Antioxidative effects of fluvastatin on superoxide anion activated by angiotensin II in human aortic smooth muscle cells.
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.
Kugi
Mari
M
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
Matsunaga
Akira
A
Ono
Junko
J
Arakawa
Kikuo
K
Sasaki
Jun
J
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*
D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013481:Superoxides; D000804:Angiotensin II; D000077340:Fluvastatin; D019821:Simvastatin