, dietary vitamin C plays an important role in the reduction of vitamin E, an intrinsic antioxidant component of biological membranes (Chen and Thacker, 1986 Niki, 1987). Both vitamins C and E can also react directly with hydroxyl and superoxide radicals (HalliwcU and Gutteridge, 1989 Meister, 1992). 

Figure 4.8 Reduction of Na/K ATPase activity in isoiated guinea-pig hearts subjected to ischaemia/reperfusion and its prevention by various agents control non-ischaemic hearts (Nl) guinea-pig hearts subjected to global ischaemia for 2 h and subsequently reperfused for 1 h (IR). In other preparations, superoxide dismutase (SOD) 100 U/ml, catalase (CAT) 150 U/ml, dimethylsulphoxide (DMS) 50 mu, histidine (HIS) 10 mu, vitamin E (TOC)...

Reduced scavenger capacity is deduced from studies demonstrating low plasma and cellular levels of antioxidants such as glutathione, vitamin E, thiols, magnesium and ascorbic acid, as well as reduced levels of scavenger enzymes such as neutrophil glutathione peroxidase and red cell superoxide dismutase (Lyons, 1991 Sinclair /., 1992). 

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. 

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

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

Vitamin A (retinol) is not a classic antioxidant although it is frequently related to a group of antioxidant vitamins E, C, and A. Murata and Kawanishi [83] found that retinol and its derivative retinal induced the formation of 8-HOdG in HL-60 cells. This process was supposedly mediated by hydroxyl radicals formed from hydrogen peroxide (the product of superoxide dismutation) and endogenous transition metal ions. 

Antioxidant activity of flavonoids has already been shown about 40 years ago [90,91]. (Early data on antioxidant flavonoid activity are cited in Ref. [92].) Flavonoids are polyphenols, and therefore, their antioxidant activity depends on the reactivity of hydroxyl substituents in hydrogen atom abstraction reactions. As in the case of vitamins E and C, the most studied (and most important) reactions are the reactions with peroxyl radicals [14], hydroxyl radicals [15], and superoxide [16]. 

Since glutathione is synthesized in cells in relatively huge amounts, it is seldom applied as pharmacological antioxidant. Furthermore, the mechanism of its antioxidant activity is not so simple as that of vitamins E and C. The major reason is that the GS radical formed during scavenging of free radicals by GSH does not disappear by dimerization but participates in the chain reaction, producing superoxide (Reactions (20)-(23)). Furthermore, it has recently been shown that contrary to previous findings the rate constant for the reaction of GSH with superoxide is relatively small (200-1000 lmol-1 s-1) [211,223],... 

In the case of ubiquinones we have already considered the ability of quinones to react with superoxide and other free radicals. Naphthoquinones, vitamin K and its derivatives, especially menadione, are the well known producers of superoxide through redox cycling with dioxygen. However, in 1985, Canfield et al. [254] have shown that vitamin K quinone reduced the oxidation of linoleic acid while vitamin K hydroquinone stimulated lipid peroxidation. Surprisingly, later on, conflicting results were reported by Vervoort et al. [255] who found that only hydroquinones of vitamin K and its analogs inhibited microsomal lipid peroxidation. 

Vitamin B6 (pyridoxine) and its derivative pyridoxamine are apparently able to inhibit superoxide production, reduce lipid peroxidation and glycosylation in high glucose-exposed erythrocytes [353], It was suggested that the suppression of oxidative stress in erythrocytes may be a new mechanism by which these natural compounds inhibit the development of complication in diabetes mellitus. 

The possible involvement of free radicals in the development of hypertension has been suspected for a long time. In 1988, Salonen et al. [73] demonstrated the marked elevation of blood pressure for persons with the lowest levels of plasma ascorbic acid and serum selenium concentrations. In subsequent studies these authors confirmed their first observations and showed that the supplementation with antioxidant combination of ascorbic acid, selenium, vitamin E, and carotene resulted in a significant decrease in diastonic blood pressure [74] and enhanced the resistance of atherogenic lipoproteins in human plasma to oxidative stress [75]. Kristal et al. [76] demonstrated that hypertention is accompanied by priming of PMNs although the enhancement of superoxide release was not correlated with the levels of blood pressure. Russo et al. [77] showed that essential hypertension patients are characterized by higher MDA levels and decreased SOD activities. 

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