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Effects of a "tall oil" -derived phytosterol mixture on the development of atherosclerotic lesions in apo E-deficient mice Moghadasian, Mohammed H.


Background: The effects of a phytosterol mixture (FCP-3PI) on the plasma cholesterol concentrations and development of atherogenic lesions have been evaluated in apo E-knockout (apo E-KO) mice using a number of biochemical and histological methods. In addition, the systemic effects and the tolerance to FCP-3PI have also been tested in this animal model. FCP-3PI, which is composed of S-sitosterol (69%), campesterol (15%) and sitostanol (16%), was extracted from "tall oil" soap, a by-product of the pulp and paper industry. The degree of purity of the final product was approximately 95% as assessed by gas chromatography. Objectives:The objectives of this thesis were: 1) to determine the effects of dietary supplementation with FCP-3PI on plasma lipid concentrations in apo E-KO mice; 2) to evaluate the cholesterol-lowering properties of FCP-3PI in wild-type normolipidemic mice; 3) to evaluate the effects of FCP-3PI on the quality and extent of atherosclerotic lesions in apo E-KO mice; 4) to compare and contrast cholesterol-lowering and anti-atherogenic effects of FCP-3PI to those of probucol, a well-known lipid lowering agent with antioxidant properties; 5) to test systemic effects of FCP-3PI following its parenteral administration in apo E-KO mice; and finally, to investigate the tolerance of apo E-KO mice to FCP-3PI and its safety when administered over the long-term. Results: Atherosclerosis progression experiments revealed that addition of 2% (w/w) FCP-3PI to a typical "Western" diet resulted in a significant reduction in average total plasma cholesterol concentrations in the treated animals compared to controls. This was accompanied by a significant (p

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