Subscribe to RSS
DOI: 10.1055/a-2688-7735
Melatonin Attenuates Oxidative Stress After an Exercise-induced Skeletal Muscle Damage
Supported by: Fundação de Amparo à Pesquisa do Estado de São Paulo 2013/07104-6,2019/08148-3,2020/01750-7
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 301809/2022-4

Abstract
This study investigated whether, 24 hours after the exercise-induced muscle damage protocol (EIMDP), melatonin administration performed 30 minutes prior to the protocol exhibited responses about inflammatory and redox status. Control (CG), exercised (EG), and exercised+melatonin (EMG) groups were submitted to the incremental test through swimming exercise to determine the intensity of the maximal aerobic capacity (iMAC). Melatonin (10 mg kg−1) was administered, and after 30 min, the EIMDP was induced through swimming exercise (10 sets of 1 min with 30-s interval at 120% of iMAC, followed by 20 minutes continuous exercise at 100% of iMAC). The animals were euthanized 24 hours after the EIMDP. No effect on superoxide dismutase but lower activities (p<0.05) of glutathione S-transferase for EMG in relation to EG and of catalase for EMG in relation to CG were observed. EMG showed lower (p<0.05) carbonylated protein and lipid peroxidation in relation to EG and CG, respectively. Hematoxylin–eosin (HE) demonstrated higher connective tissue for EG in relation to EMG. Integrated Biomarker Responses version 2 attested the melatonin capacity in reducing antioxidant enzyme activity and muscle oxidative damage. This study demonstrated the protective role of melatonin in reducing muscle oxidative stress caused after 24 hours of the EIMDP.
Keywords
catalase - glutathione S-transferase - lipid peroxidation - carbonylated protein - swimming rats - N-acetyl-methoxytryptaminePublication History
Received: 29 October 2024
Accepted after revision: 21 August 2025
Article published online:
10 September 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1 Beck WR, Botezelli JD, Pauli JR, Ropelle ER, Gobatto CA. Melatonin has an ergogenic effect but does not prevent inflammation and damage in exhaustive exercise. Sci Rep 2015; 5: 18065
- 2 Powers SK, Deminice R, Ozdemir M, Yoshihara T, Bomkamp MP, Hyatt H. Exercise-induced oxidative stress: Friend or foe?. J Sport Health Sci 2020; 9: 415-425
- 3 Owens DJ, Twist C, Cobley JN, Howatson G, Close GL. Exercise-induced muscle damage: What is it, what causes it and what are the nutritional solutions?. Eur J Sport Sci 2019; 19: 71-85
- 4 Fu C, Xia Y, Meng F. et al. MRI Quantitative Analysis of Eccentric Exercise-induced Skeletal Muscle Injury in Rats. Acad Radiol 2020; 27: 72-79
- 5 Altinoz E, Ozmen T, Oner Z, Elbe H, Erdemli ME, Bag HG. Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats. Gen Physiol Biophys 2016; 35: 87-94
- 6 Infante NA, Faria VS, Cornachione AS, Barros Manchado-Gobatto F, Zagatto AM, Beck WR. Melatonin decreases PAX7 and CK increment after exercise-induced skeletal muscle damage. Sport Sci Health 2025; 1-11
- 7 Leite ZC, Zovico P, Rica RL. et al. Exercise-induced muscle damage after a high-intensity interval exercise session: systematic review. Int J Environ Res Public Health 2023; 20: 7082
- 8 Magherini F, Fiaschi T. et al. Oxidative stress in exercise training: the involvement of inflammation and peripheral signals. Free Radic Res 2019; 53: 1155-1165
- 9 Daruosh M, Lian-Yee K, Tengku-Fadilah TK, Saidon A. Effect of single-session aerobic exercise with varying intensities on lipid peroxidation and muscle-damage markers in sedentary males. Glob J Health Sci 2012; 4: 48
- 10 Fedorova M, Bollineni RC, Hoffmann R. Protein carbonylation as a major hallmark of oxidative damage: update of analytical strategies. Mass Spectrom Rev 2014; 33: 79-97
- 11 Gorini G, Gamberi T, Fiaschi T, Mannelli M, Modesti A, Magherini F. Irreversible plasma and muscle protein oxidation and physical exercise. Free Radic Res 2019; 53: 126-138
- 12 Kumar A, Davuluri G, Welch N. et al. Oxidative stress mediates ethanol-induced skeletal muscle mitochondrial dysfunction and dysregulated protein synthesis and autophagy. Free Radic Biol Med 2019; 145: 284-299
- 13 Beck WR, Botezelli JD, Pauli JR, Ropelle ER, Gobatto CA. Melatonin has an ergogenic effect but does not prevent inflammation and damage in exhaustive exercise. Sci Rep 2015; 5: 18065
- 14 Stacchiotti A, Favero G, Rodella LF. Impact of melatonin on skeletal muscle and exercise. Cells 2020; 9: 288
- 15 Megha KB, Arathi A, Shikha S, Alka R, Ramya P, Mohanan PV. Significance of melatonin in the regulation of circadian rhythms and disease management. Mol Neurobiol 2024; 61: 5541-5571
- 16 Faria VS, Pejon T, Gobatto CA, de Araujo GG, Cornachione AS, Beck WR. Acute melatonin administration improves exercise tolerance and the metabolic recovery after exhaustive effort. Sci Rep 2021; 11: 19228
- 17 Faria VS, Manchado-Gobatto FB, Scariot PPM, Zagatto AM, Beck WR. Melatonin Potentiates Exercise-Induced Increases in Skeletal Muscle PGC-1 α and Optimizes Glycogen Replenishment. Front Physiol 2022; 13: 803126
- 18 Liang R, Nickkholgh A, Hoffmann K. et al. Melatonin protects from hepatic reperfusion injury through inhibition of IKK and JNK pathways and modification of cell proliferation. J Pineal Res 2009; 46: 8-14
- 19 Borges LDS, Dermargos A, da Silva Junior EP, Weimann E, Lambertucci RH, Hatanaka E. Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis. J Pineal Res 2015; 58: 166-172
- 20 Kruk J, Aboul-Enein BH, Duchnik E. Exercise-induced oxidative stress and melatonin supplementation: current evidence. J Physiol Sci 2021; 71: 27
- 21 Borges LS, Dermargos A, Junior EPS, Weimann E, Lambertucci RH, Hatanaka E. Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis. J Pineal Res 2015; 58: 166-172
- 22 Canals-Garzón C, Guisado-Barrilao R, Martínez-García D, Chirosa-Ríos IJ, Jerez-Mayorga D, Guisado-Requena IM. Effect of antioxidant supplementation on markers of oxidative stress and muscle damage after strength exercise: a systematic review. Int J Environ Res Public Health 2022; 19: 1803
- 23 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
- 24 Beck W, Gobatto C. Effects of maximum intensity aerobic swimming exercise until exhaustion at different times of day on the hematological parameters in rats. Acta Physiol Hung 2013; 100: 427-434
- 25 Beck W, Scariot P, Gobatto C. Melatonin is an ergogenic aid for exhaustive aerobic exercise only during the wakefulness period. Int J Sports Med 2016; 37: 71-76
- 26 Pejon TMM, Pereira GB, de Castro CA, Anibal FF, Beck WR. Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism. Medicina 2024; 60: 740
- 27 Lima AA, Gobatto CA, Messias LHD. et al. Two water environment adaptation models enhance motor behavior and improve the success of the lactate minimum test in swimming rats. Motriz: Revista de Educação Física 2017; 23: e101607
- 28 Kregel KC, Allen DL, Booth FW. et al. Resource book for the design of animal exercise protocols. American Physiological Society; 2006. p. 152
- 29 Beck WR, Campesan YS, Gobatto CA. Validity and reliability of incremental test to determine the anaerobic threshold in swimming rats. Int J Appl Exerc Physiol 2015; 4: 25-33
- 30 American Veterinary Medical Association. AVMA Guidelines on Euthanasia. Schaumber, IL, USA: AVMA; 2013. pp. 44-45
- 31 Mccord JM, Fridovich I. Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969; 244: 6049-6055
- 32 Aebi H. Catalase in vitro. Methods Enzymol 105: 121-126 1984;
- 33 Keen JH, Habig WH, Jakoby WB. Mechanism for the several activities of the glutathione S-transferases. J Biol Chem 1976; 251: 6183-6188
- 34 Jiang ZY, Hunt JV, Wolff SP. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 1992; 202 (02) 384-389
- 35 Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Meth Enzymol 1994; 233: 357-363
- 36 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
- 37 Wick MR. The hematoxylin and eosin stain in anatomic pathology-An oftenneglected focus of quality assurance in the laboratory. Semin Diagn Pathol 2019; 36: 303-311
- 38 Sigoli E, Antão RA, Guerreiro MP. et al. Effects of low-intensity and long-term aerobic exercise on the psoas muscle of mdx mice: an experimental model of Duchenne muscular dystrophy. Int J Mol Sci 2022; 23: 4483
- 39 Sanchez W, Burgeot T, Porcher J-M. A novel “Integrated Biomarker Response” calculation based on reference deviation concept. Environ Sci Pollut Res 2013; 20: 2721-2725
- 40 Hitomi Y, Watanabe S, Kizaki T. et al. Acute exercise increases expression of extracellular superoxide dismutase in skeletal muscle and the aorta. Redox Rep 2008; 13: 213-216
- 41 He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem 2017; 44: 532-553
- 42 Rietjens SJ, Beelen M, Koopman R, Van Loon LJC, Bast A, Haenen GRMM. A single session of resistance exercise induces oxidative damage in untrained men. Med Sci Sports Exerc 2007; 39: 2145-2151
- 43 Mousavi SR, Jafari M, Rezaei S, Agha-Alinejad H, Sobhani V. Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats. Lab animal 2020; 49: 119-125
- 44 Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003; 329: 23-38
- 45 Barreiro E. Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions. Proteomes 2016; 4: 18
- 46 Mollaoglu H, Topal T, Ozler M. et al. Antioxidant effects of melatonin in rats during chronic exposure to hyperbaric oxygen. J Pineal Res 2007; 42: 50-54
- 47 Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005; 338: 668-676
- 48 Ben Dhia I, Maaloul R, Marzougui H. et al. Melatonin reduces muscle damage, inflammation and oxidative stress induced by exhaustive exercise in people with overweight/obesity. Physiol Int 2022; 109: 78-89
- 49 Erkanli K, Kayalar N, Erkanli G, Ercan F, Sener G, Kirali K. Melatonin protects against ischemia/reperfusion injury in skeletal muscle. J Pineal Res 2005; 39: 238-242
- 50 Celer M, Mogulkoc R, Baltaci AK, Dasdelen D. The effects of zinc and melatonin on muscle ischaemi-reperfusion injury in rat. Cell Mol Biol 2018; 64: 1-4
- 51 Ćirić Zdravković S, Kostić T, Marcetić ZP. et al. Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism. Can J Physiol Pharmacol 2021; 99: 360-367
- 52 Ostjen CA, Rosa CGS, Hartmann RM, Schemitt EG, Colares JR, Marroni NP. Anti-inflammatory and antioxidant effect of melatonin on recovery from muscular trauma induced in rats. Exp Mol Pathol 2019; 106: 52-59
- 53 Sokolović DT, Lilić L, Milenković V. et al. Effects of melatonin on oxidative stress parameters and pathohistological changes in rat skeletal muscle tissue following carbon tetrachloride application. Saudi Pharm J 2018; 26: 1044-1050