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Journal of Physiology and Biochemistry

, Volume 74, Issue 3, pp 359–367 | Cite as

Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles

  • Anand Thirupathi
  • Ricardo A. Pinho
Review

Abstract

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.

Keywords

Reactive oxygen species Oxidative stress Antioxidants Physical exercise 

Abbreviations

α-KGDH

Alpha-ketoglutarate dehydrogenase

ARE

Antioxidant response elements

ATP

Adenosine triphosphate

BTB

Tram track and bric-a-brac

CAT

Catalase

CoQ

Ubiquinone

CTR

C-terminal region

ETC

Electron transport chain

FMN

Flavin mononucleotide

FeS

Ferrous sulfide

GPx

Glutathione peroxidase

H2O2

Hydrogen peroxide

IVR

Linker intervening region

Keap 1

Kelch-like ECH-associated protein

Maf

Musculoaponeurotic fibrosarcoma oncogene

NADH

Nicotinamide adenine dinucleotide dehydrogenase

NAD

Nicotinamide adenine dinucleotide

NAD(P)H

Nicotinamide adenine dinucleotide phosphate

Nrf2

Nuclear factor (erythroid-derived 2)-like 2

PDH

Pyruvate dehydrogenase

RET

Reverse electron transport

ROS

Reactive oxygen species

SOD1

Superoxide dismutase 1

SOD2

Superoxide dismutase 2

TCA

Tricarboxylic acid cycle

UCP3

Uncoupling protein 3

Notes

Funding information

This work was supported by the Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil, and Coordination for the Improvement of Higher Education Personnel-CAPES, Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Alessio HM, Goldfarb AH, Cutler RG (1988) MDA content increases in fast- and slow-twitch skeletal muscle with intensity of exercise in a rat. Am J Physiol Cell Physiol 255:C874–C877CrossRefGoogle Scholar
  2. 2.
    Andreyev AY, Kushnareva YE, Murphy AN, Starkov AA (2015) Mitochondrial ROS metabolism: 10 years later. Biochemistry (Mosc) 80:517–531CrossRefGoogle Scholar
  3. 3.
    Bailey DM, Lawrenson L, McEneny J, Young IS, James PE, Jackson SK, Henry RR, Mathieu-Costello O, McCord JM, Richardson RS (2007) Electron paramagnetic spectroscopic evidence of exercise-induced free radical accumulation in human skeletal muscle. Free Radic Res 41:182–190CrossRefPubMedGoogle Scholar
  4. 4.
    Barbe MF, Barr AE (2006) Inflammation and the pathophysiology of work-related musculoskeletal disorders. Brain Behav Immun 20:423–429CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Barbieri E, Sestili P (2012) Reactive oxygen species in skeletal muscle signaling. J Signal Transduct 2012:1–17CrossRefGoogle Scholar
  6. 6.
    Bendich A (1991) Exercise and free radicals: effect of antioxidant vitamins. Med Sport Sci 32:59–78CrossRefGoogle Scholar
  7. 7.
    Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease and oxidative stress. J Biol Chem 272:20313–20316CrossRefPubMedGoogle Scholar
  8. 8.
    Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134:707–716CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brady PS, Brady LJ, Ullrey DE (1979) Selenium, vitamin E and the response to swimming stress in the rat. J Nutr 109:1103–1109CrossRefPubMedGoogle Scholar
  10. 10.
    Bryer SC, Goldfarb AH (2006) Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise. Int J Sport Nutr Exerc Metab 16:270–280CrossRefPubMedGoogle Scholar
  11. 11.
    Clarkson PM, Thompson HS (2000) Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr 72:637S–646SCrossRefPubMedGoogle Scholar
  12. 12.
    Commoner B, Townsend J, Pake GE (1954) Free radicals in biological materials. Nature 174:689–691CrossRefPubMedGoogle Scholar
  13. 13.
    Contreras L, Drago I, Zampese E, Pozzan T (2010) Mitochondria: the calcium connection. Biochim Biophys Acta 1797:607–618CrossRefPubMedGoogle Scholar
  14. 14.
    Davies KJA, Quintanilha AT, Brooks GA, Pecker L (1982) Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107:1198–1205CrossRefPubMedGoogle Scholar
  15. 15.
    Dillard CJ, Litov RE, Savin WM, Dumelin EE, Tappel AL (1978) Effects of exercise, vitamin-E, and ozone on pulmonary-function and lipid peroxidation. J Appl Physiol 45:927–932CrossRefPubMedGoogle Scholar
  16. 16.
    Dong J, Chen P, Wang R, Yu D, Zhang Y, Xiao W (2011) NADPH oxidase: a target for the modulation of the excessive oxidase damage induced by Overtraining in rat neutrophils. Int J Biol Sci 7:881–891CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95CrossRefPubMedGoogle Scholar
  18. 18.
    Drummond RM, Tuft RA (1999) Release of Ca2+ from the sarcoplasmic reticulum increases mitochondrial [Ca2+] in rat pulmonary artery smooth muscle cells. J Physiol 516:139–147CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415:96–99CrossRefPubMedGoogle Scholar
  20. 20.
    Ferrari RS, Andrade CF (2015) Oxidative stress and lung ischemia-reperfusion injury. Oxidative Med Cell Longev 2015:590987CrossRefGoogle Scholar
  21. 21.
    Gardner PR, Fridovich I (1991) Superoxide sensitivity of the Escherichia coli aconitase. J Biol Chem 266:19328–19333PubMedGoogle Scholar
  22. 22.
    Gomez-Cabrera MC, Domenech E, Viña J (2008) Moderate exercise is an antioxidant: upregulation of antioxidantgenes by training. Free Radic Biol Med 44:126–131CrossRefPubMedGoogle Scholar
  23. 23.
    Goncalves RL, Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Brand MD (2015) Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. J Biol Chem 290:209–227CrossRefPubMedGoogle Scholar
  24. 24.
    Gounder SS, Kannan S, Devadoss D, Miller CJ, Whitehead KS, Odelberg SJ, Firpo MA, Paine R, Hoidal JR, Abel ED, Rajasekaran NS (2012) Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training. PLoS One 7:e45697CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Guo J, Lemire BD (2003) The ubiquinone-binding site of the Saccharomyces cerevisiae succinate-ubiquinone oxidoreductase is a source of superoxide. J Biol Chem 278:47629–47635CrossRefPubMedGoogle Scholar
  26. 26.
    Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH (2011) Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab 301:E779–E784CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Izzicupo P, Di Valerio V, D’ Amico MA, Di Mauro M, Pennelli A, Falone S, Alberti G, Amicarelli F, Miscia S, Gallina S, Di Baldassarre A (2010) NAD(P)H oxidase and pro-inflammatory response during maximal exercise: role of C242T polymorphism of the P22PHOX subunit. Int J Immunopathol Pharmacol 23:203–211CrossRefPubMedGoogle Scholar
  28. 28.
    Jackson MJ (1994) Exercise and oxygen radical production by muscle. In: Sen CK, Packer L, Hanninan O (eds) Exercise and oxygen toxicity. Elsevier, London, pp 49–57Google Scholar
  29. 29.
    Jackson MJ, Edwards RH, Symons MC (1985) Electron spin resonance studies of intact mammalian skeletal muscle. Biochim Biophys Acta 847:185–190CrossRefPubMedGoogle Scholar
  30. 30.
    Ji LL (2015) Redox signaling in skeletal muscle: role of aging and exercise. Adv Physiol Educ 39:352–359CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279:4127–4135CrossRefPubMedGoogle Scholar
  32. 32.
    Loschen G, Azzi A, Richter C, Flohe L (1974) Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett 42:68–72CrossRefPubMedGoogle Scholar
  33. 33.
    Mailloux RJ, Craig Ayre D, Christian SL (2016) Induction of mitochondrial reactive oxygen species production by GSH mediated S-glutathionylation of 2-oxoglutarate dehydrogenase. Redox Biol 8:285–297CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mason SA, Morrison D, McConell GK, Wadley GD (2016) Muscle redox signalling pathways in exercise. Role of antioxidants. Free Radic Biol Med 98:29–45CrossRefPubMedGoogle Scholar
  35. 35.
    Mastaloudis A, Leonard SW, Traber MG (2001) Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med 31:911–922CrossRefPubMedGoogle Scholar
  36. 36.
    McMahon M, Thomas N, Itoh K, Yamamoto M, Hayes JD (2004) Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron. J Biol Chem 279:31556–31567CrossRefPubMedGoogle Scholar
  37. 37.
    Meier P, Renga M, Hoppeler H, Baum O (2013) The impact of antioxidant supplements and endurance exercise on genes of the carbohydrate and lipid metabolism in skeletal muscle of mice. Cell Biochem Funct 31:51–59CrossRefPubMedGoogle Scholar
  38. 38.
    Messner KR, Imlay JA (2002) Mechanism of superoxide and hydrogen peroxide formation by fumaratereductase, succinate dehydrogenase, and aspartate oxidase. J Biol Chem 277:42563–42571CrossRefPubMedGoogle Scholar
  39. 39.
    Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10:549–557CrossRefPubMedGoogle Scholar
  40. 40.
    Moulin M, Ferreiro A (2016) Muscle redox disturbances and oxidative stress as pathomechanisms and therapeutic targets in early-onset myopathies. Semin Cell Dev Biol 64:213–223CrossRefPubMedGoogle Scholar
  41. 41.
    Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13CrossRefPubMedGoogle Scholar
  42. 42.
    Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L, Rajasekaran NS (2012) Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med 52:366–376CrossRefPubMedGoogle Scholar
  43. 43.
    Namakkal Soorappan R, Devdoss D, Kannan S, Olsen C, Subbanna Gounder S, Davidson CJ et al (2012) Abstract 30: endurance exercise induces cardiac hypertrophy in aged Nrf2−/− mice. Circ Res 111:A30–A30Google Scholar
  44. 44.
    Nioi P, Nguyen T, Sherratt PJ, Pickett CB (2005) The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation. Mol Cell Biol 25:10895–10906CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nunes-Silva A, Bernardes PT, Rezende BM, Lopes F, Gomes EC, Marques PE, Lima PM, Coimbra CC, Menezes GB, Teixeira MM, Pinho V (2014) Treadmill exercise induces neutrophil recruitment into muscle tissue in a reactive oxygen species-dependent manner. An intravital microscopy study. PLoS One 9:e96464CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Pinho RA, Silveira PCL, Piazza M, Tuon T, Slva GA, Dal-Pizzol F et al (2006) Regular physical exercises decrease the oxidant pulmonary stress in rats after acute exposure to mineral coal. Rev Bras Med Esporte 2:81–84CrossRefGoogle Scholar
  47. 47.
    Pinho RA, Sepa-Kishi DM, Bikopoulos G, Wu MV, Uthayakumar A, Mohasses A, Hughes MC, Perry CGR, Ceddia RB (2017) High-fat diet induces skeletal muscle oxidative stress in a fiber type-dependent manner in rats. Free Radic Biol Med 110:381–389CrossRefPubMedGoogle Scholar
  48. 48.
    Powers SK, Jackson MJ (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 88:1243–1276CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Powers SK, Ji LL, Leeuwenburgh C (1999) Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc 31:987–997CrossRefPubMedGoogle Scholar
  50. 50.
    Powers SK, Duarte J, Kavazis AN, Talbert EE (2010) Reactive oxygen species are signalling molecules for skeletal muscle adaptation. Exp Physiol 95:1–9CrossRefPubMedGoogle Scholar
  51. 51.
    Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Orr AL, Brand MD (2013) Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol 1:304–312CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Radák Z, Nakamura A, Nakamoto H, Asano K, Ohno H, Goto S (1998) A period of anaerobic exercise increases the accumulation of reactive carbonyl derivatives in the lungs of rats. Pflugers Arch 435:439–441CrossRefPubMedGoogle Scholar
  53. 53.
    Reid MB (2001) Redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol 90:724–731CrossRefPubMedGoogle Scholar
  54. 54.
    Reid MB (2016) Redox interventions to increase exercise performance. J Physiol 594:5125–5133CrossRefPubMedGoogle Scholar
  55. 55.
    Reid MB, Haack KE, Franchek KM, Valberg PA, Kobzik L, West MS (1992) Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro. J Appl Physiol 73:1797–1804CrossRefPubMedGoogle Scholar
  56. 56.
    Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A 106:8665–8670CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Silva LA, Silveira PC, Ronsani MM, Souza PS, Scheffer D, Vieira LC, Benetti M, De Souza CT, Pinho RA (2011) Taurine supplementation decreases oxidative stress in skeletal muscle after eccentric exercise. Cell Biochem Funct 29:43–49CrossRefPubMedGoogle Scholar
  58. 58.
    Silva LA, Tromm CB, Da Rosa G, Bom K, Luciano TF, Tuon T, De Souza CT, Pinho RA (2013) Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise. J Sports Sci 31:1164–1176CrossRefPubMedGoogle Scholar
  59. 59.
    Silva LA, Tromm CB, Bom KF, Mariano I, Pozzi B, da Rosa GL, Tuon T, da Luz G, Vuolo F, Petronilho F, Cassiano W, De Souza CT, Pinho RA (2014) Effects of taurine supplementation following eccentric exercise in young adults. Appl Physiol Nutr Metab 39:101–104CrossRefPubMedGoogle Scholar
  60. 60.
    Silveira PC, da Silva LA, Pinho CA, De Souza PS, Ronsani MM, Scheffer DL, Pinho RA (2013) Effects of low-level laser therapy (GaAs) in an animal model of muscular damage induced by trauma. Lasers Med Sci 28:431–436CrossRefPubMedGoogle Scholar
  61. 61.
    Sjödin B, HellstenWesting Y, Apple FS (1990) Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med 10:236–254CrossRefPubMedGoogle Scholar
  62. 62.
    Smith MA, Reid MB (2006) Redox modulation of contractile function in respiratory and limb skeletal muscle. Respir Physiol Neurobiol 151:229–241CrossRefPubMedGoogle Scholar
  63. 63.
    St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD (2002) Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277:44784–44790CrossRefPubMedGoogle Scholar
  64. 64.
    Thirupathi A, de Souza CT (2017) Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise. J Physiol Biochem:1–8Google Scholar
  65. 65.
    Torres R, Appell HJ, Duarte JA (2007) Acute effects of stretching on muscle stiffness after a bout of exhaustive eccentric exercise. Int J Sports Med 28:590–594CrossRefPubMedGoogle Scholar
  66. 66.
    Tretter L, Adam-Vizi V (2000) Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20:8972–8979CrossRefPubMedGoogle Scholar
  67. 67.
    Tretter L, Adam-Vizi V (2005) Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos Trans R SocLond B Biol Sci 360:2335–2345CrossRefGoogle Scholar
  68. 68.
    Vasquez-Vivar J, Kalyanaraman B, Kennedy MC (2000) Mitochondrial aconitase is a source of hydroxyl radical: an electron spin resonance investigation. J Biol Chem 275:14064–14069CrossRefPubMedGoogle Scholar
  69. 69.
    Vollaard NB, Shearman JP, Cooper CE (2005) Exercise-induced oxidative stress: myths, realities and physiological relevance. Sports Med 35:1045–1062CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© University of Navarra 2018

Authors and Affiliations

  1. 1.Laboratory of Exercise Biochemistry and Physiology, Graduate Program in Health Sciences, Health Sciences UnitUniversidade do Extremo Sul CatarinenseCriciúmaBrazil

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