Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice : Possible mechanisms of action

• Published in: Circulation (New York, N.Y.) N.Y.), 1999-04, Vol.99 (13), p.1733-1739
• Main Authors: MOGHADASIAN, M. H, MCMANUS, B. M, GODIN, D. V, RODRIGUES, B, FROHLICH, J. J
• Format: Article
• Language: English
• Subjects: Animals; Anticholesteremic Agents - pharmacology; Antioxidants - metabolism; Aorta, Thoracic - drug effects; Aorta, Thoracic - enzymology; Aorta, Thoracic - pathology; Apolipoproteins E - deficiency; Arteriosclerosis - etiology; Arteriosclerosis - genetics; Arteriosclerosis - pathology; Arteriosclerosis - prevention & control; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Enzyme Activation - drug effects; Fibrinogen - analysis; Glutathione Peroxidase - blood; Glutathione Reductase - blood; Lipase - blood; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols - pharmacology; Probucol - blood; Probucol - pharmacology; Superoxide Dismutase - blood
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.99.13.1733

The effects of probucol and a phytosterol mixture (FCP-3PI) on atherosclerotic lesion formation, plasma lipoproteins, hepatic and lipoprotein lipase activities, antioxidant enzyme activities, and plasma fibrinogen were investigated in apolipoprotein E-knockout (apoE-KO) mice. Three groups of 8 mice were fed a diet containing 9% (wt/wt) fat (controls) or the foregoing diet supplemented with either 1% (wt/wt) probucol (the probucol group) or 2% (wt/wt) FCP-3PI (the FCP-3PI group) for 20 weeks. Compared with controls, atherosclerotic lesion size was 3 times greater in the probucol group, whereas it was decreased by half in the FCP-3PI group. Probucol treatment resulted in high plasma probucol concentrations, which correlated (r=0.69) with the lesion area. HDL cholesterol was reduced (>75%) in the probucol group and slightly increased (14%) in the FCP-3PI-treated group. Postheparin lipoprotein lipase (LPL) activity was significantly reduced in both treatment groups, but only FCP-3PI significantly decreased hepatic lipase activity. Plasma fibrinogen was increased 42% by probucol and decreased 19% by FCP-3PI relative to controls. Probucol significantly increased plasma glutathione reductase, glutathione peroxidase, and superoxide dismutase activities (P