title: Antioxidative effects of fluvastatin on superoxide anion activated by angiotensin II in human aortic smooth muscle cells.
abstract: We examined the antioxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), on superoxide anion formation activated by angiotensin II (Ang II) in vitro. The effects of fluvastatin were also compared to simvastatin and a water-soluble analog of alpha-tocopherol, trolox. Treatment of human aortic smooth muscle cells (hASMC) with Ang II for 24 hours resulted in a 3.2 +/- 0.5-fold increase in intracellular superoxide anion formation as detected by lucigenin assay. hASMC treated with clinical concentrations of fluvastatin (0-100 nM) showed a dose-dependent decrease in Ang II-activated superoxide anion formation. The addition of similar concentrations of trolox to hASMC inhibited Ang II-activated superoxide anion formation in a dose-dependent manner. However, simvastatin at similar doses failed to inhibit Ang II-activated superoxide anion formation by hASMC. Our results indicate that in addition to its hypocholesterolemic effect, fluvastatin may have direct antioxidative effects, suggesting its possible protective effect on atherosclerotic process.
authors.affiliation: Department of Health and Social Welfare, Fukuoka College of Health Sciences, 2-15-1 Tamura, Sawara-Ku 814-0193, Japan. mkuki@minf.med.fukuoka-u.ac.jp
authors.forename: Mari
authors.initials: M
authors.lastname: Kugi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Junko
authors.initials: J
authors.lastname: Ono
authors.forename: Kikuo
authors.initials: K
authors.lastname: Arakawa
authors.forename: Jun
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013481:Superoxides; D000804:Angiotensin II; D000077340:Fluvastatin; D019821:Simvastatin