Purpose This study investigated the time-dependent effects of melatonin administration on recovery following physical exercise, focusing on key tissues involved in energy metabolism and serum markers of skeletal muscle damage.
Methods Sixty male Wistar rats were subjected to a 60-min swimming session at 90% of the maximal aerobic capacity and then received melatonin (10 mg/kg) or vehicle, being euthanized at 6, 12 or 48 h post-exercise. Data were analyzed using two-way ANOVA with post hoc tests. Effect sizes and multivariate approaches (Integrated Biomarker Response (IBR) and Principal Component Analysis (PCA)) were applied to assess treatment and time effects.
Results Melatonin significantly enhanced glycogen resynthesis in the soleus, red and white gastrocnemius, gluteus maximus, and liver (P < 0.01), and concurrently reduced triglyceride content in the soleus, white gastrocnemius, gluteus maximus, and liver (P < 0.01). Serum glucose, triglyceride, creatine kinase (CK), and lactate dehydrogenase (LDH) levels were significantly attenuated in melatonin-treated animals, indicating reduced muscle damage. IBR analysis revealed the most pronounced metabolic modulation at 12 h post-exercise, while PCA showed distinct clustering of melatonin-treated groups, particularly at 6 h, supporting a temporally dynamic effect.
Conclusion These findings suggest that melatonin improved substrate restoration and enhanced metabolic recovery in a tissue and time-specific manner, likely through mechanisms involving improved glucose uptake, lipid oxidation, and protection against skeletal muscle damage induced by exercise.
| [1] |
Ahmad SB, Ali A, Bilal M, Rashid SM, Wani AB, Bhat RR, et al. Melatonin and health: insights of melatonin action, biological functions, and associated disorders. Cell Mol Neurobiol, 2023, 436243758.
|
| [2] |
Jia M, Luo A, Wei M, Zhang Y, Wu T, Chen N. Melatonin: beyond circadian regulation - exploring its diverse physiological roles and therapeutic potential. Sleep Med Rev, 2025, 82: 102123.
|
| [3] |
Kołodziejska R, Woźniak A, Bilski R, Wesołowski R, Kupczyk D, Porzych M, et al. Melatonin—A powerful antioxidant in neurodegenerative diseases. Antioxid (Basel Switzerland), 2025, 147819.
|
| [4] |
de Faria VS, Pejon TMM, Gobatto CA, Araujo GG, Cornachione AS, Beck WR. Acute melatonin administration improves exercise tolerance and the metabolic recovery after exhaustive effort. Sci Rep, 2021, 11119228.
|
| [5] |
Faria VS, Manchado-Gobatto FB, Scariot PPM, Zagatto AM, Beck WR. Melatonin potentiates exercise-induced increases in skeletal muscle PGC-1α and optimizes lycogen replenishment. Front Physiol, 2022, 13: 803126.
|
| [6] |
Berzosa C, Bascuas PJ, Piedrafita E. Effects of melatonin administration on physical performance and biochemical responses following exhaustive treadmill exercise. Curr Issues Mol Biol, 2024, 46121364761.
|
| [7] |
Cipriano AE, Silva AA, Porcari M, Messias A, Bertolucci LH, Beck WR. Effect of acute administration of melatonin immediately after physical exercise on the amino acid profile of rat’s skeletal muscle and liver. Metabolomics, 2025, 215129.
|
| [8] |
Ciałowicz M, Woźniewski M, Murawska-Ciałowicz E, Dzięgiel P. The influence of irisin on selected organs—the liver, kidneys, and lungs: the role of physical exercise. Cells, 2025, 14161228.
|
| [9] |
Bessa AL, Oliveira VN, Agostini GG, Oliveira RJ, Oliveira AC, White GE, et al. Exercise intensity and recovery: biomarkers of injury, inflammation, and oxidative stress. J Strength Cond Res, 2016, 3023119.
|
| [10] |
Lopes M, Marques MC, Fonseca N, Marques DL, Nunes C, Marinho DA, et al. Effects of eight- week single- set resistance training on muscle health, metabolic profile and oxidative stress in individuals with cognitive impairment. Appl Sci, 2025, 15137091.
|
| [11] |
Cho JH, Bhutani S, Kim CH, Irwin MR. Anti-inflammatory effects of melatonin: a systematic review and meta-analysis of clinical trials. Brain Behav Immun, 2021, 93: 245-53.
|
| [12] |
Kruk J, Aboul-Enein BH, Duchnik E. Exercise-induced oxidative stress and melatonin supplementation: current evidence. J Physiol Sci, 2021, 71127.
|
| [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, 5118065.
|
| [14] |
Beck WR, Scariot PPM, Gobatto CA. Melatonin is an ergogenic aid for exhaustive aerobic exercise only during the wakefulness period. Int J Sports Med, 2016, 371716.
|
| [15] |
Luttrell MJ, Halliwill JR. Recovery from exercise: vulnerable state, window of opportunity, or crystal ball?. Front Physiol, 2015, 6: 204.
|
| [16] |
Párraga-Montilla JA, García-Ramos A, Castaño-Zambudio A, Capelo-Ramírez F, González-Hernández JM, Cordero-Rodríguez Y, et al. Acute and delayed effects of a resistance training session leading to muscular failure on mechanical, metabolic, and perceptual responses. J Strength Cond Res, 2020, 34822206.
|
| [17] |
Peake JM. Recovery after exercise: what is the current state of play?. Curr Opin Physiol, 2019, 1011726.
|
| [18] |
Momesso Santos CM, Amaral JB, Rossi M, Vieria RP, Abad CCC, Bachi ALL. Metabolic and immune/inflammatory alterations induced by a triathlon under extreme conditions. Front sports Act living, 2022, 4: 915343.
|
| [19] |
Pendergrast LA, Lundell LS, Ehrlich AM, Ashcroft SP, Schönke M, Basse AL, et al. Time of day determines postexercise metabolism in mouse adipose tissue. Proc Natl Acad Sci, 2023, 1208e2218510120.
|
| [20] |
Senna GW, Dantas EHM, Scudese E, Brandão PP, Lira VA, Baffi M, et al. Higher muscle damage triggered by shorter inter-set rest periods in volume-equated resistance exercise. Front Physiol, 2022, 13: 827847.
|
| [21] |
Kregel KC, Allen DL, Booth FW, Fleshner MR, Hendiksen EJ, Musch TL, et al. Resource book for the design of animal exercise protocols. Rockville, MD, USA: American Physiological Society; 2006.
|
| [22] |
Beck WR, Campesan YS, Gobatto CA. Validity and reliability of swimming incremental test to estimate maximum aerobic capacity of rats. Med Sci Sports Exerc, 2015, 46S19423.
|
| [23] |
Engel PC, Jones JB. Causes and elimination of erratic blanks in enzymatic metabolite assays involving the use of NAD + in alkaline hydrazine buffers: Improved conditions for the assay of l-glutamate, l-lactate, and other metabolites. Anal Biochem, 1978, 88247584.
|
| [24] |
Association AVM. AVMA guidelines for the euthanasia of animals: 2020 Edition. Schaumburg, IL: American Veterinary Medical Association; 2020.
|
| [25] |
DuBois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem, 1956, 28335056.
|
| [26] |
COHEN J. Statistical power analysis for the behavioral sciences, 19882Hillsdale, NJLawrence Erlbaum Associates
|
| [27] |
Beliaeff B, Burgeot T Integrated biomarker response: a useful tool for ecological risk assessment. Environ Toxicol Chem. 2002;21(6):1316–22. https://doi.org/10.1897/1551-5028(2002)021%3C1316:ibraut%3E2.0.co;2.
|
| [28] |
Ben Salem K, Ben Abdelaziz A. Principal component analysis (PCA). Tunis Med, 2021, 9943839
|
| [29] |
Infante NA, Faria VS, Cornachione AS, Manchado-Gobatto FB, Zagatto AM, Beck WR. Melatonin decreases PAX7 and CK increment after exercise-induced skeletal muscle damage. Sport Sci Health, 2025, 21: 1521-31.
|
| [30] |
Murray B, Rosenbloom C. Fundamentals of glycogen metabolism for coaches and athletes. Nutr Rev, 2018, 76424359.
|
| [31] |
Wang T, Wang J, Hu X, Huang XJ, Chen GX. Current understanding of glucose transporter 4 expression and functional mechanisms. World J Biol Chem, 2020, 1137698.
|
| [32] |
Xu L, Li D, Li H, Zhang O, Huang Y, Shao H, et al. Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet. Nutr diabetes, 2022, 12142.
|
| [33] |
Pi A, Villivalam SD, Kang S. The molecular mechanisms of fuel utilization during exercise. Biology, 2023, 12111450.
|
| [34] |
Rigamonti AE, Rubino FM, Caroli D, Bondesan A, Mai S, Cella SG, et al. Effects of melatonin on exercise-induced oxidative stress in adults with obesity undergoing a multidisciplinary body weight reduction program. J Clin Med, 2024, 13175216.
|
| [35] |
Fernández-Lázaro D, Arribalzaga S, Gutiérrez-Abejón E, Azarbayjani MA, Mielgo-Ayuso J, Roche E. Omega-3 fatty acid supplementation on post- exercise inflammation, muscle damage, oxidative response, and sports performance in physically healthy adults- a systematic review of randomized controlled trials. Nutrients, 2024, 16132044.
|
| [36] |
Amrollahi-Sharifabadi M, Oladejo TO, Ibrahim AS, Shakoor B, Mehrpour O, Sadeghi-Hashjin G, et al. Melatonin’s paradox: from therapeutic benefits to toxicity warnings. Chem Biol Interact, 2025, 417: 111556.
|
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Universidade Federal De São Carlos
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