Abstract
5 alpha-Cholest-8(14)-en-3 beta-ol-15-one has been found to have significant hypocholesterolemic activity upon oral administration at a daily dosage of 75 mg/kg of body weight to Rhesus monkeys fed a diet of moderate cholesterol (Chol) content [0.19 mg/kcal (1 cal = 4.184 J) of diet]. The reductions in total serum Chol levels (mean, -41%) were associated with even more striking reductions (mean, -61%) in the levels of low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) Chol and also with increases in high density lipoprotein (HDL) Chol levels (mean, +61%). The mean increase in HDL Chol was 33 mg/dl. In one animal, that with the lowest pretreatment HDL Chol level, the extent of the rise was 49 mg/dl (+120%). These changes were associated with reductions in the % of total serum Chol associated with LDL/VLDL, in the ratios of total Chol to HDL Chol and of LDL/VLDL Chol to HDL Chol, and in the levels of LDL protein. The 15-ketosterol also increased the % of total Chol associated with HDL, increased the level of HDL protein, and induced a shift in the HDL profile to one in which the HDL2 species was the predominant species. All of these changes are those generally considered desirable for the treatment and/or prevention of atherosclerosis.
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