Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells
Tomoaki YamaguchiKazuhiko OishiMasaatsu UchidaHirotoshi Echizen
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2003 Volume 26 Issue 12 Pages 1706-1710

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Abstract

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 100 μM, 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—100 μM, 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.

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© 2003 The Pharmaceutical Society of Japan
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