Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats

Abstract

Exercise induces different effects on antioxidant status depending on its intensity. The forced running wheel (FRW) model maintains a constant intensity and volume during exercise. The aim of the present study was to investigate the effects of FRW exercise at different running speeds on several serum biochemical parameters of liver and muscle functions and on oxidative stress biomarkers in skeletal muscle, liver and serum in the rat. Thirty-six male Wistar rats were randomly divided into six groups. Five groups participated in constant power tests at intensities of 10, 13, 14.5, 16, and 17.5 m/min, and a non-exercise group was chosen as the control. Serum, muscle and liver tissues were collected after the tests and analyzed. At speeds >16 m/min, exercise on an FRW significantly increased several serum biochemical parameters, malondialdehyde level and superoxide dismutase activity in all tissues of exercise rats compared with control rats; FRW exercise also increased catalase activity in the liver and glutathione S-transferase activity in muscle, whereas it decreased glutathione level in all tissues and catalase activity in muscle and serum. These data suggest that FRW exercise in rats activates an adaptation of the antioxidant system response in skeletal muscle at speeds <16 m/min, whereas it induces oxidative stress at higher speeds in muscle, liver and serum. In addition, we observed a correlation between the systematic and local oxidative stress status in rats after exercise on FRW.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Gradari, S., Palle, A., McGreevy, K. R., Fontan-Lozano, A. & Trejo, J. L. Can exercise make you smarter, happier, and have more neurons? A hormetic perspective. Front. Neurosci. 10, 93 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Guerreiro, L. F. et al. Oxidative status of the myocardium in response to different intensities of physical training. Physiol. Res. 65, 737–749 (2016).

    Article  CAS  PubMed  Google Scholar 

  3. Emami, S. R., Jafari, M., Haghshenas, R. & Ravasi, A. Impact of eight weeks endurance training on biochemical parameters and obesity-induced oxidative stress in high fat diet-fed rats. J. Exerc. Nutrition Biochem. 20, 29–35 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Vina, J. et al. Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants. IUBMB Life 50, 271–277 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Naderi, R. et al. Voluntary exercise protects heart from oxidative stress in diabetic rats. Adv. Pharm. Bull. 5, 231–236 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Selman, C., McLaren, J. S., Collins, A. R., Duthie, G. G. & Speakman, J. R. Antioxidant enzyme activities, lipid peroxidation, and DNA oxidative damage: the effects of short-term voluntary wheel running. Arch. Biochem. Biophys. 401, 255–261 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Berzosa, C. et al. Acute exercise increases plasma total antioxidant status and antioxidant enzyme activities in untrained men. J. Biomed. Biotechnol. 2011, 540458 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Morillas-Ruiz, J. M. & Hernández-Sánchez, P. Oxidative stress and antioxidant defenses induced by physical exercise. In Basic Principles and Clinical Significance of Oxidative Stress (ed. Gowder, S. J. T.) 221–241 (IntechOpen, 2015). Available from https://www.intechopen.com/books/basic-principles-and-clinical-significance-of-oxidative-stress/oxidative-stress-and-antioxidant-defenses-induced-by-physical-exercise.

  9. Buresh, R. & Berg, K. A tutorial on oxidative stress and redox signaling with application to exercise and sedentariness. Sports Med. Open 1, 3 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Radak, Z. et al. The redox-associated adaptive response of brain to physical exercise. Free Radic. Res. 48, 84–92 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Powers, S. K. & Jackson, M. J. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol. Rev. 88, 1243–1276 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Henriquez-Olguín, C. et al. Adaptations to high-intensity interval training in skeletal muscle require NADPH oxidase 2. Redox Biol. 24, 101188 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Toval, A. et al. Habituation training improves locomotor performance in a forced running wheel system in rats. Front. Behav. Neurosci. 11, 42 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rezaei, S. et al. Evaluation of efforts in untrained Wistar rats following exercise on forced running wheel at maximal lactate steady state. J. Exerc. Nutrition Biochem. 21, 26–32 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Leasure, J. L. & Jones, M. Forced and voluntary exercise differentially affect brain and behavior. Neuroscience 156, 456–465 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Meijer, J. H. & Robbers, Y. Wheel running in the wild. Proc. Biol. Sci. 281, 20140210 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Manchado, F. et al. The maximal lactate steady state is ergometer-dependent in experimental model using rats. Rev. Bras. Med. Esporte 12, 259–262 (2006).

    Article  Google Scholar 

  18. Khazaie, S., Jafari, M., Heydari, J. & Salem, F. Investigating response of spleen and erythrocytes antioxidant defense system on the effects of n-acetyl cysteine against Paraoxon toxicity in rat. Stud. Med. Sci. 26, 176–184 (2015).

    Google Scholar 

  19. Ferreira, J. C. et al. Maximal lactate steady state in running mice: effect of exercise training. Clin. Exp. Pharmacol. Physiol. 34, 760–765 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Contarteze, R. V., Manchado, F., de, B., Gobatto, C. A. & De Mello, M. A. Stress biomarkers in rats submitted to swimming and treadmill running exercises. Comp. Biochem. Physiol. A: Mol. Integr. Physiol. 151, 415–422 (2008).

    Article  CAS  Google Scholar 

  21. Jafari, M. et al. Effects of paraoxon on serum biochemical parameters and oxidative stress induction in various tissues of Wistar and Norway rats. Environ. Toxicol. Pharmacol. 34, 876–887 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Khazaie, S. et al. Modulatory effects of vitamin C on biochemical and oxidative changes induced by acute exposure to diazinon in rat various tissues: prophylactic and therapeutic roles. J. Anim. Physiol. Anim. Nutr. 103, 1619–1628 (2019).

    Article  CAS  Google Scholar 

  23. Clarkson, P. M., Kearns, A. K., Rouzier, P., Rubin, R. & Thompson, P. D. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med. Sci. Sports Exerc. 38, 623–627 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Poprzecki, S., Staszkiewicz, A. & Hubner-Wozniak, E. Effect of eccentric and concentric exercise on plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity in healthy adults. Biol. Sport 21, 193–202 (2004).

    Google Scholar 

  25. Pettersson, J. et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br. J. Clin. Pharmacol. 65, 253–259 (2008).

    Article  PubMed  Google Scholar 

  26. Zhonghui, Z., Xiaowei, Z. & Fang, F. Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice. Saudi J. Biol. Sci. 21, 119–123 (2014).

    Article  CAS  PubMed  Google Scholar 

  27. Forman, H. J., Ursini, F. & Maiorino, M. An overview of mechanisms of redox signaling. J. Mol. Cell. Cardiol. 73, 2–9 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Ayala, A., Muñoz, M. F. & Argüelles, S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev. 2014, 360438 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lin, X., Qu, S., Hu, M. & Jiang, C. Protective effect of erythropoietin on renal injury induced by acute exhaustive exercise in the rat. Int. J. Sports Med. 31, 847–853 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Lima, M. C. et al. Evaluation of oxidative stress in mice subjected to aerobic exercise. Acta Cir. Bras. 27, 544–551 (2012).

    Article  PubMed  Google Scholar 

  31. Acikgoz, O., Aksu, I., Topcu, A. & Kayatekin, B. M. Acute exhaustive exercise does not alter lipid peroxidation levels and antioxidant enzyme activities in rat hippocampus, prefrontal cortex and striatum. Neurosci. Lett. 406, 148–151 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Bejma, J. & Ji, L. L. Aging and acute exercise enhance free radical generation in rat skeletal muscle. J. Appl. Physiol. 87, 465–470 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Vukovic, R. et al. Impact of ovariectomy, high fat diet, and lifestyle modifications on oxidative/antioxidative status in the rat liver. Croat. Med. J. 55, 218–227 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Belviranlı, M. & Gökbel, H. Acute exercise induced oxidative stress and antioxidant changes. Eur. J. Gen. Med. 3, 126–131 (2006).

    Google Scholar 

  35. Jackson, M. J. Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 2285–2291 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Holloway, T. M., Bloemberg, D., da Silva, M. L., Quadrilatero, J. & Spriet, L. L. High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, R927–R934 (2015).

    Article  CAS  PubMed  Google Scholar 

  37. Wang, P., Li, C. G., Qi, Z., Cui, D. & Ding, S. Acute exercise induced mitochondrial H2O2 production in mouse skeletal muscle: association with p66Shc and FOXO3a signaling and antioxidant enzymes. Oxid. Med. Cell. Longev. 2015, 536456 (2015).

    PubMed  PubMed Central  Google Scholar 

  38. Gomes, M. J. et al. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget 8, 20428–20440 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Vargas-Mendoza, N. et al. Antioxidant and adaptative response mediated by Nrf2 during physical exercise. Antioxidants 8, 196 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  40. Sallam, N. & Laher, I. Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases. Oxid. Med. Cell. Longev. 2016, 7239639 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. Kerksick, C. & Willoughby, D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress. J. Int. Soc. Sports Nutr. 2, 38–44 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kayatekin, B. M., Gönenç, S., Açikgöz, O., Uysal, N. & Dayi, A. Effects of sprint exercise on oxidative stress in skeletal muscle and liver. Eur. J. Appl. Physiol. 87, 141–144 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Ji, L. L. Exercice-induced oxidative stress in the heart. In Handbook of Oxidants and Antioxidants in Exercise (eds. Sen, C. K., Packer, L. & Hänninen, O. O. P.) 689–712 (Elsevier Science, Amsterdam, Netherlands, 1994).

  44. Margaritelis, N. V. et al. Blood reflects tissue oxidative stress: a systematic review. Biomarkers 20, 97–108 (2015).

    Article  CAS  PubMed  Google Scholar 

  45. Veskoukis, A. S., Nikolaidis, M. G., Kyparos, A. & Kouretas, D. Blood reflects tissue oxidative stress depending on biomarker and tissue studied. Free Radic. Biol. Med. 47, 1371–1374 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. da Rocha, R. F. et al. Vascular redox imbalance in rats submitted to chronic exercise. Cell Biochem. Funct. 28, 190–196 (2010).

    Article  CAS  PubMed  Google Scholar 

  47. Leeuwenburgh, C. & Ji, L. L. Glutathone and glutathione ethyl ester supplementation of mice alter glutathione homeostasis during exercise. J. Nutr. 128, 2420–2426 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Veskoukis, A. S. et al. Effects of xanthine oxidase inhibition on oxidative stress and swimming performance in rats. Appl. Physiol. Nutr. Metab. 33, 1140–1154 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. You, T. et al. Oxidative stress response in normal and antioxidant supplemented rats to a downhill run: changes in blood and skeletal muscles. Can. J. Appl. Physiol. 30, 677–689 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Ramos, D., Martins, E. G., Viana-Gomes, D., Casimiro-Lopes, G. & Salerno, V. P. Biomarkers of oxidative stress and tissue damage released by muscle and liver after a single bout of swimming exercise. Appl. Physiol. Nutr. Metab. 38, 507–511 (2013).

    Article  CAS  PubMed  Google Scholar 

  51. Tanner, R. K., Fuller, K. L. & Ross, M. L. Evaluation of three portable blood lactate analysers: lactate pro, lactate scout and lactate plus. Eur. J. Appl. Physiol. 109, 551–559 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Winterbourn, C. C., Hawkins, R. E., Brian, M. & Carrell, R. W. The estimation of red cell superoxide dismutase activity. J. Lab. Clin. Med. 85, 337–341 (1975).

    CAS  PubMed  Google Scholar 

  53. Aebi, H. Catalase in vitro. Methods Enzymol. 105, 121–126 (1984).

    Article  CAS  PubMed  Google Scholar 

  54. Habig, W. H. & Jakoby, W. B. Glutathione S-transferases (rat and human). Methods Enzymol. 77, 218–231 (1981).

    Article  CAS  PubMed  Google Scholar 

  55. Tietze, F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal. Biochem. 27, 502–522 (1969).

    Article  CAS  PubMed  Google Scholar 

  56. Satoh, K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin. Chim. Acta 90, 37–43 (1978).

    Article  CAS  PubMed  Google Scholar 

  57. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Javad Rasouli from Baqiyatallah University of Medical Sciences for his assistance. This work was supported by a grant from Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

Authors

Contributions

S.R.M. performed the experiments; M.J. designed the study, contributed to the methodology, wrote, reviewed and edited the manuscript; S.R. performed the experiments and statistical analysis; H. A-a designed the study and provided resources; V. S. contributed to the methodology.

Corresponding author

Correspondence to Mahvash Jafari.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mousavi, S.R., Jafari, M., Rezaei, S. et al. 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 Anim 49, 119–125 (2020). https://doi.org/10.1038/s41684-020-0503-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41684-020-0503-7

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research