INFLUENCE OF simvaglyzin ON expression AND INHIBITION of HMG-CoA reductase in rats liver
Yu.I. Ragino1, V.A. Vavilin2, E.M. Stakhneva1, N.F. Salakhutdinov3, O.G. Safronova2, A.B. Shintyapina2, V.V. Lyakhovich2, Yu.P. Nikitin1
1Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Institute of Molecular Biology and Biophysics, 630117, Novosibirsk, Timakov str., 2
3Novosibirsk Institute of Organic Chemistry, 630090, Novosibirsk, Academik Lavrentjev av., 9
Keywords: glycyrrhizic acid, simvastatin, complex compound simvaglyzin, HMG-CoA reductase
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.
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