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  • Title: Some comparative effects of gemfibrozil, clofibrate, bezafibrate, cholestyramine and compactin on sterol metabolism in rats.
    Author: Maxwell RE, Nawrocki JW, Uhlendorf PD.
    Journal: Atherosclerosis; 1983 Sep; 48(3):195-203. PubMed ID: 6579963.
    Abstract:
    Liver cholesterogenesis in rats was measured by giving [l-14C]octanoate i.p.; 1 h later digitonin-precipitable sterols were isolated and counted. In rats fed normal chow and given 7 daily p.o. doses of compounds and then fasted, at 20 h after the last dose, clofibrate or bezafibrate had no effect at lower doses or inhibited incorporation at higher doses, while compactin or gemfibrozil caused increases; cholestyramine added to the diet also caused marked increases. When rats were fed chow containing 0.1% cholesterol and 5.5% peanut oil, again at 20 h following the last of 7 daily doses, gemfibrozil caused increases of incorporation which diminished at higher levels of dosage, while clofibrate caused only inhibition. A single dose of gemfibrozil caused inhibition at 3 h postdose followed by increases over control at 36 and 48 h; a single dose of compactin caused inhibition at 3 h but not subsequent increase, and a single dose of clofibrate had no effect over the entire period. In rats fed chow containing 1.5% cholesterol and 5.5% peanut oil, gemfibrozil given orally or cholestyramine in the diet prevented the diet-induced decreases of plasma HDL cholesterol and increases of liver cholesterol content, while bezafibrate treatment did not have those effects. The effects of cholestyramine rapidly disappeared when it was withdrawn from the diet, while the effects of gemfibrozil persisted after dosage was stopped. These results suggest that some of the actions of gemfibrozil on rat sterol metabolism are quantitatively different from those of the other agents tested.
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