Open Access Open Access  Restricted Access Subscription or Fee Access

Physical exercise and oxidative stress in muscular dystrophies: is there a good balance?

L. Chico, G. Ricci, M. Cosci o Di Coscio, C. Simoncini, G. Siciliano


The effect of oxidative stress on muscle damage inducted by physical exercise is widely debated. It is generally agreed that endurance and intense exercise can increase oxidative stress and generate changes in antioxidant power inducing muscle damage; however, regular and moderate exercise can be beneficial for the health improving the antioxidant defense mechanisms in the majority of cases. Growing evidences suggest that an increased oxidative/nitrosative stress is involved in the pathogenesis of several muscular dystrophies (MDs). Notably, physical training has been considered useful for patients with these disorders. This review will focus on the involvement of oxidative stress in MDs and on the possible effects of physical activities to decrease oxidative damage and improve motor functions in MDs patients.


oxidative stress; antioxidants; regular and moderate exercise; muscular dystrophies

Full Text:



Aldehag A., Jonsson H., Lindblad J., Kottorp A., Ansved T., Kierkegaard M. Effects of hand-training in persons with myotonic dystrophy type 1--a randomized controlled cross-over pilot study. Disabil Rehabil., 35: 1798-807, 2013.

Allen D.G., Lamb G.D., Westerblad H. Skeletal muscle fatigue: cellular mechanisms. Physiol Rev., 88: 287-332, 2008.

Andersen G., Prahm K.P., Dahlqvist J.R., Citirak G., Vissing J. Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy: RCT study. Neurology. 85: 396-403, 2015.

Bankolé L.C., Millet G.Y., Temesi J., Bachasson D., Ravelojaona M., Wuyam B., Verges S., Ponsot E., Antoine J.C., Kadi F., Féasson L. Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: A randomized controlled trial. Medicine (Baltimore). 95: e4497, 2016.

Boccatonda A., Tripaldi R., Davì G., Santilli, F. Oxidative Stress Modulation Through Habitual Physical Activity. Curr Pharm Des., 22: 3648-80, 2016.

Bouzid M.A., Filaire E., McCall A., Fabre C. Radical Oxygen Species, Exercise and Aging: An Update. Sports Med., 45: 1245-61, 2015.

Brand M.D. The sites and topology of mitochondrial superoxide production. Exp Gerontol., 45: 466-72, 2010.

Çakır-Atabek H., Özdemir F., Çolak R. Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males. Biol Sport., 32, 321-8, 2015.

Castrogiovanni P. and Imbesi R. Oxidative stress and skeletal muscle in exercise. Ital J Anat Embryol., 117: 107-17, 2012.

Chalimoniuk M., Chrapusta S.J., Lukačova N., Langfort, J. Endurance training upregulates the nitric oxide/soluble guanylyl cyclase/cyclic guanosine 3',5'-monophosphate pathway in the striatum, midbrain and cerebellum of male rats. Brain Res., 1618: 29-40, 2015.

Choi M.H., Ow J.R., Yang N.D., Taneja R. Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies. Oxid Med Cell Longev., 2016.

Chung H.Y., Baek B.S., Song S.H., Kim M.S., Huh J.I., Shim K.H., Kim K.W., Lee K.H. Xanthine dehydrogenase/xanthine oxidase and oxidative stress. Age (Omaha), 20, 127-40, 1997.

Cipak Gasparovic A., Zarkovic N., Zarkovic K., Semen K., Kaminskyy D., Yelisyeyeva O., Bottari S.P. Biomarkers of oxidative and nitro-oxidative stress: conventional and novel approaches. Br J Pharmacol., 2016.

Dahlqvist J.R. and Vissing J. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders. J Mol Neurosci., 58: 388-93, 2016.

Darras B.T., Miller D.T., Urion D.K. Dystrophinopathies. [updated 2014 Nov 26], 2000. In: Pagon R.A., Adam M.P., Ardinger H.H., Wallace S.E., Amemiya A., Bean L.J.H., Bird T.D., Fong C.T., Mefford H.C., Smith R.J.H., Stephens K., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington Seattle, 1993-2016.

Davies K.E. and Nowak K. J. Molecular mechanisms of muscular dystrophies: old and new players. Nature Reviews Molecular Cell Biology. 7: 762–773, 2006.

Dmitriev P., Bou Saada Y., Dib C., Ansseau E., Barat A., Hamade A., Dessen P., Robert T., Lazar V., Louzada R.A., Dupuy C., Zakharova V., Carnac G., Lipinski M., Vassetzky Y.S. DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients. Free Radic Biol Med., 99: 244-258, 2016.

Ensrud E. and Kissel J.T. Aerobic exercise in muscular dystrophy: gain without pain. Neurology. 85: 392-3, 2015.

Ervasti J. M. and Campbell K. P. Membrane organization of the dystrophin-glycoprotein complex. Cell, 66: 1121–1131, 1991.

Falone S., Mirabilio A., Pennelli A., Cacchio M., Di Baldassarre A., Gallina S., Passerini A., Amicarelli F. Differential impact of acute bout of exercise on redox- and oxidative damage-related profiles between untrained subjects and amateur runners. Physiol Res., 59: 953-61, 2010.

Farinha J.B., Steckling F.M., Stefanello S.T., Cardoso M.S., Nunes L.S., Barcelos R.P., Duarte T., Kretzmann N.A., Mota C.B., Bresciani G., Moresco R.N., Duarte M.M., Dos Santos D.L., Soares F.A. Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome. Sports Med Open., 1: 3, 2015.

Fisher-Wellman K. and Bloomer R.J. Acute exercise and oxidative stress: a 30 year history. Dyn Med., 8: 1, 2009.

Fontana S., Schillaci O., Frinchi M., Giallombardo M., Morici G., Di Liberto V., Alessandro R., De Leo G., Perciavalle V., Belluardo N., Mudò G. Reduction in mdx mouse muscle degeneration by low-intensity endurance exercise: a protomi analysis in quadriceps muscle of exercised compared with sedentary mdx mice. Biosci Rep., 35. pii: e00213, 2015.

Frijhoff J., Winyard P.G., Zarkovic N., Davies S.S., Stocker R., Cheng D., Knight A.R., Taylor E.L., Oettrich, J., Ruskovska T., Gasparovic A.C., Cuadrado A., Weber D., Poulsen H.E., Grune T., Schmidt H.H., Ghezzi P. Clinical Relevance of Biomarkers of Oxidative Stress. Antioxid Redox Signal., 23: 1144-70, 2015.

Gatica L.V. and Rosa A.L. A complex interplay of genetic and epigenetic events leads to abnormal expression of the DUX4 gene in facioscapulohumeral muscular

dystrophy. Neuromuscul Disord., 26:844-852, 2016.

Giorgio M., Trinei M., Migliaccio E., Pelicci P.G. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol., 8: 722-8, 2007.

Gomez-Cabrera M.C., Domenech E., Viña J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med., 44: 126-31, 2008.

Goncalves R.L., Quinlan C.L., Perevoshchikova I.V., Hey-Mogensen, M., Brand M.D. Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. J Biol Chem., 290: 209-27, 2015.

Grozdanovic Z., Christova T., Gosztonyi G., Mellerowicz H., Blottner D., Grossran R. Absence of nitric oxide synthase I despite the presence of the dystrophin complex in human striated muscle. Histochem J., 97-104, 1997.

Gücüyener K., Ergenekon E., Erbas D., Pinarli G., Serdaroğlu A. The serum nitric oxide levels in patients with Duchenne muscular dystrophy. Brain Dev., 22: 181-3, 2000.

Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans., 35: 1147-50, 2007.

He F., Li J., Liu Z., Chuang C.C., Yang W., Zuo L. Redox Mechanism of Reactive Oxygen Species in Exercise. Front Physiol., 7: 486, 2016.

Heydemann A. and McNally E. NO more muscle fatigue. J Clin Invest., 119: 448-50, 2009.

Hyzewicz J., Tanihata J., Kuraoka M., Ito N., Miyagoe-Suzuki Y., Takeda S. Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction. Free Radic Biol Med., 82: 122-36, 2015.

Jansen M., van Alfen N., Geurts AC., de Groot I.J. Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial "no use is disuse". Neurorehabil Neural Repair., 27: 816-27, 2013.

Judge A.R. and Dodd S.L. Oxidative damage to skeletal muscle following an acute bout of contractile claudication. Atherosclerosis, 171: 219-24, 2003.

Kaczor J.J., Hall J.E., Payne E., Tarnopolsky M.A. Low intensity training decreases markers of oxidative stress in skeletal muscle of mdx mice. Free Radic Biol Med., 43: 145-54, 2007.

Kar N.C. and Pearson C.M. Catalase superoxide dismutase glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle. Clin Chim Acta., 94: 277-80, 1979.

Kocabaş R., Namiduru E.S., Bagçeci A.M., Erenler A.K., Karakoç Ö., Örkmez M., Akan M., Erdemli H.K., Taysi S., Tarakçioglu M. The acute effects of interval exercise on oxidative stress and antioxidant status in volleyball players. J Sports Med Phys Fitness. [Epub ahead of print], 2016.

Kumar A., Kumar V., Singh S.K., Muthuswamy S., Agarwal S. Imbalanced oxidant and antioxidant ratio in myotonic dystrophy type 1. Free Radic Res., 48: 503-10, 2014.

Kurutas E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J., 15: 71, 2016.

Kuwahara H., Horie T., Ishikawa S., Tsuda C., Kawakami S., Noda Y., Kaneko T., Tahara S., Tachibana T., Okabe M., Melki J., Takano R., Toda T., Morikawa D., Nojiri H., Kurosawa H., Shirasawa T., Shimizu, T. Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy. Free Radic Biol Med., 48: 1252-62, 2010.

Lamb G.D. and Westerblad H. Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscle. J Physiol., 589: 2119-27, 2011.

Lattanzi G., Marmiroli S., Facchini A., Maraldi N.M. Nuclear damages and oxidative stress: new perspectives for laminopathies. Eur J Histochem. 56: e45, 2012. doi:10.4081/ejh.2012.e45.

Lemmers R.J., Goeman J.J., van der Vliet P.J., van Nieuwenhuizen M.P., Balog J., Vos-Versteeg M., Camano P., Ramos Arroyo M.A., Jerico I., Rogers M.T., Miller D.G., Upadhyaya M., Verschuuren J.J., Lopez de Munain Arregui A., van Engelen B.G., Padberg G.W., Sacconi S., Tawil R., Tapscott S.J., Bakker B., van der Maarel S.M. Inter-individual differences in CpG methylation at D4Z4 correlate with clinical variability in FSHD1 and FSHD2. Hum Mol Genet., 24: 659-69, 2015.

Mangge H., Becker K., Fuchs D., Gostner J.M. Antioxidants, inflammation and cardiovascular disease. World J Cardiol., 6: 462-77, 2014.

Nikolić-Kokić A., Marinković D., Perić S., Stević Z., Spasić M.B., Blagojević D., Rakocˇević-Stojanović V. Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients. Redox Rep., 21: 232-7, 2016.

Olsen D.B., Ørngreen M.C., Vissing J. Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy. Neurology. 64: 1064-6, 2005.

Orngreen M.C., Olsen D.B., Vissing J. Aerobic training in patients with myotonic dystrophy type 1. Ann Neurol. 2005 57 754-7. PubMed PMID: 15852373.

Oztasan N., Taysi S., Gumustekin K., Altinkaynak K., Aktas O., Timur H., Siktar E., Keles S., Akar S., Akcay F., Dane S., Gul M. Endurance training attenuates exercise-induced oxidative stress in erythrocytes in rat. Eur J Appl Physiol., 91: 622-7, 2004.

Pacher P., Beckman J.S., Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev., 87: 315-424, 2007.

Pantic B., Trevisan E., Citta A., Rigobello M.P., Marin O., Bernardi P., Salvatori S., Rasola A. Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by assembling a hexokinase II-Src complex on the mitochondrial surface. Cell Death Dis., 4: e858, 2013.

Pendyala S. and Natarajan V. Redox regulation of Nox proteins. Respir Physiol Neurobiol., 174: 265-71, 2010.

Pingitore A., Lima G.P., Mastorci F., Quinones A., Iervasi G., Vassalle C. Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports. Nutrition., 31: 916-22, 2015.

Pisoschi A.M. and Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem., 97: 55-74, 2015.

Powers S.K. and Jackson M.J. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev., 88: 1243-76, 2008.

Ragusa R.J., Chow C.K., Porter J.D. Oxidative stress as a potential pathogenic mechanism in an animal model of Duchenne muscular dystrophy. Neuromuscul Disord., 7: 379-86, 1997.

Rajakumar D., Alexander M., Oommen A. Oxidative stress NF-κB and the ubiquitin proteasomal pathway in the pathology of calpainopathy. Neurochem Res. 38: 2009-18, 2013.

Rajakumar D., Senguttuvan S., Alexander M., Oommen A. Involvement of oxidative stress nuclear factor kappa B and the ubiquitin proteasomal pathway in dysferlinopathy. Life Sci., 108: 54-61, 2014.

Rando T.A. Role of nitric oxide in the pathogenesis of muscular dystrophies: a ‘two hit’ hypothesis of the cause of muscle necrosis. Microscopy Research and Technique. 55: 223–235, 2001.

Rando T.A., Disatnik M.H., Yu Y., Franco A. Muscle cells from mdx mice have an increased susceptibility to oxidative stress. Neuromuscul Disord., 8: 14-21, 1998.

Reid M.B. Free radicals and muscle fatigue: Of ROS, canaries, and the IOC. Free Radic Biol Med., 44: 169-79, 2008.

Ricci G., Scionti I., Sera F., Govi M., D'Amico R., Frambolli I., Mele F., Filosto M., Vercelli L., Ruggiero L., Berardinelli A., Angelini C., Antonini G., Bucci E., Cao M., Daolio J., Di Muzio A., Di Leo R., Galluzzi G., Iannaccone E., Maggi L., Maruotti V., Moggio M., Mongini T., Morandi L., Nikolic A., Pastorello E., Ricci E., Rodolico C., Santoro L., Servida M., Siciliano G., Tomelleri G., Tupler R. Large scale genotype-phenotype analyses indicate that novel prognostic tools are required for families with facioscapulohumeral muscular dystrophy. Brain. 136: 3408-17, 2013.

Ricci G., Zatz M., Tupler R. Facioscapulohumeral muscular dystrophy: more complex than it appears. Curr Mol Med., 2014. [Epub ahead of print].

Rodriguez M.C. and Tarnopolsky M.A. Patients with dystrophinopathy show evidence of increased oxidative stress. Free Radic Biol Med., 34: 1217-20, 2003.

Ryan M.J., Jackson J.R., Hao Y., Leonard, S.S., Always S.E. Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice. Free Radic Biol Med., 51: 38-52, 2011.

Schieber M. and Chande N.S. ROS function in redox signaling and oxidative stress. Curr Biol., 24: R453-62, 2014.

Schill K.E., Altenberger A.R., Lowe J., Periasamy M., Villamena F.A., Rafael-Fortney J.A., Devor S.T. Muscle damage metabolism and oxidative stress in mdx mice: Impact of aerobic running. Muscle Nerve. 54: 110-7, 2016.

Seifi-Skishahr F., Damirchi A., Farjaminezhad M., Babaei P. Physical Training Status Determines Oxidative Stress and Redox Changes in Response to an Acute Aerobic Exercise. Biochem Res Int., 3757623, 2016.

Selsby T.J. “Increased catalase expression improves muscle function in mdx mice” Experimental Physiology. 96 194–202, 2011.

Shin J., Tajrishi M.M., Ogura Y., Kumar A. Wasting mechanisms in muscular dystrophy. Int J Biochem Cell Biol., 45: 2266-79, 2013.

Siciliano G., Pasquali L., Rocchi A., Falorni M., Galluzzi F., Rocco A., Malvaldi G., Pompella A., Paolicchi A. Advanced oxidation protein products in serum of patients with myotonic disease type I: association with serum gamma-glutamyltransferase and disease severity. Clin Chem Lab Med., 43: 745-7, 2005.

Siciliano G., Simoncini C., Giannotti S., Zampa V., Angelini C., Ricci G. Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages. Acta Myol., 34: 3-8, 2015.

Sieprath T., Corne T.D., Nooteboom M., Grootaert C., Rajkovic A., Buysschaert B., Robijns J., Broers J.L. Ramaekers F.C., Koopman W.J., Willems P.H., De Vos W.H. Sustained accumulation of prelamin A and depletion of lamin A/C both cause oxidative stress and mitochondrial dysfunction but induce different cell fates. Nucleus. 6: 236-46, 2015.

Stamler J.S. and Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev., 81: 209-237, 2001.

Steinbacher P. and Eckl P. Impact of oxidative stress on exercising skeletal muscle. Biomolecules, 5: 356-77, 2015.

Sveen M.L., Andersen S.P., Ingelsrud L.H., Blichter S., Olsen N.E., Jønck S., Krag T.O., Vissing J. Resistance training in patients with limb-girdle and becker muscular dystrophies. Muscle Nerve. 47: 163-9, 2013.

Sveen M.L., Jeppesen T.D., Hauerslev S., Køber L., Krag T.O., Vissing J. Endurance training improves fitness and strength in patients with Becker muscular dystrophy. Brain. 131: 2824-31, 2008.

Sveen M.L., Jeppesen T.D., Hauerslev S., Krag T.O., Vissing J. Endurance training: an effective and safe treatment for patients with LGMD2I. Neurology. 68: 59-61, 2007.

Tidball J.G. and Wehling-Henricks M. Expression of a NOS transgene in dystrophin-deficient muscle reduces muscle membrane damage without increasing the expression of membrane-associated cytoskeletal proteins. Mol Genet Metab., 82: 312-20, 2004.

Tramonti C., Dalise S., Bertolucci F., Rossi B., Chisari C. Abnormal Lactate Levels Affect Motor Performance in Myotonic Dystrophy Type 1. Eur J Transl Myol., 24: 4726, 2014.

Turki A., Hayot M., Carnac G., Pillard F., Passerieux E., Bommart S., Raynaud de Mauverger E., Hugon G., Pincemail J., Pietri S., Lambert K., Belayew A., Vassetzky Y., Juntas Morales R., Mercier J., Laoudj-Chenivesse D. Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction. Free Radic Biol Med., 53: 1068-79, 2012.

Usuki F. and Ishiura S. Expanded CTG repeats in myotonin protein kinase increase susceptibility to oxidative stress. Neuroreport., 9: 2291-6, 1998.

Usuki F., Takahashi N., Sasagawa N., Ishiura S. Differential signaling pathways following oxidative stress in mutant myotonin protein kinase cDNA-transfected C2C12 cell lines. Biochem Biophys Res Commun., 267: 739-43, 2000.

Vincent A.E., Rosa H.S., Alston C.L., Grady J.P., Rygiel K.A., Rocha M.C., Barresi R., Taylor R.W., Turnbull D.M. Dysferlin mutations and mitochondrial dysfunction. Neuromuscul Disord., 26: 782-788, 2016.

Vissing C.R., Preisler N., Husu E., Prahm K.P., Vissing J. Aerobic training in patients with anoctamin 5 myopathy and hyperckemia. Muscle Nerve. 50: 119-23, 2014.

Voet N., Bleijenberg G., Hendriks J., de Groot I., Padberg G., van Engelen B., Geurts A. Both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue in FSHD: an RCT. Neurology. 83: 1914-22, 2014.

Wang X. and Robinson P.J. Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J Neurochem., 68: 443-56, 1997.

Wehling M., Spencer M.J., Tidball J.G. A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J Cell Biol., 155: 123-31, 2001.

Westerblad H. and Allen D.G. Emerging roles of ROS/RNS in muscle function and fatigue. Antioxid Redox Signal., 15: 2487-99, 2011.


  • There are currently no refbacks.