Water-Soluble Hexasulfobutyl [60] Fullerene Inhibits Plasma Lipid Peroxidation by Direct Association with Lipoproteins

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Abstract
Free radicals can induce lipid peroxidation, leading to the formation of atherosclerosis. A new class of water-soluble C60 derivative, hexasulfobutyl [60] fullerene [C60-(CH2CH2CH2CH2SO3Na)6; (FC4S)], comprising six sulfobutyl functional groups covalently bound on a C60 cage, is a potent free radical scavenger. This study sought to define the effect of FC4S in protecting plasma from peroxidation. At concentrations of 10-100 μM, FC4S efficiently protected plasma against Cu2+-induced oxidation, as shown by maintenance of apoprotein B integrity and decrease in oxidative products levels, conjugated diene, and thiobarbituric acid-reactive substances. Addition of FC4S to both plasma and isolated lipoproteins, including very low density, low-density, and high-density lipoproteins, resulted in an increased mobility of the lipoprotein on agarose gel electrophoresis. This was attributed to FC4S associating with the lipoproteins because of the negative charge of the sulfonate groups after hydrolysis in the electrophoretic buffer. When lipoprotein was oxidized by 2,2-azobis (2,4-dimethyl-valeronitrile), which produces peroxyl radicals within lipoprotein, but not in the aqueous phase, the FC4S still efficiently inhibited lipoprotein oxidation. These data substantiate that FC4S acts efficiently in protecting plasma lipid from oxidation by associating with lipoprotein to scavenge free radicals in both the aqueous and lipophilic phases.

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