The effect of khellin and timefurone on secretion and catabolism of lipoproteins by cultured human and rabbit hepatocytes
1990
: Using human and rabbit hepatocyte cultures, the effects of khellin and timefurone on lipoprotein metabolism were studied with special reference to the following parameters: i) binding and degradation of 125I-labeled low density lipoproteins (LDL); ii) apoprotein B (apo-B) secretion measured by immunoenzymatic assay, iii) [35S]methionine labeled apo-B and apo-E within the composition of very low density lipoproteins (VLDL); iiii) total cholesterol synthesis and cholesterol secretion within the composition of VLDL. The therapeutic concentrations (0.1-10 micrograms/ml) of the above drugs had no appreciable effect on the binding and degradation of 125I-LDL but inhibited the secretion of apo-B VLDL, leaving the apo-E VLDL unaffected. This was paralleled with inhibition of cholesterol synthesis (by 30-50%) and VLDL secretion. These results suggest that khellin and timefurone mediate the hypolipidemic effect via the reduction of the intracellular synthesis of cholesterol and secretion of apo-B containing VLDL by hepatocytes.
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