Water‐Soluble Hexasulfobutyl[60]fullerene Inhibit Low‐Density Lipoprotein Oxidation in Aqueous and Lipophilic Phases

Abstract. 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 C 60 derivative, hexasulfobutyl[60]fullerene [C 60 − (CH 2 CH 2 CH 2 CH 2 ‐SO 3 Na) 6 ; FC 4 S], consisting of 6 sulfobutyl moieties covalently bound onto the C 60 cage is a potent free radical scavenger. This study explored the antioxidative effect of sulfobutylated fullerene derivatives (FC 4 S) on LDL oxidation. FC 4 S was found to be effective in protecting LDL against oxidation induced by either Cu 2+ 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 μ M FC 4 S 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 FC 4 S after full consumption of all endogenous antioxidants during the propagation period. Intravenous injection of hypercholesterolemic rabbits with FC 4 S (1 mg/kg/day) efficiently decreased atheroma formation. Data substantiate the use of FC 4 S as an excellent hydrophilic antioxidant in protecting atheroma formation, via removing free radicals, in either aqueous or lipophilic phase.