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Mechanisms and Biomarkers (WG 4) page 45<br />

__________________________________________________________________________________________<br />

Carotenoid Concentration and Interaction with Other Antioxidants - Many dietary<br />

intervention studies that have employed high concentrations of carotenoids, failed to report<br />

any effects. This has also been reported for other antioxidants such as vitamin E. Killion and<br />

colleagues (1996) reported that patients suffering atherosclerosis exhibited altered levels of<br />

vitamin E. Their data also demonstrates a strong association between tissue vitamin E levels<br />

and tissue lipid peroxidation. Similar results were obtained when rats were fed with large<br />

amounts of β-carotene, increased concentrations of peroxides were found in the rat plasma<br />

and liver.<br />

Any effective synergism between the carotenoids, xanthophylls, tocopherols and other cooxidants<br />

would depend upon a balance between all of these components. An increase in<br />

carotenoid concentration could disturb this balance and promote lipid peroxidation. The<br />

induction of lipid peroxidation would generate carotenoid radical adducts. The prevention of<br />

any prooxidant activity would therefore depend upon the ability of tocopherols to reduce the<br />

radicals, and the regeneration of the tocopherols by water soluble antioxidants. Therefore an<br />

increase in the carotenoid concentration or a decrease in associated antioxidants would<br />

enhance the probability of prooxidant activity.<br />

Another untoward effect of an increased concentration of carotenoids is the destabilisation of<br />

plasma membranes. van De Ven (1984) and colleagues showed that when β-carotene was<br />

incorporated into phosphatidylcholine membranes, the orientation of the carotenoid was<br />

dependent upon the composition of the lipid bilayers. In the case of dioleyl lecithin bilayers<br />

the carotenoids had a parallel orientation and a perpendicular orientation was observed in a<br />

soybean lecithin lamellar membranes. The addition of β-carotene to phosphatidylcholine<br />

membranes decreased the rigidity of the membrane by increasing the motional freedom of the<br />

polar lipid headgroups. β-Carotene is distributed homogeneously with a membrane with no<br />

preferred orientation, thus its effect is to decrease the rigidity of the membrane. Whereas,<br />

xanthophylls would behave as ‘gate posts’ spanning the entire membrane bilayer. This<br />

rigidifying effect would decrease the penetration of oxygen in the lipid bilayer. This in turn<br />

would then limit the extent of lipid peroxidation.<br />

Recently lutein and zeaxanthin were incorporated by Sujak (1999) into phosphatidylcholine<br />

liposomes. The liposomes were then challenged with either UV or AAPH (2,2’-azobis(2methylpropionamidine)dihydrochloride).<br />

The conclusions of this study indicated that there<br />

was a decreased penetration barrier for the oxidant AAPH, and the xanthophylls acted by free<br />

radical scavenging mechanisms to protect the liposomes against against oxidative damage.

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