Probucol, but not MaxEPA fish oil, inhibits mononuclear cell adhesion to the aortic intima in the rat model of atherosclerosis

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Abstract
We have examined the influence of both dietary fish oil and probucol on monocyte adhesion to the aortic endothelium of rats fed an atherogenic diet for 2 weeks. All rats were fed a low-fat diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil. In addition to the atherogenic diet, group 1 (FO; n = 20) received a dietary supplement of the fish oil concentrate MaxEPA (5% w/w); group 2 (CO; n = 20) received a supplement of a control oil with the same polyunsaturated–monounsaturated–saturated fatty acid ratio as MaxEPA; and group 3 (PR; n = 20) received both the control oil supplement (5% w/w) and a 1% (w/w) supplement of probucol. Analysis of blood samples taken at 2 weeks revealed that both fish oil and probucol lowered total plasma cholesterol by 30% compared with the CO group. In addition, fish oil supplementation caused a significant decrease in cholesterol contained in the VLDL fraction while probucol supplementation significantly lowered cholesterol in the HDL fraction. Analysis of mononuclear cell adhesion to the aortic endothelium in vivo revealed that, while fish oil had no significant effect, probucol reduced adhesion by 40%. The results of this study suggest that probucol, but not fish oil, may inhibit the initiation of lesion formation in the rat model of atherosclerosis.Key words: rat, hypercholesterolemia, monocyte adhesion, fish oil, probucol.