McNulty Hyesun, Jacob Robert F, Mason R Preston
Elucida Research, Beverly, MA 01915, USA.
Am J Cardiol. 2008 May 22;101(10A):20D-29D. doi: 10.1016/j.amjcard.2008.02.004.
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.
类胡萝卜素是天然存在的有机色素，因其抗氧化特性，被认为在治疗心血管疾病（CVD）方面具有治疗益处。然而，前瞻性随机试验未能证明类胡萝卜素β-胡萝卜素对有心血管疾病风险的患者具有一致的益处。这种明显矛盾的原因尚不清楚，但可能归因于各种类胡萝卜素因其与生物膜的结构依赖性物理化学相互作用而具有的独特抗氧化特性。为了验证这一假设，我们使用富含多不饱和脂肪酸的模型膜，测量了虾青素、玉米黄质、叶黄素、β-胡萝卜素和番茄红素对脂质过氧化的影响。使用小角X射线衍射方法确定了这些化合物对膜结构的相关影响。非极性类胡萝卜素番茄红素和β-胡萝卜素使膜双层无序化，并刺激膜脂质过氧化（脂质过氧化氢水平增加>85%），而虾青素（一种极性类胡萝卜素）保留了膜结构并表现出显著的抗氧化活性（脂质过氧化氢水平降低>40%）。这些结果表明，类胡萝卜素的抗氧化潜力取决于它们与膜脂质的独特相互作用。这种结构与功能的关系可能解释了各种类胡萝卜素所报道的生物活性差异，具有重要的治疗意义。
