Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences (ITEB RAS)
Murashev.A.N. - Branch of the Institute of Bioorganic chemistry of the Russian Academy of Sciences (BIBC RAS)
Brief summary
Previously it was shown that the course of the succinate-containing mixture, which consists of 50% ammonium succinate, small amounts of calcium, magnesium disuccinate, zinc difumarate, sodium L-glutamate, glycine, tocopheryl acetate, facilitates or eliminates pathological symptoms of menopausal syndrome in women during early menopause. This effect was due to the increased sensitivity to the direct and feedback regulatory signals in hypothalamus-pituitary-ovarian axis.
In this paper we attempt to experimentally determine the effect of succinate-containing drug on energy metabolism in vivo by analyzing mitochondrial activity in immobilized peripheral blood lymphocytes and on integral indicators of the hormonal status of female rats during reproductive and late post- reproductive periods. Reduction of nitroblue tetrazolium to formazan (cytobiochemiccal study of lymphocyte mitochondria) indicates that the two-week course the chosen substrate composition at a dose of 5.7 mg/kg per day induced activation of succinate dehydrogenase (SDH) and inhibition of α- ketoglutarate dehydrogenase (KDH). Simultaneously it smoothed age differences in the ratio of SDH and KDH activities: in old animals the ratio of SDH/KDH increased from 1.5 to 7 - the value which is inherent to the reproductive female rats. In the presence of malonate (SDH inhibitor) had a high level of free-radical reduction of nitroblue tetrazolium in old rat mitochondria, but formazan level fell to zero after a course of succinate -containing drug. Contrary to expectations, succinate in used composition did not raise blood pressure in animals, but had a pronounced effect on the hormonal status: increased duration of the phases of proestrus and estrus in estrous cycle, along with a sharp shortening of diestrus phase initially elongated in old rats. The observed effects might be assessed as \\\\\\\"anti-aging\\\\\\\" with simpathotonic activation of the neuroendocrine system.
4. Dilman V.M., Anisimov V.N., Kondrashova M.N. Vliyanie yantarnoi i glytaminovoi kislot na chyvstvitelnost gipotalamo-gonadotropnoi sistemi k ingibiryushemy deistviu estrogenov y starih kris.//Farmakologiya toksikologiya. 1976. 3, 540-549.
6. He W., Mlao F., Lin D., Schwandner R.T., Wang Z., Gao J., Chen J.-L., Tlan H., Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors.// Nature. 2004. 429, 188–193.
7. Maevsky E.I., Rosenfeld A.S.,.Grishina E.V, Peskov A.B., Kondrashova M.N. Signal , Sympathetic action of succinate in experimental and clinical studies. //BBA. Bioenergetics. 14th EBEC Short Reports. ed. V.Borisov. 2006. Supplement v. 14 (2): 536-537.
8. Bentov Y, Esfandiari N, Burstein E, et al. The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients.//Fertility and Sterility. 2010. 93 (1): 272–275.
9. Maevskii E.I., Ychitel M.L. Sredstvo i nabor dlya normalizacii fynkcionalnih naryshenii, voznikaushih v predklimaktericheskii i klimaktericheskii period. / Patent RF № 2220712..10.01.2004.
10. Maevsky E.I., Peskov A.B., Uchitel M.L., Pogorelov A.G., Saharova N.Y., Vihlyantseva E.F., Bogdanova L.A., Kondrashova M.N. A succinate–based composition reverses menopausal symptoms without sex hormone replacement therapy (ryssk. i angl. versii) //Yspehi gerontologii.-Adv. gerentol. 2008. 21(2): 298-305.
12. Vargas S.L., Toma I., King J.J., Meer E.J., Peti-Peterdi J. Activation of the Succinate Receptor GPR91 in Macula Densa Cells Causes Renin Release //J. Am. Soc. Nephrol. 2009: 20(5). p.1002-1011.
13. Dröse S., Bleier L., Brandt U. A Common Mechanism Links Differently Acting Complex II Inhibitors to Cardioprotection: Modulation of Mitochondrial Reactive Oxygen Species Production // Molecular Pharmacology May. 2011 v. 79.(5) 814-822.
14. Marcondes, F. K.; Bianchi, F. J. and Tanno, A. P.. Determination of the estrous cycle phases of rats: some helpful considerations. //Braz. J. Biol. 2002. 62(4A): 609-614.
15. Zakharchenko M,V., Zakharchenko A.V., Khunderyakova N.V., Tutukina M.N., Simonova M.A., Vasilieva A.A., Romanova O.I., Fedotcheva N.I., Litvinova E.G., Maevsky E.I., Zinchenko V.P., Berezhnov A.V., Morgunov I.G., Gulayev A.A., Kondrashova M.N. // Burst of succinate dehydrogenase and α-ketoglutarate dehydrogenase activity in concert with the expression of genes coding for respiratory chain proteins underlies short-term beneficial physiological stress in mitochondria.// Int J Biochem Cell Biol. 2013;45(1):190-200.