title: 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 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.
authors.affiliation: Department of Internal Medicine (Cardiology) and the Center for Condensed Matter Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Y T
authors.initials: YT
authors.lastname: Lee
authors.forename: L Y
authors.initials: LY
authors.lastname: Chiang
authors.forename: W J
authors.initials: WJ
authors.lastname: Chen
authors.forename: H C
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D001391:Azo Compounds / Q000378:metabolism; D002244:Carbon / Q000009:adverse effects / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel / Q000379:methods; D037741:Fullerenes; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D009570:Nitriles / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects*; D011817:Rabbits; D012995:Solubility; D014867:Water
chemical_list: D001391:Azo Compounds; D037741:Fullerenes; D008077:Lipoproteins, LDL; D009570:Nitriles; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D014867:Water; D002244:Carbon; C069837:fullerene C60