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DOI: 10.1055/s-2008-1065348
© Georg Thieme Verlag KG Stuttgart · New York
Antiatherogenic Effects of Cilostazol and Probucol Alone, and in Combination in Low Density Lipoprotein Receptor-deficient Mice Fed with a High Fat Diet
Publication History
received 28.08.2007
accepted 15.11.2007
Publication Date:
10 April 2008 (online)
![](https://www.thieme-connect.de/media/hmr/200807/lookinside/thumbnails/10.1055-s-2008-1065348-1.jpg)
Abstract
Cilostazol, an antiplatelet drug, and probucol, a cholesterol-lowering drug, are reported to ameliorate atherosclerosis in animal models. However, their combined effect on atherosclerosis is unclear. We therefore evaluated their combined effect on atherosclerotic lesions in LDL receptor-deficient mice. Male LDL receptor-deficient mice were fed a high fat diet with or without cilostazol alone, probucol alone, or with cilostazol and probucol in combination, for 8 weeks. Body weight and plasma lipid levels were measured before and during treatment. At the end of treatment, the size distribution of plasma lipoproteins was analyzed by HPLC and then plasma HDL cholesterol levels and en face aortic atherosclerotic lesion areas were measured. Probucol alone significantly decreased both total cholesterol and HDL cholesterol, while cilostazol alone did not decrease total cholesterol, but significantly increased HDL cholesterol. Both cilostazol alone and probucol alone significantly decreased atherosclerotic lesion areas, and their combined administration showed more significant decreases than when each drug was administered singly. The combination of cilostazol and probucol was more effective in preventing atherosclerotic lesion formation than the administration of each drug alone; this may provide us with a new strategy for treating atherosclerosis.
Key words
antiplatelet agent - hypocholesterolemic agent - hypercholesterolemia - atherosclerosis - disease model
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Correspondence
T. YoshikawaPhD
Free Radical Research Institute
Ostuka Pharmaceutical Co., Ltd.
463-10 Kagasuno Kawauchi-cho
771-0192 Tokushima
Japan
Phone: +81/88/665 21 26
Fax: +81/88/665 69 76
Email: t_yoshikawa@research.otsuka.co.jp