Keywords: aerobic loads, succinic acid, oxygen transport function of blood, erythrocyte membranes, lipid peroxidation


Introduction. Strenuous aerobic work inherent to cyclical sports requires adequate oxygenation of the athletes’ working muscles. One of the ways to improve the oxygen transport function of blood is to optimize the structural and functional state of erythrocytes, for example, by using succinic acid in the form of the medical drug Armadin Long. This pharmacological drug is widespread in clinical practice for treating hypoxic and ischemic conditions, and very little is known about its use for improving the condition of the erythrocytes in the blood of athletes, which determined the relevance of this study.

The objective of the study was to assess the feasibility and effectiveness of using the medical drug Armadine Long to improve the state of the erythrocyte link of the blood oxygen transport system during aerobic exercise.

Materials and Methods. A randomized blinded placebo-controlled trial included 40 male middle-distance runners (aerobic discipline of athletics). The subjects were divided into two subgroups matched for number, age, and anthropometric characteristics (strats). In this work, laboratory methods were used, including hematological tests (in particular, hemoglobin and erythrocytes level measurement and erythrocyte characteristics evaluation), as well as biochemical method: the study of prooxidant and antioxidant balance (activity of lipid peroxidation according to changes in the content of maloniс dialdehyde and antioxidant protection according to changes in the concentration of reduced glutathione) and functional characteristics of erythrocyte membranes (permeability, sorption capacity, sorption capacity of the glycocalyx) as well as evaluation of the main components of lipid and protein composition of red blood cell membranes. Pedagogical research methods were based on the determination of relative aerobic capacity using the generally accepted PWC170 test.

Results of the study. During 21 days of intensive loads, an almost two-fold increase in contents of malonic dialdehyde was observed with a parallel decrease in reduced glutathione content by 23.5 % during aerobic loads. At the same time, there was a deterioration of the functional characteristics of erythrocytes and a decrease in the relative aerobic capacity in comparison with the baseline data.

The use of the medical drug Armadine Long at a dose of 600 mg per day improved the indicated characteristics of erythrocytes. At the same time, there were positive changes in the protein and lipid state of the erythrocyte membranes, and the athletes’ aerobic power increased by 38.7%. It substantiates the high ergogenic ability of succinic acid, which is based on the normalization of the lipoperoxidation process and the improvement of the structural and functional characteristics of erythrocyte membranes.

Author Biographies

Larisa Gunina, Educational and Scientific Olympic Institute, National Ukraine University of Physical Education and Sports, Kyiv, Ukraine

Deputy Director for Scientific and Pedagogical Work of the Educational and Scientific Olympic Institute, Doctor of Biological Sciences, Professor, National Ukraine University of Physical Education and Sports, Kyiv, Ukraine (, e-mail:

Yurii Ataman, Department of Physical Therapy, Occupational Therapy, and Sports Medicine of the Medical Institute, Sumy State University, Sumy, Ukraine

Head of the Department of Physical Endurance, Occupational Therapy and Sports Medicine of the Medical Institute, Doctor of Medical Sciences, Professor, Sumy State University, Sumy, Ukraine (, e-email:

Ihor Belenichev, Department of Pharmacology and Medical Formulation with a Course of Normal Physiology, Zaporizhzhia Medical University, Zaporizhzhia, Ukraine

Head of the Department of Pharmacology and Medical Formulation with a Course of Normal Physiology, Doctor of Medical Sciences, Professor, Zaporizhzhia Medical University, Zaporizhzhia, Ukraine (, e-mail:

Roman Golovashchenko, Department of Physical Education, Sports, and Health, State Tax University, Irpin, Ukraine

acting Head of the Department of Physical Education, Sports and Health, Candidate of Sciences in Physical Education and Sports, Associate Professor, State Tax University, Irpin, Ukraine (, e-mail:

Valentina Voitenko, Department of Physical Therapy, Occupational Therapy, and Sports Medicine of the Medical Institute, Sumy State University, Sumy, Ukraine

assistant professor of the Department of Physical Endurance, Occupational Therapy and Sports Medicine of the Medical Institute, Doctor of Philosophy in Biological Sciences, Sumy State University, Sumy, Ukraine (, e-mail:

Victoria Bezugla, Educational and Scientific Olympic Institute, National Ukraine University of Physical Education and Sports, Kyiv, Ukraine

teacher of the Department of Physical Therapy and Occupational Therapy, National Ukraine University of Physical Education and Sports, Kyiv, Ukraine (, e-mail:


1. Gunina L, Voitenko V. Diagnostic and therapeutic approaches to the treatment of iron deficiency conditions in athletes. Sporto Mokslas. 2022;1(101):42−49.
2. Périard JD, Travers GJS, Racinais S, Sawka MN. Cardiovascular adaptations supporting human exercise−heat acclimation. Auton. Neurosci. 2016;196:52−62. doi: 10.1016/j.autneu.2016.02.002.
3. Weight LM, Klein M, Noakes TD, Jacobs P. «Sports anemia» − A real or apparent phenomenon in endurance-trained athletes? Int. J. Sports Med. 1992;13:344−347. doi: 10.1055/s−2007−1021278.
4. Damian MT, Vulturar R, Login CC, Damian L, Chis A, Bojan A. Anemia in Sports: A Narrative Review. Life (Basel). 2021;11(9):987. doi: 10.3390/life11090987.
5. Eichner ER. Athletes, Anemia, and Iron Redux. Curr. Sports Med. Rep. 2021;20(7):335−336. doi: 10.1249/JSR.0000000000000856.
6. Muñoz Marín D, Barrientos G, Alves J, Grijota FJ, Robles MC, Maynar M. Oxidative stress, lipid peroxidation indexes and antioxidant vitamins in long and middle distance athletes during a sport season. J. Sports Med. Phys. Fitness. 2018;58(12):1713−1719. doi: 10.23736/S0022−4707.17.07887-2.
7. Gomez-Cabrera MC, Carretero A, Millan-Domingo F, Garcia-Dominguez E, Correas AG, Olaso-Gonzalez G, Viña J. Redox-related biomarkers in physical exercise. Redox Biol. 2021;42:101956. doi: 10.1016/j.redox.2021.101956.
8. Wang F, Wang X, Liu Y, Zhang Z. Effects of Exercise-Induced ROS on the Pathophysiological Functions of Skeletal Muscle. Oxid. Med. Cell Longev. 2021;2021:3846122. doi: 10.1155/2021/3846122.
9. Ramos A, Coutinho P, Davids K, Mesquita I. Developing Players' Tactical Knowledge Using Combined Constraints-Led and Step-Game Approaches-A Longitudinal Action-Research Study. Res. Q Exerc. Sport. 2021;92(4):584−598. doi: 10.1080/02701367.2020.1755007.
10. Platonov V, Nikitenko A. Agility and coordination testing in hand-to-hand combat sports. Polish Journal of Sport and Tourism. 2019;26(2):7−13.
11. Paskausky AL, Simonelli MC. Measuring grade inflation: a clinical grade discrepancy score. Nurse Educ. Pract. 2014;14(4):374−379. doi: 10.1016/j.nepr.2014.01.011.
12. Gunina LM, Shustov YeB, Belenichev IF, Vysochina NL, Golovashchenko RV, Morozova OV. Specialized nutrition for athletes: evaluation of ergogenic action using the principles of evidence-based medicine. Pharmacia. 2022;69(1):37−44. doi:10.3897/pharmacia.69.e76599.
13. Gunina LM, Rybina IL, Ataman YuA, Voitenko VL. Oxidative stress as a factor in the deterioration of oxygen transfer during exercise (review). Physiol. J. 2021;67(5):54−63. doi:
14. Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE, Paschini M, Paulo JA, Garrity R, Laznik-Bogoslavski D, Ferreira JCB, Carl CS, Sjøberg KA, Wojtaszewski JFP, Jeppesen JF, Kiens B, Gygi SP, Richter EA, Mathis D, Chouchani ET. pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise. Cell. 2020;183(1):62−75. doi: 10.1016/j.cell.2020.08.039.
15. Voitenko VL, Gunina LM. [The effect of succinic acid on changes in the mitochondrial apparatus of skeletal muscle cells during simulation of physical exertion in the experiment]. Ukrainian J. Med., Biol. Sports. 2021;6(1/29):293−302. doi: 10.26693/jmbs06.01.293.
16. Storz JF, Bautista NM. Altitude acclimatization, hemoglobin−oxygen affinity, and circulatory oxygen transport in hypoxia. Mol. Aspects Med. 2022;84:101052. doi: 10.1016/j.mam.2021.101052.
17. Wehrlin JP, Marti B, Hallén J. Hemoglobin Mass and Aerobic Performance at Moderate Altitude in Elite Athletes. Adv. Exp. Med. Biol. 2016;903:357−374. doi: 10.1007/978-1-4899-7678-9_24.
18. Mendanha SA, Anjos JL, Silva AH, Alonso A. Electron paramagnetic resonance study of lipid and protein membrane components of erythrocytes oxidized with hydrogen peroxide. Braz. J. Med. Biol. Res. 2012;45(6):473−481. doi: 10.1590/s0100−879x2012007500050.
19. Antonelou MH, Kriebardis AG, Velentzas AD. Oxidative stress-associated shape transformation and membrane proteome remodeling in erythrocytes of end stage renal disease patients on hemodialysis. J. Proteomics. 2011;74(11):2441−2452. doi: 10.1016/j.jprot.2011.04.009.
20. Gunina LM, Orel VE, Savosta AV, Tymchenko AS. [Surface architectonics of the cytoskeleton of erythrocytes in normal conditions and during metabolic changes in the body]. Ukraine J. Hematol. Transfusiol. 2008;(2):5−13.
21. Farmakologiya sporta [Sport Pharmacology]; eds. SA Oleinik, LM Gunina, RD Seifulla. Kyiv, Olympic Literature Publ., 2010. 639 c.
22. Kirichek LT, Shcherban NG. [Metabolic and metabolitotropic drugs in the stress protection system]. Int. Med. J. 2012;(2):103–108.
23. Semko GA. [Structural and functional changes in membranes and outer membrane layers of erythrocytes in hyperepidermopoiesis]. Ukr. Biochem. J. 1998;70:113−118.
24. Bankova VV, Prishchepova NF, Avratinsky OI. [A method for assessing pathological changes in the plasma membrane in children with various diseases]. Pathol. Physiol. Exp. Therapy.1987;(3):78−81.
25. Shvets NI, Davydov VV. [Age-related features of changes in the glutathione system in the heart of rats under immobilization stress]. Ukr. Biochem. J. 2008;80 6):74–78.
26. Mikhailovich VA, Marusanov VE, Bichun AB. [The permeability of the erythrocyte membrane and its sorption capacity are the optimal criteria for the severity of endogenous intoxication]. Anesthesiol. Reanimathol. 1993;(5):66−69.
27. Borisov YuA, Spiridonov VN, Suglobova ED. [RBC Membrane Resistance: Mechanisms, Tests, Evaluation (Literature Review)]. Clin. Lab. Diagn. 2007;(12):36–40.
28. Menshikov VV. Laboratornyie issledovaniya v klinike (monografiya) [Laboratory research in the clinic (monograph)]. Leningrad: Science Publ., 1990. 327 с.
29. Biologicheskie membrany. [Metodyi Biological membranes. Methods]; ed. J. Findlay, W. Evans: from English. Moskow: MIR Publ., 1990. pp. 184−186.
30. Holm TM, Braun A, Trigatti BL, Brugnara C, Sakamoto M, Krieger M, Andrews NC. Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI. Blood. 2002;99(5):1817−1824. doi: 10.1182/blood.v99.5.1817.
31. Gridin LA, Ikhalainen AA, Bogomolov AV, Kovtun AP, Kukushkin YuA. Metodyi issledovaniya i farmakologicheskoy korrektsii fizicheskoy rabotosposobnosti cheloveka; pod red. akademika RAN I.B. Ushakova. [Research methods and pharmacological correction of human physical performance; ed. Academician of the Russian Academy of Sciences I.V. Ushakov] Moscow: Medicine Publ., 2007. 348 с.
32. N'guessan BB, Asiamah AD, Arthur NK, Frimpong-Manso S, Amoateng P, Amponsah SK, Kukuia KE, Sarkodie JA, Opuni KF, Asiedu-Gyekye IJ, Appiah-Opong R. Ethanolic extract of Nymphaea lotus L. (Nymphaeaceae) leaves exhibits in vitro antioxidant, in vivo anti-inflammatory and cytotoxic activities on Jurkat and MCF-7 cancer cell lines. BMC Complement. Med. Ther. 2021;21(1):22. doi: 10.1186/s12906-020-03195-w.
33. Schmid F, Barrett MJP, Obrist D, Weber B, Jenny P. Red blood cells stabilize flow in brain microvascular networks. PLoS Comput Biol. 2019;15(8):e1007231. doi: 10.1371/journal.pcbi.1007231.
34. Meyer PAR. Re-orchestration of blood flow by microcirculations. Eye (Lond). 2018;32(2):222−229. doi: 10.1038/eye.2017.315.
35. Soulsbury CD, Dobson J, Deeming DC, Minias P. Energetic Lifestyle Drives Size and Shape of Avian Erythrocytes. Integr. Comp. Biol. 2022;62(Issue 1):71–80.
36. Pingitore A, Lima GP, Mastorci F, Quinones A, Iervasi G, Vassalle C. Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports. Nutrition. 2015;31(7−8):916−922. doi: 10.1016/j.nut.2015.02.005.
37. Adak S, Chowdhury S, Bhattacharyya M. Dynamic and electrokinetic behavior of erythrocyte membrane in diabetes mellitus and diabetic cardiovascular disease. Biochim. Biophys. Acta. 2008;1780(2):108−115. doi: 10.1016/j.bbagen.2007.10.013.
38. Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative Stress in Atherosclerosis. Curr. Atheroscler. Rep. 2017;19(11):42. doi: 10.1007/s11883-017-0678-6.
39. Klaunig JE. Oxidative Stress and Cancer. Curr. Pharm. Des. 2018;24(40):4771−4778. doi: 10.2174/1381612825666190215121712.
40. de Oliveira DCX, Rosa FT, Simões−Ambrósio L, Jordao AA, Deminice R. Antioxidant vitamin supplementation prevents oxidative stress but does not enhance performance in young football athletes. Nutrition. 2019;63-64:29−35. doi: 10.1016/j.nut.2019.01.007.
41. Cazzola R, Russo−Volpe S, Cervato G, Cestaro B. Biochemical assessments of oxidative stress, erythrocyte membrane fluidity and antioxidant status in professional soccer players and sedentary controls. Eur. J. Clin. Invest. 2003;33(10):924−930. doi: 10.1046/j.1365-2362.2003.01227.x.
42. Wan J, Forsyth AM, Stone HA. Red blood cell dynamics: from cell deformation to ATP release. Integr. Biol. (Camb.). 2011;3(10):972−81. doi: 10.1039/c1ib00044f.
43. Ferguson BS, Neidert LE, Rogatzki MJ, Lohse KR, Gladden LB, Kluess HA. Red blood cell ATP release correlates with red blood cell hemolysis. Am. J. Physiol. Cell Physiol. 2021;321(5):C761−C769. doi: 10.1152/ajpcell.00510.2020.
44. Dufour SP, Patel RP, Brandon A, Teng X, Pearson J, Barker H, Ali L, Yuen AH, Smolenski RT, González-Alonso J. Erythrocyte-dependent regulation of human skeletal muscle blood flow: role of varied oxyhemoglobin and exercise on nitrite. Am. J. Physiol. Heart. Circ. Physiol. 2010;299(6):H1936−1946. doi: 10.1152/ajpheart.00389.2010.
45. Travers G, Kippelen P, Trangmar SJ, González-Alonso J. Physiological Function during Exercise and Environmental Stress in Humans. An Integrative View of Body Systems and Homeostasis. Cells. 2022;11(3):383. doi: 10.3390/cells11030383.
46. Stovell MG, Mada MO, Helmy A, Carpenter TA, Thelin EP, Yan JL, Guilfoyle MR, Jalloh I, Howe DJ, Grice P, Mason A, Giorgi-Coll S, Gallagher CN, Murphy MP, Menon DK, Hutchinson PJ, Carpenter KLH. The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury. Sci. Rep. 2018;8(1):11140. doi: 10.1038/s41598-018-29255-3.
47. Kovaleva OV, Nikishkin IA, Raspopova NI, Kozyro VI. Effect of metabolites on the activity of enzymes protecting the stability of the erythrocyte membrane in experimental decompression sickness. Fiziol Zh. 1991;37(4):115−119. PMID: 1778246.
48. Galle FA, Martella D, Bresciani G. Antioxidant and anti-inflammatory modulation of exercise during aging. Rev. Esp. Geriatr. Gerontol. 2018;53(5):279−284. doi: 10.1016/j.regg.2018.03.003.
How to Cite
Larisa Gunina, Yurii Ataman, Ihor Belenichev, Roman Golovashchenko, Valentina Voitenko, & Victoria Bezugla. (2022). DETERMINATION OF THE INFLUENCE MECHANISMS OF SUCCINIC ACID-BASED DRUG ON IMPROVING THE STATE OF ERYTHROCYTE LINK OF OXYGEN TRANSPORT DURING AEROBIC PHYSICAL LOADS. Eastern Ukrainian Medical Journal, 10(3), 247-258.;10(3):247-258