Low-density lipoprotein antioxidants

Fe(lll) masking, 669 low-density lipoprotein antioxidant, 611 Prochiral alkenes... 

H. Est auer, R. Schmidt and M. Hayn, Relationships Among Oxidation of Low-Density Lipoprotein, Antioxidant Protection, and Atherosclerosis. In H. Sies (ed.) Advances in Pharmacology Antioxidants in Disease Mechanisms and Therapy. Academic Press Inc., London, 1997 vol. 38, pp.425-455. 

E. Ferguson, N. Hogg, W. A. Antholine, J. Joseph, R. J. Singh, S. Parthasarathy, and B. Kalyanaraman, Characterization of the Adduct Formed from the Reaction Between Homocystein Thiolactone and Low-Density Lipoprotein Antioxidant Implications, Free Radical Biology and Medicine 26 (199 ) 968-977. 

Chang S, Tan C, Frankel EN, Barrett DM (2000) Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars. J Agric Food Chem 48 147-151... 

Hwang, J, Hodis, H and Sevanian, A (2001) Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J. Agric. Food Chem., 49, 308-314. 

KAPLAN M and AVIRAM M (1999) Oxidized low density lipoprotein atherogenic and proinflammatoiy characteristics during macrophage foam cell formation. An inhibitory role for nutritional antioxidants and serum paraoxonase Clinical Chemistry Laboratory Medicine 37,111-9,1. 

The antioxidant activities of carotenoids and other phytochemicals in the human body can be measured, or at least estimated, by a variety of techniques, in vitro, in vivo or ex vivo (Krinsky, 2001). Many studies describe the use of ex vivo methods to measure the oxidisability of low-density lipoprotein (LDL) particles after dietary intervention with carotene-rich foods. However, the difficulty with this approach is that complex plant foods usually also contain other carotenoids, ascorbate, flavonoids, and other compounds that have antioxidant activity, and it is difficult to attribute the results to any particular class of compounds. One study, in which subjects were given additional fruits and vegetables, demonstrated an increase in the resistance of LDL to oxidation (Hininger et al., 1997), but two other showed no effect (Chopra et al, 1996 van het Hof et al., 1999). These differing outcomes may have been due to systematic differences in the experimental protocols or in the populations studied (Krinsky, 2001), but the results do indicate the complexity of the problem, and the hazards of generalising too readily about the putative benefits of dietary antioxidants. 

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). 

CARBONNEAU M-A, LEGER c L, MONNIER L (1997) Supplementation with wine phenolic compormds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu -oxidizability possible explanation by phenolic location, European Journal of Clinical Nutrition, 51, 682-90. 

There has been some evidence of a higher antioxidant effect when both flavonoids and a-tocopherol are present in systems like LDL, low-density lipoproteins (Jia et al., 1998 Zhu et al, 1999). LDL will incorporate a-tocopherol, while flavonoids will be present on the outside in the aqueous surroundings. A similar distribution is to be expected for oil-in-water emulsion type foods. In the aqueous environment, the rate of the inhibition reaction for the flavonoid is low due to hydrogen bonding and the flavonoid will not behave as a chain-breaking antioxidant. Likewise, in beer, none of the polyphenols present in barley showed any protective effect on radical processes involved in beer staling, which is an oxidative process (Andersen et al, 2000). The polyphenols have, however, been found to act synergistically... 

Gieseg, S.P., Maghzal, G., and Glubb, D., Protection of erythrocytes by the macrophage synthesized antioxidant 7,8 dihydroneopterin. Free Radic. Res., 34, 123, 2001. Gieseg, S.P. and Cato, S., Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin, Redox Rep., 8, 113, 2003. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Kim, H.S. and Lee, B.M., Protective effects of antioxidant supplementation on plasma lipid peroxidation in smokers, J. Toxicol. Environ. Health A, 63, 583, 2001. Gaziano, J.M. et al.. Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. Atherosclerosis, 112, 187, 1995. Sutherland, W.H.F. et al.. Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients, Clin. Nephrol, 52, 30, 1999. 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

Carew, T.E., Schwenke, D.C. and Steinberg, O. (1987). Antiatherogenic effect of probucol unrelated to its hyper-cholesterolaemic effect evidence that antioxidants in vim can selectively inhibit low density lipoprotein degradation in macroph -rich fatty streaks slowing the progression of atherosclerosis in the WHHL rabbit. Proc. Natl Acad. Sci. USA 84, 7725-7729. 

Esterbauer, H., Gebicki, J. Puhl, H. and Jurgens, G. (1992), The role of lipid peroxidation and antioxidants in oxidative modification of low density lipoprotein. Free Rad. Biol. Med. 13, 341-390. 

Gebicki, J.M., Jurgens, G. and Esterbauer, H. (1991). Oxidation of low-density lipoprotein in vitro. In Oxidative Stress, Oxidants and Antioxidants (ed. H. Sies) pp. 371-397. Academic Press, London. 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Heinonen IM, Meyer AS and Frankel EN. 1998. Antioxidant activity of berry phenolics on human low-density lipoprotein and liposome oxidation. J Agric Food Chem 46 4107 1112. 

This method is also used to measure ex vivo low-density lipoprotein (LDL) oxidation. LDL is isolated fresh from blood samples, oxidation is initiated by Cu(II) or AAPH, and peroxidation of the lipid components is followed at 234 nm for conjugated dienes (Prior and others 2005). In this specific case the procedure can be used to assess the interaction of certain antioxidant compounds, such as vitamin E, carotenoids, and retinyl stearate, exerting a protective effect on LDL (Esterbauer and others 1989). Hence, Viana and others (1996) studied the in vitro antioxidative effects of an extract rich in flavonoids. Similarly, Pearson and others (1999) assessed the ability of compounds in apple juices and extracts from fresh apple to protect LDL. Wang and Goodman (1999) examined the antioxidant properties of 26 common dietary phenolic agents in an ex vivo LDL oxidation model. Salleh and others (2002) screened 12 edible plant extracts rich in polyphenols for their potential to inhibit oxidation of LDL in vitro. Gongalves and others (2004) observed that phenolic extracts from cherry inhibited LDL oxidation in vitro in a dose-dependent manner. Yildirin and others (2007) demonstrated that grapes inhibited oxidation of human LDL at a level comparable to wine. Coinu and others (2007) studied the antioxidant properties of extracts obtained from artichoke leaves and outer bracts measured on human oxidized LDL. Milde and others (2007) showed that many phenolics, as well as carotenoids, enhance resistance to LDL oxidation. 

Gonsalves B, Landbo AK, Let M, Silva AP, Rosa E and Meyer AS. 2004. Storage affects the phenolic profiles and antioxidant activities of cherries (Prunus avium L.) on human low-density lipoproteins. J Sci Food Agric 84(9) 1013-1020. 

Meyer AS, Yi OS, Pearson DA, Waterhouse AL and Frankel EN. 1997. Inhibition of human low-density lipoprotein oxidation in relation to composition of phenolic antioxidants in grape (Vitis vinifera). J Agric Food Chem 45(5) 1638-1643. 

Oxidized low-density lipoprotein (LDL) may play a key role in the initiation and progression of atherosclerosis. Risk factors for elevated levels of oxidized LDL are not well established and may be important in identifying individuals who may benefit from antioxidant supplementation or interventions to reduce oxidant stress. 

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