Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells (Pharmacology)
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概要
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Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10-100 μM and 0.1-1 μM, respectively. While edaravone possessed no antiproliferative effect by itself at 100μM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 μM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10-100μM, 1-10 μM and 0.1-1 μM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.
- 2003-12-01
著者
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UCHIDA Masaatsu
Department of Pharmacology, Meiji Pharmaceutical University
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Uchida Masaki
Faculty Of Pharmaceutical Sciences Josai University
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Oishi K
Department Of Pharmacology Meiji Pharmaceutical University
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Oishi Kazuhiko
Department Of Pharmacology Meiji Pharmaceutical University
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Oishi Kazuhiko
Department Of Molecular Pharmacology Meiji College Of Pharmacy
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Echizen Hirotoshi
Department of Pharmacotherapy, Meiji Pharmaceutical University
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Uchida Masaatsu
Department Of Molecular Pharmacology Meiji College Of Pharmacy
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Uchida Masaatsu
Departments Of Pharmacology Meiji Pharmaceutical University
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Uchida Mihoko
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Hoshi University
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Uchida M
Otsuka Pharmaceutical Co. Ltd. Tokushima Jpn
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YAMAGUCHI Tomoaki
Departments of Hospital Pharmacy, Nakano General Hospital
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Echizen Hirotoshi
Department Of Pharmacotherapy Meiji College Of Pharmacy
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Yamaguchi Tomoaki
Departments Of Hospital Pharmacy Nakano General Hospital
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UCHIDA Masaatsu
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
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