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Current Chemical Biology

Author(s): Irina V. Zhigacheva*, Natalya I. Krikunova and Maksud M. Rasulov

DOI: 10.2174/2212796817666221205164816

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Adaptogenic Properties of 1-(Germatran-1-il)-Oxyethylamine

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Abstract

Background: Germanium is a biologically active trace element, and it is present in almost all organs and tissues. Its biological activity was revealed in the 20th century. However, the study on the possibility of using germanium for medical purposes was first undertaken by the Japanese scientist Dr. Kazuhiko Asai in 1940. In 1965, academician M.G.Voronkov and colleagues synthesized tricyclic esters of triethanolamine germanium with the general formula XGe(OCH2CH2)3N and studied their biological activity. However, the adaptogenic properties of these compounds have not been sufficiently studied. In this regard, there is an urgent need to study the adaptogenic properties of these drugs.

Objective: As the resistance of the organism to stress factors primarily depends on energy metabolism, the aim of our work was to study the influence of stress and 1- (germatran-1-il) –oxyethylamine (GM) on the functional state of mitochondria.

Methods: The functional state of mitochondria was studied as per the rate of mitochondria respiration by the level of lipid peroxidation and fatty acid composition of mitochondrial membranes by chromatography technique.

Results: It was shown that the drug in concentrations of 10-5, 10-6, and 10-11M reduced the intensity of LPO in the membranes of "aged" mitochondria. This may serve as evidence regarding the presence of anti-stress properties in the drug. Injection of GM at a dose of 10-5 mol/kg to rats prevented the activation of LPO in the membranes of the liver mitochondria in conditions of acute hypobaric hypoxia. Restricting lipid peroxidation, GM prevented changes in the content of C18 and C22 fatty acids in mitochondrial membranes, which probably contributed to maintaining the bioenergetic characteristics of mitochondria at the control level.

Conclusion: It is assumed that the anti-stress activity of the drug is associated with its antioxidant properties and its effect on the complex I of the mitochondrial respiratory chain.

Keywords: Germatranes, adaptogens, lipid, peroxidation, fatty acids, mitochondria.

Graphical Abstract

[1]
Marczynski, B. Carcinogenesis as the result of the deficiency of some essential trace elements. Med. Hypotheses, 1988, 26(4), 239-249.
[http://dx.doi.org/10.1016/0306-9877(88)90127-2] [PMID: 3050386]
[2]
Ishiwara, F. Reports on the entire physiology and experimental pharmacology., 1928, 49, 615.
[3]
Kaars Sijpesteijn, A.; Rijkens, F.; Kerk, G.J.M.V.D.; Manten, A. Antimicrobial activity of organogermanium derivatives. Nature, 1964, 201(4920), 736-737.
[http://dx.doi.org/10.1038/201736a0] [PMID: 14134741]
[4]
Menchikov, L.G.; Ignatenko, M.A. Biological activity of organic compounds of germanium. Pharm. Chem. J., 2012, 46(11), 3-6.
[5]
Nakamura, T.; Takeda, T.; Tokuji, Y. The oral intake of organic germanium, ge-132, elevates α-tocopherol levels in the plasma and modulates hepatic gene expression profiles to promote immune activationin mice. Int. J. Vitam. Nutr. Res., 2014, 84(3-4), 0183-0195.
[http://dx.doi.org/10.1024/0300-9831/a000205] [PMID: 26098482]
[6]
Wada, T.; Hanyu, T.; Nozaki, K.; Kataoka, K.; Kawatani, T.; Asahi, T.; Sawamura, N. Antioxidant activity of Ge-132, a synthetic organic germanium, on cultured mammalian cells. Biol. Pharm. Bull., 2018, 41(5), 749-753.
[http://dx.doi.org/10.1248/bpb.b17-00949] [PMID: 29503400]
[7]
Yablonskaya, O.V. Germatranol as an immune-stimulant in calf rearing. Bulletin of the State Agroecological University, Zhytomyr, 2002, 1, 56-62.
[8]
Spasenkov, A.I. Protein synthesis capacity and stability of two strains of tissue culture Polyscias filicifolia under stress. Abstract. PhD. Biol., St. Petersburg, 2006, 24.
[9]
Rasulov, R.M.; Gukasov, V.M.; Myakinkova, L.L; Snisarenko, T.A.; Golovanov, S.A.; Rasulov, M.M. 1-Germatranol-hydrate -activator of tryp-tophanyl-tRNA-synthetase. ; News of Higher educational establishment. Applied chemistry and biotechnology, 2018, 8(1), 153-159.
[10]
Shigarova, A.M.; Borovsky, G.B.; Zang, Th.; Nyat, Le; Bartyshok, V.P. All-Russian Scientific Conference; , 2013. June 10-13;;
Irkutsk; Voynikov, V.K.; Mi-khailova, TA; Makarova, L.E.; Antonov, I.A.; Oskolkov, V.A.; Shamanova, S.I, Eds.; Siberian institute of plant physiology and biochemistry SB RAS: Irkutsk, Russia, 2013, pp. 294-297.
[11]
Shakirova, F.M. Nonspecific plant resistance to stress factors and its regulation; Publishing house "Gilem": Ufa, 2001, p. 326.
[12]
Zorov, D.B.; Isaev, N.K.; Plotnikov, E.Y.; Zorova, L.D.; Stelmashook, E.V.; Vasileva, A.K.; Arkhangelskaya, A.A.; Khrjapenkova, T.G. The mitochondrion as janus bifrons. Biochemistry (Mosc.), 2007, 72(10), 1115-1126.
[http://dx.doi.org/10.1134/S0006297907100094] [PMID: 18021069]
[13]
Plotnikov, E.; Chupyrkina, A.; Vasileva, A.; Kazachenko, A.; Zorov, D. The role of reactive oxygen and nitrogen species in the pathogenesis of acute renal failure. BBA, 1777, 2008, S58-S59.
[14]
Todorov, I.N. Mitochondria: oxidative stress and mito-chondrial DNA mutations in the develop-ment of pathologies, the aging process, and apoptosis. Russian Chemical Journal (Journal of D.I. Mendeleev Chemical Society), 2007, 51, 93-106.
[http://dx.doi.org/10.1155/2012/724904]
[15a]
European convention for the protection of vertebrate animals used for Experimental and other Scientific Purposes (ETS 123), Strasburg. 1986.
[15b]
Karkishchenko, N.N.; Grachev, S.V. Guidance on laboratory animals and alter-native models in biomedical research, 2nd ed.; Profile: Мoscow, 2010.
[15c]
Rasulov, M.M.; Storozhenko, P.A.; Zhigacheva, I.V. Carboxylic acids and their derivatives in biology and medicine; Palmarium Academic Publishing: reha gmbh, 66111, Saarbrucken, 2018, p. 220.
[16]
Mokhova, E.N.; Skulachev, V.P.; Zhigacheva, I.V. Activation of the external pathway of NADH oxidation in liver mitochondria of cold-adapted rats. Biochim. Biophys. Acta Bioenerg., 1978, 501(3), 415-423.
[http://dx.doi.org/10.1016/0005-2728(78)90109-3] [PMID: 204343]
[17]
Fletcher, B.L.; Dillard, C.J.; Tappel, A.L. Measurement of fluorescent lipid peroxidation products in biological systems and tissues. Anal. Biochem., 1973, 52(1), 1-9.
[http://dx.doi.org/10.1016/0003-2697(73)90327-8] [PMID: 4696687]
[18]
Carreau, J.P.; Dubacq, J.P. Adaptation of a macro-scale method to the micro-scale for fatty acid methyl transesterification of biological lipid extracts. J. Chromatogr. A, 1978, 151(3), 384-390.
[http://dx.doi.org/10.1016/S0021-9673(00)88356-9]
[19]
Wang, Y.; Sunwoo, H.; Cherian, G.; Sim, J.S. Fatty acid determination in chicken egg yolk: a comparison of different methods. Poult. Sci., 2000, 79(8), 1168-1171.
[http://dx.doi.org/10.1093/ps/79.8.1168] [PMID: 10947186]
[20]
Zhigacheva, I.; Binyukov, V.; Mil, E.; Krikunova, N.; Generozova, I.; Rasulov, M. Iron-sulfur-nitrosyl complex increases the resistance of pea seedling to water deficiency. Curr. Chem. Biol., 2020, 14(3), 203-215.
[http://dx.doi.org/10.2174/2212796814999200907162619]
[21]
Golovnya, R.V.; Kuzmenko, T.E. Thermodynamic evaluation of the interaction of fatty acid methyl esters with polar and non-polar stationary phases, based on their retention indices. Chromatographia, 1977, 10(9), 545-548.
[http://dx.doi.org/10.1007/BF02262915]
[22]
Zhigacheva, I.V.; Mil, E.M. Potassium phenosan as an adaptogen to stress. WJPLS, 2016, 2(6), 556-566.
[23]
Lukyanova, L. D. Bioenergetic hypoxia: the concept, mechanisms and methods of correction. Bull. expert. biol. and med., 1997, 124(9), 244-254.
[24]
de Carvalho, C. C. C. R.; Caramujo, M. J. The various roles of fatty acids. Molecules, 2018, 23(10), E 2583.
[http://dx.doi.org/10.3390/molecules23102583]
[25]
Paradies, G.; Petrosillo, G.; Pistolese, M.; Di Venosa, N.; Federici, A.; Ruggiero, F.M. Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: involvement of reactive oxygen species and cardiolipin. Circ. Res., 2004, 94(1), 53-59.
[http://dx.doi.org/10.1161/01.RES.0000109416.56608.64] [PMID: 14656928]
[26]
Acin-Perez, R.; Enriquez, J.A. The function of the respiratory supercomplexes: The plasticity model. Biochim. Biophys. Acta Bioenerg., 2014, 1837(4), 444-450.
[http://dx.doi.org/10.1016/j.bbabio.2013.12.009] [PMID: 24368156]
[27]
Zhigacheva, I.; Burlakova, E.B.; Generozova, I.P.; Shugaev, A.G. Role of adaptogens in regulation of bioenergetic mitochondrial function under stress. Biochemistry (Moscow). Supplement Series A: Membrane and Cell Biologyю, 2013, 30(4), 313-321.
[http://dx.doi.org/10.7868/S0233475513040105]
[28]
Studentsov, Y.P.; Ramsh, S.M.; Kazurova, N.G.; Neporozhneva, O.V.; Garabadzhiu, A.V.; Kochina, T.A.; Voronkov, M.G.; Kuznetsov, V.A.; Krivorotov, D.V. Adaptogens and related groups of drugs - 50 years of research. Reviews on Clinical Pharmacology and Drug Therapy, 2013, 11(4), 3-43.
[http://dx.doi.org/10.17816/RCF1143-43]
[29]
Rasulov, R.M.; Gukasov, V.M.; Myakinkova, L.L.; Snisarenko, T.A.; Golovanov, S.A.; Rasulov, M.M. Modern ideas about the possibilities of using adaptogens. Innovatics and Expert Examination, 2020, 1(1(29)), 77-89.
[http://dx.doi.org/10.35264/1996-2274-2020-1-77-89]
[30]
Zhigacheva, I.V.; Burlakova, E.B. Adaptogens decrease the generation of reactive oxygen species by mitochondria. In: Research progress in chemical and biochemical physics. Pure and applied science; Nova publishers: New-York, 2014; pp. 193-205.
[31]
Oemer, G.; Lackner, K.; Muigg, K.; Krumschnabel, G.; Watschinger, K.; Sailer, S.; Lindner, H.; Gnaiger, E.; Wortmann, S.B.; Werner, E.R.; Zschocke, J.; Keller, M.A. Molecular structural diversity of mitochondrial cardiolipins. Proc. Natl. Acad. Sci. USA, 2018, 115(16), 4158-4163.
[http://dx.doi.org/10.1073/pnas.1719407115] [PMID: 29618609]
[32]
Paradies, G.; Paradies, V.; Ruggiero, F.M.; Petrosillo, G. Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects. Cells, 2019, 8(7), 728-749.
[http://dx.doi.org/10.3390/cells8070728] [PMID: 31315173]