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Open Access Highly Accessed Research

Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits

Manabu Niimi1, Yuka Keyamura2, Masanori Nozako2, Takashi Koyama2, Masayuki Kohashi2, Reiko Yasufuku2, Tomohiro Yoshikawa2 and Jianglin Fan1*

Author Affiliations

1 Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

2 Free Radical Research Project, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan

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Lipids in Health and Disease 2013, 12:166  doi:10.1186/1476-511X-12-166

Published: 4 November 2013

Abstract

Background

Probucol and statin are often prescribed for treating atherosclerosis. These two drugs exhibit different mechanisms but it is unknown whether they have the same anti-atherogenic properties. In the current study, we examined whether these two drugs at optimal doses could inhibit the initiation of atherosclerosis in cholesterol-fed rabbits in the same way.

Methods

New Zealand White rabbits were fed a cholesterol-rich diet for 5 weeks to produce the early-stage lesions of atherosclerosis. Drug-treated rabbits were administered either probucol or atorvastatin and serum lipids and aortic atherosclerotic lesions were compared with those in a control group.

Results

Atorvastatin treatment significantly reduced serum total cholesterol levels while probucol treatment led to significant reduction of high-density lipoprotein cholesterol levels without changing total cholesterol levels compared with those in the control group. Compared with the control, probucol treatment led to 65% (pā€‰<ā€‰0.01) reduction while atorvastatin treatment led to 23% (pā€‰=ā€‰0.426) reduction of the aortic lesion area. Histological and immunohistochemical analyses revealed that the lesions of the probucol-treated group were characterized by remarkable reduction of monocyte adherence to endothelial cells and macrophage accumulation in the intima compared with those of both atorvastatin and control groups. Furthermore, low-density lipoprotein (LDL) isolated from the probucol group exhibited prominent anti-oxidative reaction, which was not present in LDL isolated from either the atorvastatin-treated or the control group.

Conclusions

This study suggests that probucol inhibits the initiation of atherosclerosis by reducing monocyte adherence and infiltration into the subintima. Anti-oxidization of LDL by probucol protects more effectively against early-stage lesion formation than statin-mediated lipid-lowering effects.

Keywords:
Atherosclerosis; Monocyte; Probucol; Atorvastatin; Hypercholesterolemia