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

Oxidative modification of low-density lipoprotein (LDL) plays a pivotal rol e in the pathogenesis of atherosclerosis. Increasing the resistance of LDL to oxidation may therefore mitigate, or even prevent, atherosclerosis. A ne w water-soluble C-60 derivative, hexasulfobutyl[60]fullerene [C-60 - (CH2CH 2CH2CH2-SO3Na)(6); FC4S], consisting of 6 sulfobutyl moieties covalently bo und onto the C-60 cage is a potent free radical scavenger. This study explo red 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 initial ly in the aqueous or lipophilic phase, respectively. Levels of the oxidativ e products, conjugated diene and thiobarbituric acid-reactive substances, a nd the relative electrophoresis mobility of the LDL were decreased. The add ition of 20 mu M 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 prop agation rate from 17.1 +/- 2.6 to 6.3 +/- 1.0 mOD/min (P < 0.005). Persiste nt suppression of peroxidation reaction was observed upon further addition of FC4S after full consumption of all endogenous antioxidants during the pr opagation period. Intravenous injection of hypercholesterolemic rabbits wit h FC4S (1 mg/kg/day) efficiently decreased atheroma formation. Data substan tiate the use of FC4S as an excellent hydrophilic antioxidant in protecting atheroma formation, via removing free radicals, in either aqueous or lipop hilic phase.