[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.
Volgushev
S A
SA
Kosykh
V A
VA
Podrez
E A
EA
Novikov
D K
DK
Fuki
I V
IV
Karpov
R S
RS
Repin
V S
VS
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007666:Khellin / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001578:Benzopyrans; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C046829:timefurone; D007666:Khellin
Vliianie kellina i taĭmfurona na sekretsiiu i katabolizm lipoproteidov kul'tiviruemymi gepatotsitami cheloveka i krolika.