Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits

Abstract

BackgroundProbucol 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.MethodsNew 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.ResultsAtorvastatin 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% (p < 0.01) reduction while atorvastatin treatment led to 23% (p = 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.ConclusionsThis 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.

Rabbit models for the study of human atherosclerosis: From pathophysiological mechanisms to translational medicine

“…To avoid these problems, it is sometimes better to perform pre-screening for a week to exclude those non-responder rabbits when using this model for drug development studies. To do so, all rabbits are fed a 0.5% cholesterol diet for a week and their plasma cholesterol levels are measured (Chen, et al, 2013; Niimi, et al, 2013). In this way, one can exclude those hypo-responder rabbits before the experiment.…”

Role of Oxidized LDL in Atherosclerosis

“…On the other hand, the existence of several structurally unrelated compounds such as probucol and vit E that inhibit atherosclerosis in animals, prevent the initiation of the disease due to a reduction of the oxidization of LDL [21]. In relationship to probucol, It seems to be a more effective protection against lesion formation on an early-stage of the disease than the statin-mediated lipidlowering effects [22].…”

Atorvastatin combined with poly-unsaturated fatty acid confers better improvement of dyslipidemia and endothelium function

“…Totally 50 male New Zealand White rabbits, weighing 1.2-1.5 kilogram and with 6–8 weeks old, were obtained from Experimental Animal Center of Shantou University, and the protocol of current study was approved by Ethic Committee of Shantou University. Briefly, 10 rabbits were served as the sham group, and another 40 rabbits were used as dyslipidemia group, which were prescribed with atherogenic diet containing 0.5% cholesterol for 1 week as described by previous study [ 10 ].…”