The effect of khellin and timefurone on secretion and catabolism of lipoproteins by cultured human and rabbit hepatocytes

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.