Water-soluble Hexasulfobutyl[60]fullerene inhibit low-density lipoprotein oxidation in aqueous and lipophilic phases.

Water-soluble Hexasulfobutyl[60]fullerene inhibit low-density lipoprotein oxidation in aqueous and lipophilic phases.
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水溶性六磺丁基[60]富勒烯抑制水相和亲脂相中的低密度脂蛋白氧化。

DOI:
10.1111/j.1525-1373.2000.22403.x
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发表时间:
2000
期刊:
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
影响因子:
--
通讯作者:
H. Hsu
H. Hsu
中科院分区:
--
文献类型:
--
作者:
Yuan;L. Chiang;Wei;H. Hsu

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低密度脂蛋白(LDL)的氧化修饰在动脉粥样硬化的发病机制中起着关键作用。因此,增加LDL对氧化的抵抗力可能会减轻甚至预防动脉粥样硬化。六磺丁基[60]富勒烯[C60 -(CH 2CH 2CH 2CH 2-SO 3 Na)6; FC 4S]是一种新型的水溶性C60衍生物,由6个磺丁基基团共价键合在C60骨架上,是一种有效的自由基清除剂。研究了磺丁基化富勒烯衍生物(FC 4S)对LDL氧化的抗氧化作用。FC 4S被认为是有效的保护LDL对氧化诱导的铜2+或偶氮过氧自由基最初产生的水相或亲脂相,分别。氧化产物、共轭二烯和硫代巴比妥酸反应物质的水平以及LDL的相对电泳迁移率均降低。在氧化的早期阶段添加20 μ M的FC 4S使动力学滞后时间从69 +/- 11增加到14 +/- 10 min(P <0. 05),并使增殖速率从17. 1 +/-2. 6降低到6. 3 +/-1. 0 mOD/min(P < 0. 05)。005)。在繁殖期间,在所有内源性抗氧化剂完全消耗后,进一步添加FC 4S,观察到过氧化反应的持续抑制。静脉注射FC 4S(1 mg/kg/天)可有效降低高胆固醇血症家兔的动脉粥样硬化形成。数据证实了FC 4S作为一种优异的亲水性抗氧化剂在水相或亲脂相中通过清除自由基来保护动脉粥样化形成。
Oxidative modification of low-density lipoprotein (LDL) plays a pivotal role in the pathogenesis of atherosclerosis. Increasing the resistance of LDL to oxidation may therefore mitigate, or even prevent, atherosclerosis. A new water-soluble C60 derivative, hexasulfobutyl[60]fullerene [C60 - (CH2CH2CH2CH2-SO3Na)6; FC4S], consisting of 6 sulfobutyl moieties covalently bound onto the C60 cage is a potent free radical scavenger. This study explored the antioxidative effect of sulfobutylated fullerene derivatives (FC4S) on LDL oxidation. FC4S was found to be effective in protecting LDL against oxidation induced by either Cu2+ or azo peroxyl radicals generated initially in the aqueous or lipophilic phase, respectively. Levels of the oxidative products, conjugated diene and thiobarbituric acid-reactive substances, and the relative electrophoresis mobility of the LDL were decreased. The addition of 20 microM FC4S at the early stage of oxidation increased the kinetic lag time from 69 +/- 11 to 14 +/- 10 min (P < 0.05) and decreased the propagation rate from 17.1 +/- 2.6 to 6.3 +/- 1.0 mOD/min (P < 0. 005). Persistent suppression of peroxidation reaction was observed upon further addition of FC4S after full consumption of all endogenous antioxidants during the propagation period. Intravenous injection of hypercholesterolemic rabbits with FC4S (1 mg/kg/day) efficiently decreased atheroma formation. Data substantiate the use of FC4S as an excellent hydrophilic antioxidant in protecting atheroma formation, via removing free radicals, in either aqueous or lipophilic phase.
DOI: --
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