Abstract
Skeletal muscle can be ultrastructurally damaged by eccentric exercise, and the damage causes metabolic disruption in muscle. This study aimed to determine changes in the metabolomic patterns in urine and metabolomic markers in muscle damage after eccentric exercise. Five men and 6 women aged 19∼23 years performed 30 min of the bench step exercise at 70 steps per min at a determined step height of 110% of the lower leg length, and stepping frequency at 15 cycles per min. 1H NMR spectral analysis was performed in urine collected from all participants before and after eccentric exercise-induced muscle damage conventionally determined using a visual analogue scale (VAS) and maximal voluntary contraction (MVC). Urinary metabolic profiles were built by multivariate analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) using SIMCA-P. From the OPLS-DA, men and women were separated 2 hr after the eccentric exercise and the separated patterns were maintained or clarified until 96 hr after the eccentric exercise. Subsequently, urinary metabolic profiles showed distinct trajectory patterns between men and women. Finally, we found increased urinary metabolites (men: alanine, asparagine, citrate, creatine phosphate, ethanol, formate, glucose, glycine, histidine, and lactate; women: adenine) after the eccentric exercise. These results could contribute to understanding metabolic responses following eccentric exercise-induced muscle damage in humans.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
REFERENCES
Stauber, W.T. (1989) Eccentric action of muscles: physiology, injury, and adaptation. Exerc. Sport Sci. Rev., 17, 157–185.
Brown, S., Day, S. and Donnelly, A. (1999) Indirect evidence of human skeletal muscle damage and collagen breakdown after eccentric muscle actions. J. Sports Sci., 17, 397–402.
Woledge, R.C., Curtin, N.A. and Homsher, E. (1985) Energetic aspects of muscle contraction. Monogr. Physiol. Soc., 41, 1–357.
Bigland-Ritchie, B. and Woods, J.J. (1974) Integrated EMG and oxygen uptake during dynamic contractions of human muscles. J. Appl. Physiol., 36, 475–479.
McCully, K.K. and Faulkner, J.A. (1986) Characteristics of lengthening contractions associated with injury to skeletal muscle fibers. J. Appl. Physiol., 61, 293–299.
Tee, J.C., Bosch, A.N. and Lambert, M.I. (2007) Metabolic consequences of exercise-induced muscle damage. Sports Med., 37, 827–836.
Byrne, C., Twist, C. and Eston, R. (2004) Neuromuscular function after exercise-induced muscle damage: theoretical and applied implications. Sports Med., 34, 49–69.
Asp, S., Daugaard, J.R. and Richter, E.A. (1995) Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal muscle. J. Physiol., 482, 705–712.
Asp, S., Rohde, T. and Richter, E.A. (1997) Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content. J. Appl. Physiol., 83, 1482–1485.
Asp, S., Daugaard, J.R., Kristiansen, S., Kiens, B., Richter, E.A. (1998) Exercise metabolism in human skeletal muscle exposed to prior eccentric exercise. J. Physiol., 509, 305–313.
Asp, S., Daugaard, J.R., Rohde, T., Adamo, K. and Graham, T. (1999) Muscle glycogen accumulation after a marathon: roles of fiber type and pro- and macroglycogen. J. Appl. Physiol., 86, 474–478.
Costill, D.L., Pascoe, D.D., Fink, W.J., Robergs, R.A., Barr, S.I. and Pearson, D. (1990) Impaired muscle glycogen resynthesis after eccentric exercise. J. Appl. Physiol., 69, 46–50.
Evans, W.J., Meredith, C.N., Cannon, J.G., Dinarello, C.A., Frontera, W.R., Hughes, V.A., Jones, B.H. and Knuttgen, H.G. (1986) Metabolic changes following eccentric exercise in trained and untrained men. J. Appl. Physiol., 61, 1864–1868.
Kirwan, J.P., Hickner, R.C., Yarasheski, K.E., Kohrt, W.M., Wiethop, B.V. and Holloszy, J.O. (1992) Eccentric exercise induces transient insulin resistance in healthy individuals. J. Appl. Physiol., 72, 2197–2202.
Nosaka, K. and Clarkson, P.M. (1995) Muscle damage following repeated bouts of high force eccentric exercise. Med. Sci. Sports Exerc., 27, 1263–1269.
Selkow, N.M., Day, C., Liu, Z., Hart, J.M., Hertel, J. and Saliba, S.A. (2012) Microvascular perfusion and intramuscular temperature of the calf during cooling. Med. Sci. Sports Exerc., 44, 850–856.
Semark, A., Noakes, T.D., St Clair, G.A. and Lambert, M.I. (1999) The effect of a prophylactic dose of flurbiprofen on muscle soreness and sprinting performance in trained subjects. J. Sports Sci., 17, 197–203.
Sorichter, S., Puschendorf, B. and Mair, J. (1999) Skeletal muscle injury induced by eccentric muscle action: muscle proteins as markers of muscle fiber injury. Exerc. Immunol. Rev., 5, 5–21.
Tuominen, J.A., Ebeling, P., Bourey, R., Koranyi, L., Lamminen, A., Rapola, J., Sane, T., Vuorinen-Markkola, H. and Koivisto, V.A. (1996) Postmarathon paradox: insulin resistance in the face of glycogen depletion. Am. J. Physiol., 270, E336–E343.
Brancaccio, P., Lippi, G. and Maffulli, N. (2010) Biochemical markers of muscular damage. Clin. Chem. Lab. Med., 48, 757–767.
Miles, M.P., Andring, J.M., Pearson, S.D., Gordon, L.K., Kasper, C., Depner, C.M. and Kidd, J.R. (2008) Diurnal variation, response to eccentric exercise, and association of inflammatory mediators with muscle damage variables. J. Appl. Physiol., 104, 451–458.
Oosterom, D.L. and Betjes, M.G. (2006) Exertion-related abnormalities in the urine. Ned. Tijdschr. Geneeskd., 150, 606–610.
Chung, Y.L., Rider, L.G., Bell, J.D., Summers, R.M., Zemel, L.S., Rennebohm, R.M., Passo, M.H., Hicks, J., Miller, F.W. and Scott, D.L. (2005) Juvenile dermatomyositis disease activity collaborative study G. Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. Arthritis Rheum., 53, 565–570.
Huerta-Alardin, A.L., Varon, J. and Marik, P.E. (2005) Bench-to-bedside review: rhabdomyolysis -- an overview for clinicians. Crit. Care, 9, 158–169.
Khan, F.Y. (2009) Rhabdomyolysis: a review of the literature. Neth. J. Med., 67, 272–283.
Duchen, M.R., Valdeolmillos, M., O’Neill, S.C. and Eisner, D.A. (1990) Effects of metabolic blockade on the regulation of intracellular calcium in dissociated mouse sensory neurones. J. Physiol., 424, 411–426.
Duncan, C.J. (1987) Role of calcium in triggering rapid ultrastructural damage in muscle: a study with chemically skinned fibres. J. Cell Sci., 87, 581–594.
Armstrong, R.B., Warren, G.L. and Warren, J.A. (1991) Mechanisms of exercise-induced muscle fibre injury. Sports Med., 12, 184–207.
Busch, W.A., Stromer, M.H., Goll, D.E. and Suzuki, A. (1972) Ca2+-specific removal of Z lines from rabbit skeletal muscle. J. Cell Biol., 52, 367–381.
Baird, M.F., Graham, S.M., Baker, J.S. and Bickerstaff, G.F. (2012) Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J. Nutr. Metab., 2012, 960363.
Barding, G.A., Jr., Salditos, R. and Larive, C.K. (2012) Quantitative NMR for bioanalysis and metabolomics. Anal. Bioanal. Chem., 404, 1165–1179.
Jordan, K.W., Nordenstam, J., Lauwers, G.Y., Rothenberger, D.A., Alavi, K., Garwood, M. and Cheng, L.L. (2009) Metabolomic characterization of human rectal adenocarcinoma with intact tissue magnetic resonance spectroscopy. Dis. Colon. Rectum., 52, 520–525.
Ra, S.G., Maeda, S., Higashino, R., Imai, T. and Miyakawa, S. (2014) Metabolomics of salivary fatigue markers in soccer players after consecutive games. Appl. Physiol. Nutr. Metab., 39, 1120–1126.
Hicks, K.M., Onambele, G.L., Winwood, K. and Morse, C.I. (2016) Muscle damage following maximal eccentric knee extensions in males and females. PLoS ONE, 11, e0150848.
Newham, D.J., Jones, D.A. and Edwards, R.H. (1983) Large delayed plasma creatine kinase changes after stepping exercise. Muscle Nerve, 6, 380–385.
Vissing, K., Overgaard, K., Nedergaard, A., Fredsted, A. and Schjerling, P. (2008) Effects of concentric and repeated eccentric exercise on muscle damage and calpain-calpastatin gene expression in human skeletal muscle. Eur. J. Appl. Physiol., 103, 323–332.
Wilson, J.M., Kim, J.S., Lee, S.R., Rathmacher, J.A., Dalmau, B., Kingsley, J.D., Koch, H., Manninen, A.H., Saadat, R. and Panton, L.B. (2009) Acute and timing effects of betahydroxybeta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage. Nutr. Metab. (Lond), 6, 6.
Baroni, B.M., Leal Junior, E.C., De Marchi, T., Lopes, A.L., Salvador, M. and Vaz, M.A. (2010) Low level laser therapy before eccentric exercise reduces muscle damage markers in humans. Eur. J. Appl. Physiol., 110, 789–796.
Selkow, N.M., Herman, D.C., Liu, Z., Hertel, J., Hart, J.M. and Saliba, S.A. (2015) Blood flow after exercise-induced muscle damage. J. Athl. Train, 50, 400–406.
Twist, C. and Eston, R.G. (2009) The effect of exercise-induced muscle damage on perceived exertion and cycling endurance performance. Eur. J. Appl. Physiol., 105, 559–567.
Chen, T.C., Lin, K.Y., Chen, H.L., Lin, M.J. and Nosaka, K. (2011) Comparison in eccentric exercise-induced muscle damage among four limb muscles. Eur. J. Appl. Physiol., 111, 211–223.
Penailillo, L., Blazevich, A., Numazawa, H. and Nosaka, K. (2015) Rate of force development as a measure of muscle damage. Scand. J. Med. Sci. Sports, 25, 417–427.
Clarkson, P.M. and Hubal, M.J. (2002) Exercise-induced muscle damage in humans. Am. J. Phys. Med. Rehabil., 81, S52–S69.
Rinard, J., Clarkson, P.M., Smith, L.L. and Grossman, M. (2000) Response of males and females to high-force eccentric exercise. J. Sports Sci., 18, 229–236.
Ruoppolo, M., Scolamiero, E., Caterino, M., Mirisola, V., Franconi, F. and Campesi, I. (2015) Female and male human babies have distinct blood metabolomic patterns. Mol. Biosyst., 11, 2483–2492.
Tso, V.K., Sydora, B.C., Foshaug, R.R., Churchill, T.A., Doyle, J., Slupsky, C.M. and Fedorak, R.N. (2013) Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease. PLoS ONE, 8, e67654.
Dieli-Conwright, C.M., Spektor, T.M., Rice, J.C., Sattler, F.R. and Schroeder, E.T. (2009) Hormone therapy attenuates exercise-induced skeletal muscle damage in postmenopausal women. J. Appl. Physiol., 107, 853–858.
Saks, V. (2008) The phosphocreatine-creatine kinase system helps to shape muscle cells and keep them healthy and alive. J. Physiol., 586, 2817–2818.
Vigelso, A., Andersen, N.B. and Dela, F. (2014) The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training. Int. J. Physiol. Pathophysiol. Pharmacol., 6, 84–101.
Koopman, R., Ly, C.H. and Ryall, J.G. (2014) A metabolic link to skeletal muscle wasting and regeneration. Front Physiol., 5, 32.
Powers, S.K. and Jackson, M.J. (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol. Rev., 88, 1243–1276.
Reid, M.B., Shoji, T., Moody, M.R. and Entman, M.L. (1992) Reactive oxygen in skeletal muscle. II. Extracellular release of free radicals. J. Appl. Physiol., 73, 1805–1809.
Son, D.O., Satsu, H. and Shimizu, M. (2005) Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells. FEBS Lett., 579, 4671–4677.
Tidball, J.G. (2005) Inflammatory processes in muscle injury and repair. Am. J. Physiol. Regul. Integr. Comp. Physiol., 288, R345–R353.
Mangino, M.J., Murphy, M.K., Grabau, G.G. and Anderson, C.B. (1991) Protective effects of glycine during hypothermic renal ischemia-reperfusion injury. Am. J. Physiol., 261, F841–F848.
Rush, G.F. and Ponsler, G.D. (1991) Cephaloridine-induced biochemical changes and cytotoxicity in suspensions of rabbit isolated proximal tubules. Toxicol. Appl. Pharmacol., 109, 314–326.
Ascher, E., Hanson, J.N., Cheng, W., Hingorani, A. and Scheinman, M. (2001) Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury. Surgery, 129, 231–235.
Ham, D.J., Murphy, K.T., Chee, A., Lynch, G.S. and Koopman, R. (2014) Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clin. Nutr., 33, 448–458.
Becker, A., Fritz-Wolf, K., Kabsch, W., Knappe, J., Schultz, S. and Volker Wagner, A.F. (1999) Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase. Nat. Struct. Biol., 6, 969–975.
Dashko, S., Zhou, N., Compagno, C. and Piskur, J. (2014) Why, when, and how did yeast evolve alcoholic fermentation? FEMS Yeast Res., 14, 826–832.
Doi, Y. and Ikegami, Y. (2014) Pyruvate formate-lyase is essential for fumarate-independent anaerobic glycerol utilization in the Enterococcus faecalis strain W11. J. Bacteriol., 196, 2472–2480.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Jang, HJ., Lee, J.D., Jeon, HS. et al. Metabolic Profiling of Eccentric Exercise-Induced Muscle Damage in Human Urine. Toxicol Res. 34, 199–210 (2018). https://doi.org/10.5487/TR.2018.34.3.199
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.5487/TR.2018.34.3.199