[Effect of mevinolin and glycyrrhizinic acid on cholesterol and bile acid metabolism in cultured rabbit hepatocytes].
A comparison of effects of two hypocholesterolemic drugs--mevinolin and glycyrrhizinic acid, on cholesterol and bile acid metabolism in cultured rabbit hepatocytes has been carried out. The following parameters have been determined: i) cholesterol synthesis from [2-14C]acetate; ii) bile acid production from newly synthesized and [4-14C]-labeled HDL2 cholesterol, and, iii) total cholesterol efflux into the incubation medium Mevinolin (0.5 microgram/ml) inhibited [2-14C] acetate incorporation into cholesterol by more than 90%. Conversely, glycyrrhizinic acid did not influence cholesterol synthesis even when used at high (100 micrograms/ml) concentrations but stimulated the conversion of endogenous (by 37%) and exogenous (by 18%) cholesterol into bile acids and increased, in addition, the proportion of bile acids in the total sterol pool released from hepatocytes into the incubation medium. At the same time, mevinolin used at 0.5 microgram/ml decreased the bile acid production by endogenous (by 27%) and exogenous (by 40%) cholesterol. The data obtained suggest that glycyrrhizinic acid exerts hypocholesterolemic action by stimulation of cholesterol conversion into bile acids without any effect on cholesterol synthesis. As for mevinolin, it has a cholesterol-suppressing effect via a mechanism of cholesterol synthesis inhibition only.
Novikov
D K
DK
Mukhamedova
N A
NA
Lakeev
Iu V
IuV
Charyev
Kh E
KhE
Repin
V S
VS
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D011817:Rabbits
D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D019695:Glycyrrhizic Acid; D002784:Cholesterol; D008148:Lovastatin; D006034:Glycyrrhetinic Acid
Vliianie mevinolina i glitsirrizinovoĭ kisloty na metabolizm kholesterina i zhelchnykh kislot v kul'tiviruemykh gepatotsitakh krolika.