Probucol attenuates the development of aortic atherosclerosis in cholesterol‐fed rabbits

1 Probucol was administered to rabbits fed a cholesterol‐enriched (2% wt/wt) diet to determine potential anti‐atherogenic effects in a preparation in which the disease process is due to elevated plasma concentrations of cholesterol ester‐rich very low density lipoproteins (CER‐VLDL). 2 Probucol was supplemented to the diet at 1% wt/wt which resulted in plasma concentrations rising steadily to 53 ± 8 μg ml−1 after 14 days, with no significant changes during continued administration. Dietary consumption and body weight gains were comparable in the drug‐treated and control groups during the observation period. 3 Probucol treatment did not significantly affect plasma concentrations of total cholesterol, unesterified cholesterol, triglycerides or phospholipids. 4 The concentration of CER‐VLDL in plasma and its physicochemical characteristics were not significantly changed during administration of probucol. CER‐VLDL from both control and probucol‐treated animals was a potent stimulant of the augmentation of the intracellular incorporation of [3H]‐oleate into cholesteryl‐[3H]‐oleate in cultured macrophages. 5 Despite the lack of effect of probucol on concentrations of plasma lipids and the cell interaction characteristics of CER‐VLDL, administration of the drug markedly decreased the extent of intimal aortic surface area covered by grossly discernible atherosclerotic lesions from 55.6 ± 11.8% to 11.6 ± 1.9% in thoracic sections, and from 49.1 ± 10.2% to 7.2 ± 0.4% in abdominal sections. Furthermore, probucol treatment significantly reduced the deposition of total cholesterol in vascular tissue. 6 Probucol reduced the extent of aortic atherosclerosis produced by diet‐induced hypercholesterolemia in rabbits. This reduction occurred in the absence of any significant change in the characteristics of plasma lipoproteins that were determined. These results indicate that either there is a role of oxidation in the disease process of this animal model of atherosclerosis or that probucol is acting via a presently undefined mechanism.