Antioxidants lipid-associated

The major lipid-soluble antioxidant primarily associated with lipid membranes is a-tocopherol (vitamin E). Circulating a-tocopherol is carried by chylomicrons, LDL and HDL and also has extracellular antioxidant capacities. As a chain-breaking antioxidant, it short circuits the propagation phase of lipid peroxidation because the peroxyl radical will react with a-tocopherol more rapidly than a polyunsaturated ffitty acid (Burton and Traber, 1990). The resulting a-tocopheryl radical reacts with a second peroxyl radical to form an inactive, nonradical complex. In vitro, ascorbate regenerates the tocopheryl radical into its native non-radical form (Burton and Traber, 1990). 

The book includes an introductory overview on food factors and then perspective chapters on bioavailability of catechins and chemistry of structured and nutraceutical lipids. Subsequent sections cover signal transduction, gene modulation, biomarker, and animal model studies as affected by food bioactives. Finally, the chemistry and bioactivity of antioxidative compounds associated fruits, vegetables, and other plants are presented. 

In the last few decades, several epidemiological studies have shown that a dietary intake of foods rich in natural antioxidants correlates with reduced risk of coronary heart disease particularly, a negative association between consumption of polyphenol-rich foods and cardiovascular diseases has been demonstrated. This association has been partially explained on the basis of the fact that polyphenols interrupt lipid peroxidation induced by reactive oxygen species (ROS). A large body of studies has shown that oxidative modification of the low-density fraction of lipoprotein (LDL) is implicated... 

Dietary consumption of polyphenols is associated with a lower risk of degenerative diseases. In particular, protection of serum lipids from oxidation, which is a major step in the development of arteriosclerosis, has been demonstrated. More recently, new avenues have been explored in the capacity of polyphenols to interact with the expression of the human genetic potential. The understanding of the interaction between this heterogeneous class of compounds and cellular responses, due either to their ability to interplay in the cellular antioxidant network or directly to affect gene expression, has increased. 

As has already been stated, the carotenoids are lipophilic and are therefore absorbed and transported in association with the lipoprotein particles. In theory, this fortuitous juxtaposition of lipid and carotenoid should confer protection on the lipid through the antioxidant properties of the carotenoid. No doubt some antioxidant protection is afforded by the presence of the carotenoids derived from the diet. However, with one or two exceptions, human supplementation studies have not supported a role for higher dose carotenoid supplements in reducing the susceptibility of the low-density lipoproteins to oxidation, either ex vivo or in vivo (Wright et al, 2002 Hininger et al, 2001 Iwamoto et al, 2000). 

Caeruloplasmin (Cp) is an acute phase glycoprotein with a copper transport function. At least 90% of total plasma copper is bound to Cp with the remaining 10% associated with albumin, histidine and small peptides. Lipid peroxidation requires the presence of trace amounts of transition metals and the copper-containing active site of Cp endows it with antioxidant capacity... 

There is very little data on ROM production in haemochromatosis in humans. Increases in thiobarbituric acid reactants in plasma were associated with increases in non-transferrin-bound free iron. However, other indices of lipid peroxidation were no different from controls (Peters eta/., 1985). There are no studies of in vivo lipid peroxidation in humans. It is also of interest that levels of antioxidant defences in liver biopsies from patients with haemochromatosis are normal (Selden et /., 1980). 

Repeated periods of exercise reduce the likelihood of damage to skeletal muscle during subsequent bouts of the same form of exercise and this appears to be associated with an increase in the activity of muscle SOD (Higuchi et al. 1985), a reduced level of lipid peroxidation products during exercise in trained rats (Alessio and Goldfarb, 1988), and a modification of the concentration of antioxidants and activity of antioxidant enzymes in trained humans (Robertson etal., 1991). Packer and colleagues (Quintanilha etui., 1983 Packer, 1984) have also examined the exercise endurance of animals of modified antioxidant capacity and found that vitamin E-deficient rats have a reduced endurance capacity, while Amelink (1990) has reported that vitamin E-deficient rats have an increased amount of injury following treadmill exercise. 

Further research is required to establish whether free-radical-induced damage is a primary event in diabetes. Tissue damage, which is associated with inactivation of antioxidants and release of metal ions that are potent catalysts of free radical reactions, can lead to lipid peroxidation. This raises the possibility that the diabetic process itself or other frctors may increase free-radical activity following direct tissue damage. 

In their review some years ago, Reddy and Rao (1986) cited several lines of evidence for peroxisome-proliferation-mediated oxidative stress being associated with hepatocarcinogenesis. They mentioned the sustained increase in hydrogen peroxide production, the detectable increased levels of hydrogen peroxide in the livers of treated animals, increased lipid peroxidation associated with treatment and marked inhibition of hepatocarcinogenesis by antioxidant compounds. However, definitive studies remain to be carried out. 

Vitamins (C and E), polyphenolic compounds, and carotenoids are the main groups of antioxidants present in fruits and vegetables. Vitamins are single molecules, but polyphenols and carotenoids are made up of hundreds of compounds with a wide range of structures and molecular masses. The intake of these antioxidants can lead to sustained reduction of the kind of oxidative damage to lipids, proteins, and DNA that is associated with the development of chronic diseases (Evans and Halliwell 2001). 

The determination of F2-isoprostanes, oxidation products of arachidonic acid, has been proposed as a more reliable index of oxidative stress in vivo, overcoming many of the methodological problems associated with other markers. The isoprostanes have emerged as a most effective method of quantifying the potential of antioxidants to inhibit lipid peroxidation. However, one drawback of this method is that quantification of F2-iP requires sophisticated techniques, in particular GC/MS and HPLC/MS... 

Similar to lipids the oxidation of proteins has already been studied for more than 20 years. Before discussing the data on protein oxidation, it should be mentioned that many associated questions were already considered in previous chapters. For example, the oxidation of lipoproteins, which is closely connected with the problems of nonenzymatic lipid peroxidation was discussed in Chapter 25. Many questions on the interaction of superoxide and nitric oxide with enzymes including the inhibition of enzymatic activities of prooxidant and antioxidant enzymes are considered in Chapters 22 and 30. Therefore, the findings reported in those chapters should be taken into account for considering the data presented in this chapter. 

Chelators of iron, which are now widely applied for the treatment of patients with thalassemia and other pathologies associated with iron overload, are the intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI) (Figure 19.23, see also Chapter 31). Desferrioxamine (DFO) belongs to a class of natural compounds called siderophores produced by microorganisms. The antioxidant activity of DFO has been studied and compared with that of synthetic hydroxypyrid-4-nones (LI) and classic antioxidants (vitamin E). It is known that chronic iron overload in humans is associated with hepatocellular damage. Therefore, Morel et al. [370] studied the antioxidant effects of DFO, another siderophore pyoverdin, and hydroxypyrid-4-ones on lipid peroxidation in primary hepatocyte culture. These authors found that the efficacy of chelators to inhibit iron-stimulated lipid peroxidation in hepatocytes decreased in the range of DFO > hydroxypyrid-4-ones > pyoverdin. It seems that other siderophores are also less effective inhibitors of lipid peroxidation than DFO [371],... 

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