文章基本信息

标题：Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells
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作者：Tomoaki Yamaguchi ; Kazuhiko Oishi ; Masaatsu Uchida 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2003
卷号：26
期号：12
页码：1706-1710
DOI：10.1248/bpb.26.1706
出版社：The Pharmaceutical Society of Japan
摘要：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 μ M and 0.1—1 μ M , respectively. While edaravone possessed no antiproliferative effect by itself at 100 μ M , 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 μ M with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10—100 μ M , 1—10 μ M and 0.1—1 μ M , 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.
关键词：edaravone;free radical;basilar artery smooth muscle cell;atherosclerosis;amlodipine;fluvastatin