Effects of different-intensity exercise and creatine supplementation on mitochondrial biogenesis and redox status in mice

Document Type : Original Article

Authors

1 Department of Physiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey

2 Department of Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

3 Department of Histology and Embryology, Faculty of Medicine, Harran University, Sanliurfa, Turkey

4 Department of Nutrition and Dietetics, Faculty of Health Sciences, Harran University, Sanliurfa, Turkey

Abstract

Objective(s): Dietary supplementation combined with exercise may potentiate the beneficial effects of exercise by reducing exercise-induced oxidative stress and improving mitochondrial quality and capacity. In this study, the effects of creatine monohydrate (CrM) supplementation with low and high-intensity exercise on mitochondrial biogenesis regulators, Nrf2 anti-oxidant signaling pathway and muscle damage levels were investigated. 
Materials and Methods: Balb/c male mice were divided into six experimental groups: control, control+CrM, high-intensity exercise, high-intensity exercise+CrM, low-intensity exercise, and low-intensity exercise+CrM. Mice were given CrM supplementation and at the same time, low and high-intensity exercise was applied to the groups on the treadmill at 30min/5day/8week. Then, mitochondrial biogenesis marker (PGC-1α, NRF-1, TFAM), Nrf2 and HO-1 protein expressions, total oxidant-anti-oxidant status level, and histopathological changes were investigated in serum and muscle tissue. 
Results: Exercise intensity and CrM supplementation were found to be effective factors in mitochondrial biogenesis induction via the PGC-1α signaling pathway. Nrf2 and HO-1 protein levels increased with exercise intensity, and this result was directly related to serum oxidative stress markers. In addition, CrM supplementation was effective in reducing exercise-induced muscle damage. 
Conclusion: This combination induced skeletal muscle adaptations, including mitochondrial biogenesis and enhanced anti-oxidant reserves. This synergistic effect of dietary supplementation with low-intensity exercise may be valuable as a complement to treatment, especially in diseases caused by mitochondrial dysfunction.

Keywords

References

1. Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 2020; 11:1–11. 
2. Zhu J, Wang KZQ, Chu CT. After the banquet: mitochondrial biogenesis, mitophagy, and cell survival. Autophagy 2013; 9:1663–1676. 
3. Chandel NS. Evolution of mitochondria as signaling organelles. Cell Metab 2015; 22:204–206. 
4. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem 2010; 47:69–84. 
5. Austin S, St-Pierre J. PGC1α and mitochondrial metabolism–emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 2012; 125:4963–4971. 
6. Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab 2012; 23:459–466. 
7. Brunetta HS, Holwerda AM, Van Loon LJC, Holloway GP. Mitochondrial ROS and aging: understanding exercise as a preventive tool. J Sci Sport Exerc 2020; 2:15–24. 
8. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2008; 417:1–13. 
9. Nosrati N, Bakovic M, Paliyath G. Molecular mechanisms and pathways as targets for cancer prevention and progression with dietary compounds. Int J Mol Sci 2017; 18:2050-2072. 
10. Magesh S, Chen Y, Hu L. Small molecule modulators of keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Med Res Rev 2012; 32:687–726. 
11. Suzuki T, Motohashi H, Yamamoto M. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci 2013; 34:340–346. 
12. Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, et al. Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med 2012; 52:366–376. 
13. Stecker RA, Harty PS, Jagim AR, Candow DG, Kerksick CM. Timing of ergogenic aids and micronutrients on muscle and exercise performance. J Int Soc Sports Nutr 2019; 16:1–8. 
14. Andres S, Ziegenhagen R, Trefflich I, Pevny S, Schultrich K, Braun H, et al. Creatine and creatine forms intended for sports nutrition. Mol Nutr Food Res 2017; 61:1–18. 
15. Claudino JG, Mezêncio B, Amaral S, Zanetti V, Benatti F, Roschel H, et al. Creatine monohydrate supplementation on lower-limb muscle power in Brazilian elite soccer players. J Int Soc Sports Nutr 2014; 11:32-38. 
16. Poortmans JR, Rawson ES, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 11. Br J Sports Med 2010; 44:765–766. 
17. Chaoqun L, Yuqi Z, Shi Z, Zhenghui Y, Li W. A comparison of the antioxidant effects between hydrogen gas inhalation and vitamin C supplementation in response to a 60-min treadmill exercise in rat gastrocnemius muscle. Front Physiol 2021; 12:745194-745206. 
18. Thirupathi A, Wang M, Lin JK, Fekete G, István B, Baker JS, et al. Effect of different exercise modalities on oxidative stress: a systematic review. BioMed Res Int 2021; 1947928:1-10. 
19. Jackson MJ. Free radicals generated by contracting muscle: by-products of metabolism or key regulators of muscle function? Free Radic Biol Med 2008; 44:132–141. 
20. Mani S, Swargiary G, Singh M, Agarwal S, Dey A, Ojha S, et al. Mitochondrial defects: an emerging theranostic avenue towards alzheimer’s associated dysregulations. Life Sci 2021; 285:119985-. 
21. Chen X, Li L, Guo J, Zhang L, Yuan Y, Chen B, et al. Treadmill running exercise prevents senile osteoporosis and upregulates the wnt signaling pathway in SAMP6 mice. Oncotarget 2016; 7:71072–71086. 
22. Kayacan Y, Çetinkaya A, Yazar H, Makaracı Y. Oxidative stress response to different exercise intensity with an automated assay: thiol/disulphide homeostasis. Arch Physiol Biochem 2021; 127:504–508.
23. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38:1103–1111. 
24. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37:277–285. 
25. Vasconcelos AB, Nampo FK, Molina JC, Silva MB, Oliveira AS, de Angelis TR, et al. Modulation of exercise-induced muscular damage and hyperalgesia by different 630 nm doses of light-emitting diode therapy (LEDT) in rats. Lasers Med Sci 2019; 34:749–758. 
26. Cai M, Wang Q, Liu Z, Jia D, Feng R, Tian Z. Effects of different types of exercise on skeletal muscle atrophy, antioxidant capacity and growth factors expression following myocardial infarction. Life Sci 2018; 213:40–49. 
27. McGee SL, Hargreaves M. Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit. Nat Rev Endocrinol 2020; 16:495–505. 
28. Hargreaves M, Spriet LL. Skeletal muscle energy metabolism during exercise. Nat Metab 2020; 2:817–828. 
29. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 2008; 88:1243–1276. 
30. Oh S, Komine S, Warabi E, Akiyama K, Ishii A, Ishige K, et al. Nuclear factor (erythroid derived 2)-like 2 activation increases exercise endurance capacity via redox modulation in skeletal muscles. Sci Rep 2017; 7:1–11. 
31. Jiaming Y, Rahimi MH. Creatine supplementation effect on recovery following exercise-induced muscle damage: a systematic review and meta-analysis of randomized controlled trials. J Food Biochem 2021; 45:1–13. 
32. Arazi H, Eghbali E, Suzuki K. Creatine supplementation, physical exercise and oxidative stress markers: a review of the mechanisms and effectiveness. Nutrients 2021; 13:1–17. 
33. Deminice R, Afonso A. Creatine supplementation reduces oxidative stress biomarkers after acute exercise in rats. Amino Acids 2012; 43:709–715. 
34. Deminice R, Rosa FT, Franco GS, Jordao AA, de Freitas EC. Effects of creatine supplementation on oxidative stress and inflammatory markers after repeated-sprint exercise in humans. Nutrition 2013; 29: 1127–1132. 
35. Taskin S, Celik H, Demiryurek S, Taskin A. The bidirectional effect of creatine supports the maintenance of oxidant-antioxidant homeostasis during exercise. Int J Res 2021; 9:18–28. 
36. González-Bartholin R, Mackay K, Valladares D, Zbinden-Foncea H, Nosaka K, Peñailillo L. Changes in oxidative stress, inflammation and muscle damage markers following eccentric versus concentric cycling in older adults. Eur J Appl Physiol 2019; 119:2301–2312. 
37. Bonilla DA, Kreider RB, Stout JR, Forero DA, Kerksick CM, Roberts MD, et al. Metabolic basis of creatine in health and disease: a bioinformatics-assisted review. Nutrients 2021; 13:1–32. 
38. Peake JM, Markworth JF, Nosaka K, Raastad T, Wadley GD, Coffey VG. Modulating exercise-induced hormesis: Does less equal more? J Appl Physiol 2015; 119:72–89. 
39. Wang P, Li CG, Qi Z, Cui D, Ding S. Acute exercise stress promotes Ref1/Nrf2 signalling and increases mitochondrial antioxidant activity in skeletal muscle. Exp Physiol 2016; 101:410–420. 
40. Tutakhail A, Nazary QA, Lebsir D, Kerdine-Romer S, Coudore F. Induction of brain Nrf2-HO-1 pathway and antinociception after different physical training paradigms in mice. Life Sci 2018; 209:149–156. 
41. Mei T, Liu Y, Wang J, Zhang Y. MiR-340-5p: a potential direct regulator of Nrf2 expression in the post-exercise skeletal muscle of mice. Mol Med Rep 2019; 19:1340–1348. 
42. Vilela TC, Effting PS, dos Santos Pedroso G, Farias H, Paganini L, Rebelo Sorato H, et al. Aerobic and strength training induce changes in oxidative stress parameters and elicit modifications of various cellular components in skeletal muscle of aged rats. Exp Gerontol 2018; 106:21–27. 
43. Gomes MJ, Martinez PF, Pagan LU, Damatto RL, Cezar MDM, Lima ARR, et al. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget 2017; 8:20428–20440. 
44. Pinho RA, Aguiar AS, Radák Z. Effects of resistance exercise on cerebral redox regulation and cognition: an interplay between muscle and brain. Antioxidants 2019; 8:529-544.
45. Mesquita PHC, Vann CG, Phillips SM, McKendry J, Young KC, Kavazis AN, et al. Skeletal muscle ribosome and mitochondrial biogenesis in response to different exercise training modalities. Front Physiol 2021; 12: 725866-725878. 
46. Memme JM, Erlich AT, Phukan G, Hood DA. Exercise and mitochondrial health. J Physiol 2021; 599:803–817. 
47. Porter C, Reidy PT, Bhattarai N, Sidossis LS, Rasmussen BB. Resistance exercise training alters mitochondrial function in human skeletal muscle. Med Sci Sport Exerc 2015; 47:1922-1931. 
48. Thirupathi A, de Souza CT. Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise. J Physiol Biochem 2017; 73:487–494. 
49. Powers SK, Ji LL, Kavazis AN, Jackson MJ. Reactive oxygen species: impact on skeletal muscle. Compr Physiol 2011; 1:941–969. 
50. Heiat F, Ghanbarzadeh M, Shojaeifard M, Ranjbar R. The effect of high-intensity interval training on the expression levels of PGC-1α and SIRT3 proteins and aging index of slow-twitch and fast-twitch of healthy male rats. Sci Sport 2020; 1–6. 
51. Leick L, Plomgaard P, Grønlykke L, Al-Abaiji F, Wojtaszewski JFP, Pilegaard H. Endurance exercise induces mRNA expression of oxidative enzymes in human skeletal muscle late in recovery. Scand J Med Sci Sports 2010; 20:593–599. 
52. Terada S, Tabata I. Effects of acute bouts of running and swimming exercise on PGC-1α protein expression in rat epitrochlearis and soleus muscle. Am J Physiol Metab 2004; 286:208–216. 
53. Holloway GP. Nutrition and training influences on the regulation of mitochondrial adenosine diphosphate sensitivity and bioenergetics. Sport Med 2017; 47:13–21. 
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 8
August 2022
Pages 1009-1015

Files

Share

How to cite

Statistics