Assessing Lipid Lowering and Plasma Cholesteryl Ester Transfer Protein Activity of Simvastatin Following Administration to Rabbits Fed a High Fat/Cholesterol Diet

ABSTRACT

Purpose: The purpose of this study was to assess the lipid lowering and plasma cholesteryl ester transfer protein (CETP) activity following administration of simvastatin to rabbits fed a high fat/cholesterol diet. Methods: Male New Zealand white rabbits were housed in individual cages and fed a standard diet for 7 days. After 7 days, animals were fed 10 g of a regular chow diet plus 100 g of the same diet supplemented with 0.5% (w/v) cholesterol and 14.0% (w/v) coconut oil for 28 days. Following 28 days on this diet, the animals were randomized based on plasma cholesterol and triglyceride levels, into a group of control animals and a group (n = 6) of animals fed 100 g of cholesterol/coconut diet plus 10 g regular chow diet containing simvastatin (3 mg/kg/day) for an additional 28 days. Blood samples were taken from the marginal ear vein prior to and 28 days after the initiation of drug treatment. Plasma was harvested and stored at 4°C prior to lipid analysis. Plasma total cholesterol and triglyceride levels were quantified using enzymatic kits. HDL (high-density lipoproteins) cholesterol levels were determined using the dextran sulfate-Mg²⁺ precipitation method. ApoB cholesterol levels were determined by subtracting total cholesterol from HDL cholesterol. Cholesteryl ester transfer protein (CETP) activity was determined by standard assay methods. Results: We observed that simvastatin significantly reduced total plasma cholesterol, triglyceride, and apoB cholesterol compared to non-treated controls. Simvastatin treatment did not alter serum CETP activity compared to non-treated controls. Conclusions: These findings suggest that decreasing plasma lipid levels by treatment with simvastatin is not due to changes in serum CETP activity in rabbits fed a high fat/cholesterol diet.