Actoprotective Activity of Dimethylaminoethanol Compounds Combined with Intermediates of the Citric Acid Cycle
https://doi.org/10.33647/2074-5982-17-2-58-70
Abstract
The article presents the results of evaluation of actoprotective activity of combined dimethylaminoethanol compounds containing intermediates of the citric acid cycle (L-malate, α-ketoglutarate, succinate and fumarate). The effect of long-term intragastric administration of pharmacological agents for 4 weeks at a dose of 75 mg/kg on the static, dynamic endurance, motor coordination and body weight gain of “trained” laboratory animals was assessed in comparison with reference actoprotector ethylthiobenzimidazole (25 mg/kg, intragastrically). It was found that the most promising substances for further study are alpha-ketoglutarate and succinate compounds. After 1 month of training, dynamic endurance and coordination of movements were most infl uenced by DMAE-malate (increase by 60%, p=0.011), static endurance was increased during the 2nd week by DMAE-malate (by 16%, p=0.005) and DMAE-ketoglutarate (by 15.8%, p=0.006), on the 4th week – DMAE-ketoglutarate (by 19.7%, p=0.0001) and DMAE-succinate (by 12.2%, p=0.003). A pronounced body weight increase was observed in the group receiving DMAE-ketoglutarate (by 29%, p=0.022). In general, combined compounds of dimethylaminoethanol with alpha-ketoglutarate, malate and succinate showed the highest actoprotective activity.
About the Authors
E. Yu. Chistyakova
Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health care of Russia
Russian Federation
Russian Federation
Elizaveta Yu. Chistyakova
197376, Saint Petersburg, Professora Popova Str., 14A
S. V. Okovitiy
Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health care of Russia
Russian Federation
Russian Federation
Sergey V. Okovitiy, Dr. Sci. (Med.), Prof.
197376, Saint Petersburg, Professora Popova Str., 14A
V. N. Yuskovec
Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health care of Russia
Russian Federation
Russian Federation
Valerii N. Yuskovec, Cand. Sci. (Chem.)
197376, Saint Petersburg, Professora Popova Str., 14A
D. S. Lisitskii
Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health care of Russia
Russian Federation
Russian Federation
Dmitrii S. Lisitskii, Cand. Sci. (Biol.)
197376, Saint Petersburg, Professora Popova Str., 14A
A. B. Verveda
Scientific and Clinical Center of Toxicology named after Academician S.N. Golikov of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Alexey B. Verveda, Cand. Sci. (Med.)
192019, Russian Federation, Saint Petersburg, Bekhtereva Str., 1
References
1. Karkischenko V.N., Fokin Yu.V., Kazakova L.Kh., Alimkina O.V., Kasinskaya N.V. Metodiki izuchenija fi ziologicheskih funkcij laboratornyh zhivotnyh dlja doklinicheskih issledovanij v sportivnoj medicine [Methods for studying the physiological functions of laboratory animals for preclinical research in sports medicine]. Biomedicina [Journal Biomed]. 2012;4:15–21. (In Russian)].
2. Karkischenko N.N., Ujba V.V. Ocherki sportivnoj farmakologii. T. 4. Vektory jenergoobespechenija [Essays on sports pharmacology. Vol. 4. Vectors of energy supply]. Moscow, Saint Petersburg: Ajsing Publ., 2014:296. (In Russian)].
3. Klochkov A.V., Baranov L.G. Razvitie vynoslivosti [Development of endurance]: Guidelines. Mogilev: MGU imeni A.A. Kuleshova Publ., 2017:30. (In Russian)].
4. Maevskij E.I., Grishina E.V. Biohimicheskie osnovy mehanizma dejstvija fumarat-soderzhashhih preparatov [Biochemical basis of the mechanism of action of fumarate-containing preparations]. Biomedical Journal Medline.ru. 2017;18:50– 80. (In Russian)].
5. Metodicheskie rekomendacii FMBA Rossii. Biomedicinskoe (doklinicheskoe) izuchenie lekarstvennyh sredstv, vlijajushhih na fi zicheskuju rabotosposobnost’ [Methodical recommendations of FMBA of Russia. Biomedical (preclinical) study of drugs that affect physical performance]. Moscow, 2017:134. (In Russian)].
6. Okovityj S.V., Rad’ko S.V. Vlijanie razlichnyh farmakologicheskih veshhestv na vosstanovlenie fi zicheskoj rabotosposobnosti posle nagruzok v jeksperimente [The infl uence of various pharmacological substances on the restoration of physical performance after exercise in the experiment]. Experimental and Clinical Pharmacology. 2018;4:28–32. (In Russian)].
7. Okovityj S.V., Rad’ko S.V. Primenenie sukcinatov v sporte [The use of succinates in sports]. Voprosy kurortologii, fi zioterapii i lechebnoj fi zicheskoj kul’tury [Questions of balneology, physiotherapy and physical therapy]. 2015;92(6):59–65. (In Russian)].
8. Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. Chast’ pervaja [Guidelines for conducting preclinical studies of drugs. Part one]. Ed. by A.N. Mironov. Moscow: Izdvo Grif i K. 2012:944. (In Russian)].
9. Sysoev Ju.I., Titovich I.A., Okovityj S.V. Proizvodnye jetanolamina kak nejroprotektornye sredstva [Ethanolamine derivatives as neuroprotective agents]. Pharmacy. 2019;1:48–55. (In Russian)].
10. Shustov E.B., Bolotova V.C. Biologicheskoe modelirovanie utomlenija pri fi zicheskih nagruzkah [Biological modeling of exercise fatigue]. Biomedicina [Journal Biomed]. 2013;3:95–104. (In Russian)].
11. Shustov E.B., Karkischenko V.N., Semenov H.H. Poisk zakonomernostej, opredeljajushhih antigipoksicheskuju aktivnost’ soedinenij s nootropnym i nejroprotektornym dejstviem [Search for patterns that determine the antihypoxic activity of compounds with nootropic and neuroprotective effects]. Biomedicina [Journal Biomed]. 2015;1:18–23. (In Russian)].
12. Aguiar C.J. Rocha-Franco J.A., Sousa P.A., et al. Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation. Cell Communication and Signaling. 2014;78(12):1–17.
13. Breuer J., Herich J., Schneider-Hohendorf T., et al. Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium. Mult. Scler. J. 2017;24:1871–1882.
14. Cai X., Zhu C., Xu Y., Jing Y., Yuan Y., Wang L., et al. Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways. Scientifi c Reports. Springer Nature. 2016;6(1):1–11.
15. He W., Miao F., Lin D., et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004;429:188.
16. Malanga G. New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger. Drug Metabolism Letters. 2012;6(1):54–59.
17. Marques-Aleixo I., Oliveira P.J., Moreira P.I., et al. Physical exercise as a possible strategy for brain protection: evidence from mitochondrial-mediated mechanisms. Prog. Neurobiol. 2012;99(2):149–162.
18. Oh S., Oliynyk S., Actoprotectors. New class of pharmacological agents. Seoul: Aprerio Publ., 2015:150.
19. Qiang F. Effect of Malate-oligosaccharide Solution on Antioxidant Capacity of Endurance Athletes. The Open Biomedical Engineering J. 2015;9:326–329.
20. Shipkowski K.A., Sanders J.M., McDonald J.D., et al. Comparative disposition of dimethylaminoethanol and choline in rats and mice following oral or intravenous administration. Toxicology and Applied Pharmacology. 2019:51.
21. Tang H., Lu J.Y., Zheng X., et al. The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem. Biophys. Res. Commun. 2008;375:562–565.
22. Yuan Y., Yaqiong X., Jingren X., et al. Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway. Molecular Medicine Reports. 2017;16(15). DOI: 10.3892/mmr.2017.7554.
23. Wu J.L., Wu Q.P., Huang J.M., et al. Effects of L-malate on physical stamina and activities of enzymes related to the malate-aspartate shuttle in liver of mice. Physiol. Res. 2007;56(2):213–220.
24. Zdzisińska B., Żurek A., Kandefer-Szerszeń M. AlphaKetoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use. Arch. Immunol. Ther. Exp. (Warsz). 2016;65(1):21–36.
Review
For citations:
Chistyakova E.Yu., Okovitiy S.V., Yuskovec V.N., Lisitskii D.S., Verveda A.B. Actoprotective Activity of Dimethylaminoethanol Compounds Combined with Intermediates of the Citric Acid Cycle. Journal Biomed. 2021;17(2):58-70. (In Russ.) https://doi.org/10.33647/2074-5982-17-2-58-70
Views:
426
Email this article 
