Influence of simvA glyzin on expression and inhibition of hmg-coa reductase in rats liver
Abstract
Activity, level of protein and mRNA HMG-CoA reductase were investigated in rats liver treated with simvastatin (SV), its complex compound with glycyrrhizic acid – simvaglyzin (SVG) and glycyrrhizic acid alone. Level of protein HMG-CoA reductase was reduced on 25 % in SVG group (р < 0.05) 24 hours after introduction the last dose. Level of mRNA was significantly increased in experimental group in compared to control. In vitro SVG was uncompetitive inhibitor of HMG-CoA reductase (Ki = 94 nM). SVG gain the inhibitor properties following cytochrome P450-dependent metabolism. The addition of 1mM methyrapone in incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG in concentrations of 300 nM inhibited of mevalonate synthesis rate by 39.15 ± 8.27 % and 38.85 ± 3.04 %, respectively.
About the Authors
Yu. I. Ragino
Institute of Internal and Preventive Medicine
Russian Federation
Russian Federation
630089
Boris Bogatkov str., 175/1
Novosibirsk
V. A. Vavilin
Institute of Molecular Biology and Biophysics
Russian Federation
Russian Federation
630117
Timakov str., 2
Novosibirsk
E. M. Stakhneva
Institute of Internal and Preventive Medicine
Russian Federation
Russian Federation
630089
Boris Bogatkov str., 175/1
Novosibirsk
N. F. Salakhutdinov
Novosibirsk Institute of Organic Chemistry
Russian Federation
Russian Federation
630090
Academik Lavrentjev av., 9
Novosibirsk
O. G. Safronova
Institute of Molecular Biology and Biophysics
Russian Federation
Russian Federation
630117
Timakov str., 2
Novosibirsk
A. B. Shintyapina
Institute of Molecular Biology and Biophysics
Russian Federation
Russian Federation
630117
Timakov str., 2
Novosibirsk
V. V. Lyakhovich
Institute of Molecular Biology and Biophysics
Russian Federation
Russian Federation
630117
Timakov str., 2
Novosibirsk
Yu. P. Nikitin
Institute of Internal and Preventive Medicine
Russian Federation
Russian Federation
630089
Boris Bogatkov str., 175/1
Novosibirsk
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For citations:
Ragino Yu.I., Vavilin V.A., Stakhneva E.M., Salakhutdinov N.F., Safronova O.G., Shintyapina A.B., Lyakhovich V.V., Nikitin Yu.P. Influence of simvA glyzin on expression and inhibition of hmg-coa reductase in rats liver. Ateroscleroz. 2015;11(2):14-19. (In Russ.)
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