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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(1): 95-104


T.Yu. Matvienko1, D.A. Zavodovskyi1, D.N. Nozdrenko1, I.V. Mishchenko2, O.P. Motuziuk2, K.I. Bogutska1, Yu.P. Sklyarov3, Yu.I. Prylutskyy1

  1. Taras Shevchenko National University of Kyiv; е-mail:;
  2. Lesya Ukrainka Eastern European National University, Lutsk;
  3. O.O. Bogomolets National Medical University, Kyiv


The data regarding the analysis of the physiological and biochemical mechanisms of muscle fatigue and ways to prevent it are summarized. The effect of the most common endogenous and exogenous antioxidants in the biochemical processes in muscle fatigue was analyzed. It is shown that biocompatible, non-toxic water-soluble C60 fullerenes, which possess powerful antioxidative properties, promise great prospects in the correction of skeletal muscle fatigue caused by the destructive action of free radicals.

Keywords: skeletal muscles; muscle fatigue; free radicals; C60 fullerene.


  1. Tipton MC. Exercise physiology: people and ideas. Amsterdam: Elsevier. 1993; 510 p. PubMedCentral
  3. Mosso A. Fatigue (1904). Whitefish: Kessinger Publishing. 2008; 348 p.
  5. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res. 2004; 56(2): 157-70. CrossRef  
  6. Boyas S, Guervel A. Neuromuscular fatigue in healthy muscle: underlying factors and adaptation mechanisms. Ann Phys Rehabil Med. 2011; 54(2): 88-108. CrossRef PubMed
  8. Kostyukov AI, Day S, Hellstrom F, Radovanovic S, Ljubisavljevic M, Windhorst U, Johansson H. Fatiguerelated changes in electromyogram activity of cat gastrocnemius during frequency-modulated efferent stimulation. Neurosci. 2000; 97(4): 801-9. CrossRef  
  9. Kostyukov AI, Kalezic I, Serenko SG, Ljubisavljevic M, Windhorst U, Johansson H. Spreading of fatiguerelated effects from active to inactive parts in the medial gastrocnemius muscle of the cat. Eur J Appl Physiol. 2002; 86(4): 295-307. CrossRef PubMed
  11. Ervilha UF, Farina D, Arendt-Nielsen L, Graven-Nielsen T. Experimental muscle pain changes motor control strategies in dynamic contractions. Exp Brain Res. 2005; 164(2): 215-24. CrossRef PubMed
  13. Harris RC, Sale C. Beta-alanine supplementation in highintensity exercise. Med Sport Sci. 2012; 59: 1-17. CrossRef PubMed
  15. Kalezic I, Bugaychenko LA, Kostyukov AI, Pilyavskii AI, Ljubisavljevic M, Windhorst U. Fatigue-related depression of the feline monosynaptic gastrocnemiussoleus reflex. J Physiol. 2004; 556(Pt1): 283-96. CrossRef PubMed PubMedCentral
  17. Lehedza AV, Gorkovenko AV, Vereshchaka IV, Dornowski M, Kostyukov AI. Comparative analysis of electromyographic muscle activity of the human hand during cyclic turns of isometric effort vector of wrist in opposite directions. Fiziol Zh. 2015; 61(2): 3-14. CrossRef  
  18. Williams WO. Huxley's model of muscle contraction with compliance. J Elasticity. 2011; 105(1): 365-80. CrossRef  
  19. Cooke R. Modulation of the actomyosin interaction during fatigue of skeletal muscle. Muselé Nerve. 2007; 36(6): 756-77. CrossRef PubMed
  21. Pate E, Bhimani M, Franks-Skiba K, Cooke R. Reduced effect of pH on skitined rabbit psoas muscle mechanics at high temperatures: implications for fatigue. J Physiol. 1995; 486(3): 689-94. CrossRef PubMed PubMedCentral
  23. Debold EP, Beck SE, Warshaw DM. The effect of low pH on single skeletal muscle myosin mechanics and kinetics. Am J Physiol Cell Physiol. 2008; 295(1): 173-9. CrossRef PubMed PubMedCentral
  25. Walter G, Vandenborne K, Elliott M, Leigh JS. In vivo ATP synthesis rates in single human muscles during high intensity exercise. J Physiol. 1999; 519(Pt3): 901-10. CrossRef PubMed PubMedCentral
  27. Westerblad H, Allen DG, Lännergren J. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci. 2002; 17: 17-21. PubMed
  29. Dahlstedt AJ, Katz A, Westerblad H. Role of myoplasmic phosphate in contractile function of skeletal muscle: studies on creatine kinase-deficient mice. J Physiol. 2001; 533(2): 379-88. CrossRef PubMed PubMedCentral
  31. Dahlstedt AJ, Katz A, Wieringa B, Westerblad H. Is creatine kinase responsible for fatigue? Studies of skeletal muscle deficient of creatine kinase. FASEB J. 2000; 14(7): 982-90. PubMed
  33. Fryer MW, Owen VJ, Lamb GD, and Stephenson DG. Effects of creatine phosphate and Pi on Ca2+ movements and tension development in rat skinned skeletal muscle fibres. J Physiol. 1995; 482(1): 123-40. CrossRef PubMed PubMedCentral
  35. Allen DG, Lännergren J, Westerblad H. Muscle cell function during prolonged activity: cellular mechanisms of fatigue. Exp Physiol. 1995; 80(4): 497-527. CrossRef PubMed
  37. Ahern GP, Laver DR. ATP inhibition and rectification of a Ca2+-activated anion channel in sarcoplasmic reticulum of skeletal muscle. Biophys J. 1998; 74(5): 2335-51. CrossRef  
  38. Westerblad H, Bruton JD, Lännergren J. The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature. J Physiol. 1997; 500(Pt1): 193-204. CrossRef PubMed PubMedCentral
  40. Wiseman RW, Beck TW, Chase PB. Effect of intracellular pH on force development depends on temperature in intact skeletal muscle from mouse. Am J Physiol Cell Physiol 1996; 271(3 Pt1): 878-86.
  42. Bangsbo J, Madsen K, Kiens B, Richter EA. Effect of muscle acidity on muscle metabolism and fatigue during intense exercise in man. J Physiol. 1996; 495(Pt2): 587-96. CrossRef PubMed PubMedCentral
  44. Nelson DL, Lehninger MC. Principles of biochemistry. New York: WH Freeman and company, 2008; 1158 p.
  46. Greer F, Friars D, Graham TE. Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance. J Appl Physiol. 2000; 89(5): 1837-44. PubMed
  48. Barreiro E, Gea J, Di Falco M, Kriazhev L, James S, Hussain SN. Protein carbonyl formation in the diaphragm. Am J Respir Cell Mol Biol. 2005; 32(1): 9-17. CrossRef PubMed
  50. Tsakiris S, Parthimos T, Parthimos N, Tsakiris T, Schulpis KH. The beneficial effect of L-cysteine supplementation on DNA oxidation induced by forced training. Pharmacol Res. 2006; 53(4): 386-90. CrossRef PubMed
  52. Vasilaki A, Mansouri A, Remmen H, van der Meulen, JH, Larkin L, Richardson AG, McArdle A, Faulkner JA, Jackson MJ. Free radical generation by skeletal muscle of adult and old mice: effect of contractile activity. Aging Cell. 2006; 5(2): 109-17. CrossRef PubMed
  54. Hasegawa A, Suzuki S, Matsumoto Y, Okubo T. In vivo fatiguing contraction of rat diaphragm produces hydroxyl radicals. Free Radic Biol Med. 1997; 22(1-2): 349-54. CrossRef  
  55. Stamler J, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001; 81(1): 209-37. PubMed
  57. Abraham RZ, Miller CC, Reid MB. The contractile response to nitric oxide (NO) varies among skeletal muscle. Endothelium. 1995; 3: 108.
  59. Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E, de Meirleir K. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc. 2005; 37(10): 1647-54. CrossRef PubMed
  61. McIver K L, Evans C, Kraus RM, Ispas L, Sciotti VM, Hickner RC. NO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibromyalgia. Pain. 2005; 120(1-2): 161-9. CrossRef PubMed
  63. Andrade FH, Reid MB, Allen DG, Westerblad H. Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from mouse. J Physiol. 1998; 509(Pt2): 565-75. CrossRef PubMed PubMedCentral
  65. Leeuwenburgh C, Hollander J, Leichtweis S, Griffiths M, Gore M, Ji LL. Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. Am J Physiol Regul Integr Comp Physiol. 1997; 272 (1 Pt2): 363-9.
  67. Moopanar TR, Allen DG. Reactive oxygen species reduce myofibrillar calcium sensitivity in fatiguing mouse skeletal muscle at 37°C. J Physiol. 2005; 564(Pt1): 189-99. CrossRef PubMed PubMedCentral
  69. Kanter M. Free radicals, exercise and antioxidant supplementation. Proc Nutr Soc. 1998; 57(1): 9-13. CrossRef PubMed
  71. Ji LL. Exercise sport science reviews: Exercise and oxidative stress: Role of the cellular antioxidant systems. Exerc Sport Sci Rev. 1995; 23(1): 135-66. PubMed
  73. Clanton TL, Zuo L, Klawitter P. Oxidants and skeletal muscle function: physiologic and pathophysiologic implications. Proc Soc Exp Biol Med. 1999; 222(3): 253-62. CrossRef PubMed
  75. Ji LL. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med. 2000; 222(3): 283-92. CrossRef  
  76. Katz A, Hernández A, Caballero DM, Briceno JF, Amezquita LV, Kosterina N, Bruton JD, Westerblad H. Effects of N-acetylcysteine on isolated mouse skeletal muscle: contractile properties, temperature dependence, and metabolism. Pflugers Arch. 2014; 466(3): 577-85. CrossRef PubMed
  78. Trice I, Haymes EM. Effects of caffeine ingestion on exerciseinduced changes during high-intensity, intermittent exercise. Int J Sport Nutr. 1995; 5(1): 37-44. CrossRef PubMed
  80. Pasman WJ, van Baak MA, Jeukendrup AE. The effect of different dosages of caffeine on endurance performance time. Int J Sports Med. 1995; 16(4): 225-30. CrossRef PubMed
  82. Graham TE, Spriet LL. Metabolic, catecholamine, and exercise performance responses to various doses of caffeine. J Appl Physiol. 1995; 78(3): 867-4. PubMed
  84. Mohr T, van Soeren M, Graham TE. Caffeine ingestion and metabolic responses of tetraplegic humans during electrical cycling. J Appl Physiol. 1998; 85(3): 979-85. PubMed
  86. Cohen BS, Nelson AG, Prevost MC. Effects of caffeine ingestion on endurance racing in heat and humidity. Eur J Appl Physiol. 1996; 73(3-4): 358-63. CrossRef  
  87. Jackman M, Wendling P, Friars D. Metabolic, catecholamine, and endurance responses to caffeine during intense exercise. J Appl Physiol. 1996; 81(4): 1658-63. PubMed
  89. Tarnopolsky MA, Cupido C. Caffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. J Appl Physiol. 2000; 89(5): 1719-24. PubMed
  91. Raguso CA, Coggan AR, Sidossis LS. Effect of theophylline on substratemetabolismduring exercise. Metabolism. 1996; 45(9): 1153-60. CrossRef  
  92. Graham TE, Helge JW, MacLean DA. Caffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exercise. J Physiol. 2000; 529(Pt3): 837-47. CrossRef PubMed PubMedCentral
  94. Laurent D, Scheider KE, Prusaczyk WK. Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise. J Clin Endocrinol Metab. 2000; 85(6): 2170-5. CrossRef  
  95. Chesley A, Howlett RA, Heigenhauser JF. Regulation of muscle glycogenolytic flux during intense aerobic exercise after caffeine ingestion. Am J Physiol. 1998; 275(2 Pt2): 596-603.
  97. MacIntosh BR, Wright BM. Caffeine ingestion and performance of a 1500 meter swim. Can J Appl Physiol. 1995; 20(2): 168-77. CrossRef PubMed
  99. Kalmar JM, Cafarelli E. Effects of caffeine on neuromuscular fatigue. J Appl Physiol. 1999; 87(2): 801-8. PubMed
  101. Tullberg M, Alstergren PJ, Ernberg MM. Effects of lowpower laser exposure on masseter muscle pain and microcirculation. Pain. 2003; 105(1-2): 89-96. CrossRef  
  102. Silveira PC, Silva LA, Fraga DB, Freitas TP, Streck EL, Pinho R. Evaluation of mitochondrial respiratory chain activity in muscle healing by low-level laser therapy. J Photochem Photobiol B. 2009; 95(2): 89-92. CrossRef PubMed
  104. Avni D, Levkovitz S, Maltz L, Oron U. Protection of skeletal muscles from ischemic injury: low-level laser therapy increases antioxidant activity. Photomed Laser Surg. 2005; 23(3): 273-7. CrossRef PubMed
  106. Rizzi CF, Mauriz JL, Freitas Correa DS. Effects of lowlevel laser therapy (LLLT) on the nuclear factor (NF)- kappaB signaling pathway in traumatized muscle. Lasers Surg Med. 2006; 38(7): 704-13. CrossRef PubMed
  108. Lopes-Martins RA, Marcos RL, Leonardo PS. Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle fatigue induced by electrical stimulation in rats. J Appl Physiol. 2006; 101(1): 283-8. CrossRef PubMed
  110. Leal Junior EC, Lopes-Martins RA, de Almeida P, Ramos L, Iversen VV, Bjordal JM. Effect of low-level laser therapy (GaAs 904 nm) in skeletal muscle fatigue and biochemical markers of muscle damage in rats. Eur J Appl Physiol. 2010; 108(6): 1083-8. CrossRef PubMed
  112. Mach J, Midgley AW, Dank S, Grant R, Bentley DJ. The effect of antioxidant supplementation on fatigue during exercise: potential role for NAD+(H). Nutrients. 2010; 2(3): 319-29. CrossRef PubMed PubMedCentral
  114. Prylutska SV, Grynyuk II, Matyshevska OP, Prylutskyy YuI, Ritter U, Scharff P. Anti-oxidant properties of C60 fullerenes in vitro. Fullerenes, Nanotubes, Carbon Nanostruct. 2008; 16(5-6): 698-705. CrossRef  
  115. Ritter U, Prylutskyy YuI, Evstigneev MP, Davidenko NA, Cherepanov VV, Senenko AI, Marchenko OA, Naumovets AG. Structural features of highly stable reproducible C60 fullerene aqueous colloid solution probed by various techniques. Fullerenes, Nanotubes, Carbon Nanostruct. 2015; 23(6): 530-4. CrossRef  
  116. Sun T, Xu Z. Radical scavenging activities of alpha-alanine C60 adduct. Bioorg Med Chem Lett. 2006; 16(14): 3731-4. CrossRef PubMed
  118. Lai HS, Chen WJ, Chiang LY. Free radical scavenging activity of fullerenol on the ischemia-reperfusion intestine in dogs. World J Surg. 2000; 24(4): 450-4. CrossRef PubMed
  120. Chen YW, Hwang KC, Yen CC, Lai YL. Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am J Physiol Regul Integr Comp Physiol. 2004; 287(1): 21-6. CrossRef PubMed
  122. Lai YL, Murugan P, Hwang KC. Fullerene derivative attenuates ischemia-reperfusion-induced lung injury. Life Sci. 2003; 72(11): 1271-8. CrossRef  
  123. Cataldo F, Da Ros T. Medicinal chemistry and pharmacological potential of fullerenes and carbon nanotubes. Berlin: Springer. 2008; 408 p. CrossRef  
  124. Wilson SR. Biological aspects of fullerenes. Fullerenes: Chemistry, Physics and Technology. 2000; 437-65.
  126. Andreichenko KS, Prylutska SV, Medynska KO, Bogutska KI, Nurishchenko NE, Prylutskyy YuI, Ritter U, Scharff P. Effect of fullerene C60 on ATPase activity and superprecipitation of skeletal muscle actomyosin. Ukr Biochem J. 2013; 85(2): 20-6. CrossRef  
  127. Ashcroft JM, Tsyboulski DA, Hartman KB. Fullerene C60 immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody. Chem Commun. 2006; 28: 3004-6. CrossRef PubMed
  129. Prylutska SV, Burlaka AP, Prylutskyy YuI. Pristine C60 fullerenes inhibit the rate of tumor growth and metastasis. Exp Oncol. 2011; 33(3): 162-4. PubMed
  131. Prylutska SV, Burlaka AP, Klymenko PP. Using watersoluble C60 fullerenes in anticancer therapy. Cancer Nanotechnol. 2011; 2(1-6): 105-10. CrossRef PubMed PubMedCentral
  133. Panchuk RR, Prylutska SV, Chumak VV, Skorokhyd NR, Lehka LV, Evstigneev MP, Prylutskyy YuI, Berger W, Heffeter P, Scharff P, Ritter U, Stoika RS. Application of C60 fullerene-doxorubicin complex for tumor cell treatment in vitro and in vivo. J Biomed Nanotechnol. 2015; 11(7): 1139-52. CrossRef PubMed
  135. Halenova TI, Vareniuk IM, Roslova NM, Dzerzhynsky ME, Savchuk OM, Ostapchenko LI, Prylutskyy YuI, Ritter U, Scharff P. Hepatoprotective effect of orally applied water-soluble pristine C60 fullerene against CCl4-induced acute liver injury in rats. RSC Adv. 2016; 6(102): 100046-55. CrossRef  
  136. Mori T, Takada H, Ito S. Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis. Toxicology. 2006; 225(1): 48-54. CrossRef PubMed
  138. Wang IC, Tai LA, Lee DD. C60 and water-soluble fullerene derivatives as antioxidants against radicals-initiated lipid peroxidation. J Med Chem. 1999; 42(22): 4614-20. CrossRef PubMed
  140. Gharbi N, Pressac M, Hadchouel M. Fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005; 5(12): 2578-85. CrossRef PubMed
  142. Xiao L, Takada H, Gan X, Miwa N. The water-soluble fullerene derivative «radicalsponge» exerts cytoprotective action against UV irradiation but not visible-lightcatalyzed cytotoxicity in human skin keratinocytes. Bioorg Med Chem Lett. 2006; 16(5): 1590-5. CrossRef PubMed

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