Copper induced LDL oxidation

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. 

Ashton, E.L., Dalais, F.S., and Ball, M.J. 2000. Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation. JAm Coll Nutr 19, 761-767. 

Red wine contains quercetin, rutin, catechin, and epicatechin, among other flavonoids (Frankel and others 1993). Quercetin and other phenolic compounds isolated from wines were found to be more effective than a-tocopherol in inhibiting copper-catalyzed LDL oxidation. It has been determined that quercetin has also several anti-inflammatory effects it inhibits inflammatory cytokine production (Boots and others 2008), inducible NO synthase expression and activation of inflammatory transcription factors (Hamalainen and others 2007), and activity of cyclooxygenase and lipooxygenase (Issa 2006), among others. 

It has also been shown that LDL oxidation is increased in diabetes. In this connection, Mowri et al. [179] studied the effect of glucose on metal ion-dependent and -independent LDL oxidation. They found that pathophysiological glucose concentrations enhanced copper- and iron-induced LDL oxidation measured via the formation of conjugated dienes. In contrast, glucose had no effect on metal-independent free radical LDL oxidation. Correspondingly,... 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

Flavonoids exhibit protective action against LDL oxidation. It has been shown [145] that the pretreatment of macrophages and endothelial cells with tea flavonoids such as theaflavin digallate diminished cell-mediated LDL oxidation probably due to the interaction with superoxide and the chelation of iron ions. Quercetin and epicatechin inhibited LDL oxidation catalyzed by mammalian 15-lipoxygenase, and are much more effective antioxidants than ascorbic acid and a-tocopherol [146], Luteolin, rutin, quercetin, and catechin suppressed copper-stimulated LDL oxidation and protected endogenous urate from oxidative degradation [147]. Quercetin was also able to suppress peroxynitrite-induced oxidative modification of LDL [148],... 

Figure 8.3 Pomegranate juice consumption reduces serum and LDL oxidation in humans and in atherosclerotic E° mice. Mean ( SD) effect of 2 and 9 weeks of PJ supplementation to 13 healthy men and to E° mice (A and B, respectively) on the susceptibility of serum to radical-induced lipid peroxidation and copper ion-induced LDL oxidation (C and D, respectively) is shown. = p < 0.01 (after vs. before PJ consumption in humans, and PJ vs. control in mice).

Lapenna et al. (1998) found that ticlopidine, a thienopyridine characterised by lipophilic properties, at therapeutically relevant concentrations (2.5-10 pM), but neither aspirin nor salicylate, significantly counteracted copper-driven human LDL oxidation. Ticlopidine, at 5 and 10 pM, was also antioxidant on peroxyl radical-induced LDL oxidation yet it was ineffectual on thiol and ascorbate oxidation mediated by peroxyl radicals themselves, suggesting that drug antioxidant capacity is somehow related to the lipoprotein nature of the oxidiz-able substrate, but not to radical scavenging. The drug could not indeed react with the stable free radical l,l-diphenyl-2-picrylhydrazyl, not had apparent metal complexing-inactivating activity. 

Figure 4, Time course of copper (II) induced LDL oxidation. Oxidation ofLDL (50 pg/mL) was induced by Cu (5.0 pM) at 25 C. Conjugated diene formation was monitored continuously by the increase of absorption at 234 nm. Probucol and trolox were used as positive control...

Oxidation of LDL plays an important role in the development of atherosclerosis. Turmeric extract decreased the susceptibility of LDL to lipid peroxidation, thus suggesting its value in the management of cardiovascular disease (Ramirez-Tortosa et al. 1999). In healthy hiunans, the daily intake of 200 mg of turmeric extract resulted in a decrease in total blood lipid peroxides as well as in HDL- and LDL-lipid peroxidation (Miquel et al. 2002). The beneficial influence of dietary curciunin on the susceptibility of LDL to oxidation was examined in an animal study. Dietary curcumin significantly inhibited the in vivo iron-induced LDL oxidation as well as copper-induced oxidation of LDL in vitro (Manjunatha and Srinivasan 2006). 

Tea extracts and tea polyphenols inhibit copper- and peroxide-induced oxidation of LDL in vitro (116,123,124). The inhibitory concentration for 50% reduction (IC q) values for inhibition of copper-induced oxidation of LDL by some phenoHc antioxidants are Hsted in Table 7. The IC q for epigaHocatechin gaHate was found to be 0.075 p.mM, which was the most potent of all the phenoHc antioxidants tested (123,124). Similar results have been reported elsewhere (115,116,125,126). 

Consumption of PJ for 1 and 2 weeks by healthy volunteers increased the resistance of their LDL to copper ion-induced oxidation, as shown by a prolongation of the lag time required for the initiation of LDL oxidation, by 29 and 43%, in comparison to LDL obtained prior to juice consumption (Figure 8.3C).28 Similarly, the resistance of their high-density lipoprotein (HDL) to copper ion-induced oxidation also gradually increased after PJ consumption, as shown by a prolongation in the... 

This was demonstrated by reduced formation of lipid peroxides in LDL during its incubation with copper ions (by 40,49, 57, and 59% after 3,6,9, and 12 months of PJ consumption, respectively). PJ consumption also decreased the propensity of LDL derived from E° mice to copper ion-induced oxidation (Figure 8.3D). In E° mice that consumed 6.25 or 12.5 pi. /day of PJ concentrate for a period of 2 months, LDL oxidation was delayed by 100 and 120 minutes, respectively, in comparison to LDL obtained before juice administration. Determination of the extent of LDL oxidation by the TB AR assay revealed a significant inhibition after PJ consumption (Figure 8.3D). Furthermore, the progressive increase with age in the susceptibility of the mice LDL to oxidation was significantly attenuated by PJ consumption in a dose-dependent manner.28... 

Jin and collaborators reported the antioxidant activity of cleomiscosins A (9) and C (7), isolated from the leaves and twigs of Acer okamotoatum (19). Compound 7 inhibited LDL oxidation mediated by either catalytic copper ions or free radicals generated with 2,2 -azobis(2-amidinopropane) dihydrochloride, in a dose-dependent manner. By means of electrophoretic analysis it was also observed that 7 protected apolipoprotein B-lOO against Cu fragmentation. Also, fluorescence analysis clearly indicated that both 7 and 9 protect against the oxidative modification of apoB-100, induced by either Cu + or HOCl. Compounds 7 and 9 could, therefore, be beneficial in preventing LDL oxidation in atherosclerotic lesions. 

Spray-dried elderberry juice with high amounts of anthocyanin glucosides caused prolongation of the lag phase of copper induced oxidation of human LDL, while the maximum oxidation rate remained unchanged (Abuja et al., 1998). For peroxyl-radical-driven LDL oxidation, however, both prolongation of lag time and reduction of maximum oxidation rate occurred. When the extract was added after LDL oxidation was initiated, the elderberry extract demonstrated a pro-oxidative action. The pro-oxidative effect was more pronounced the longer the LDL oxidation was allowed to proceed before the extract was added. 

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