[The effect of probucol and its new analog on cholesterol and lipoprotein metabolism in rabbit cultured hepatocytes].
The effects of the well-known hypolipidemic drug probucol and its new analog K5 on cholesterol and bile acid metabolism in cultured rabbit hepatocytes have been studied. Probucol (100 microM) inhibited by 24-28% the [2-14C]acetate incorporation into cholesterol. In contrast, the probucol analog K5 used at the same concentration did not affect the cholesterol synthesis but reduced by 44-55% the VLDL-apolipoprotein B (apo-B) secretion into the culture medium. Neither of the drugs influenced the [14C]leucine incorporation into cellular proteins. In addition, probucol (100 microM) stimulated by 29-64% the specific uptake of 125I-labelled LDL into the cells and increased the glycocholic and taurocholic acid synthesis by 29-93% and 45-77%, respectively, the total bile acid synthesis from [4-14C]cholesterol synthesis being increased by 25-36%. K5 had no appreciable effect on this process. The data obtained suggest that the enhanced specific uptake of LDL into hepatocytes as well as the slight inhibition of cholesterol synthesis and stimulation of cholesterol conversion into bile acids can, at least partly, account for the hypolipodemic effect of probucol. The observed reduction in the secretion of the hepatocyte apo-B containing lipoprotein by the probucol analog K5 suggests it to be a potentially hypolipodemic compound.
Mambetisaeva
E T
ET
Kosenkov
E I
EI
Podrez
E A
EA
Samuilov
Ia D
IaD
Kosykh
V A
VA
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011341:Probucol / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits
D001647:Bile Acids and Salts; D008074:Lipoproteins; D002784:Cholesterol; D011341:Probucol
Vliianie probukola i ego novogo analoga na metabolizm kholesterina i lipoproteidov v kul'tiviruemykh gepatotsitakh krolika.