Biologic activity of carotenoids related to distinct membrane physicochemical interactions.
Carotenoids are naturally occurring organic pigments that are believed to have therapeutic benefit in treating cardiovascular disease (CVD) because of their antioxidant properties. However, prospective randomized trials have failed to demonstrate a consistent benefit for the carotenoid beta-carotene in patients at risk for CVD. The basis for this apparent paradox is not well understood but may be attributed to the distinct antioxidant properties of various carotenoids resulting from their structure-dependent physicochemical interactions with biologic membranes. To test this hypothesis, we measured the effects of astaxanthin, zeaxanthin, lutein, beta-carotene, and lycopene on lipid peroxidation using model membranes enriched with polyunsaturated fatty acids. The correlative effects of these compounds on membrane structure were determined using small-angle x-ray diffraction approaches. The nonpolar carotenoids, lycopene and beta-carotene, disordered the membrane bilayer and stimulated membrane lipid peroxidation (>85% increase in lipid hydroperoxide levels), whereas astaxanthin (a polar carotenoid) preserved membrane structure and exhibited significant antioxidant activity (>40% decrease in lipid hydroperoxide levels). These results suggest that the antioxidant potential of carotenoids is dependent on their distinct membrane lipid interactions. This relation of structure and function may explain the differences in biologic activity reported for various carotenoids, with important therapeutic implications.
McNulty
Hyesun
H
Elucida Research, Beverly, MA 01915, USA.
Jacob
Robert F
RF
Mason
R Preston
RP
D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D014975:Lutein / Q000494:pharmacology; D000077276:Lycopene; D018384:Oxidative Stress / Q000187:drug effects; D024341:Xanthophylls / Q000494:pharmacology; D065146:Zeaxanthins; D019207:beta Carotene / Q000494:pharmacology
D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene; D002338:Carotenoids; C005948:astaxanthine; D000077276:Lycopene; D014975:Lutein