The effect of 8 weeks of vitamin D supplementation and aerobic exercise on sirtuin-1 protein levels and oxidative stress markers of myocardial tissue in middle-aged male rats

Document Type : original article


1 Department of Sport Sciences, Kish International Campus,, University of Tehran, Kish iran

2 Department of sport Sciences, Kish International Campus, University of Tehran Kish, Iran

3 Department of sport physiology, Faculty of Sport Sciences, University of Tehran, Tehran, Iran


Background and Purpose: Exercise training and vitamin D supplementation play an important role in cardiovascular health. However, the effects of combining these two strategies and their molecular role in cardiac adaptations are less known. Therefore, the present study was conducted with the aim of determining the effect of vitamin D supplementation and aerobic exercise on oxidative stress markers and Sirtuin-1 (SIRT-1) levels in the myocardial tissue of middle-aged male rats.
Materials and Methods: Forty male rats (12-14 months, 350-400 g) after two weeks of familiarization and maximal aerobic speed test, were randomly divided into four groups: control (Con), aerobic training (AT), vitamin D (Vit-D) and aerobic exercise + vitamin D (AT+Vit_D) were divided. The training consisted of eight weeks of incremental training (5 days per week). Vit_D and AT+Vit-D groups received 500 units of vitamin D along with 0.3 ml of olive oil (kg/body weight). Olive oil was also used as a placebo. 48 hours after the last intervention session, the heart tissue of the animals was removed. The activities of Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) as well as the concentration of Malondialdehyde (MDA), Hydrogen peroxide (H2O2) and SIRT-1 protein were measured. Data analysis was done by one-way ANOVA test at P < 0.05 level.
Results: The findings showed that the SIRT-1 was significantly higher in the AT than in the Con group (P < 0.05). Also, the MDA levels in the AT were lower than in the Con group (P < 0.05). No significant difference was observed in MDA and SIRT-1 among other groups (P > 0.05). In addition, there was no significant difference in the ‌ GPx, SOD and H2O2 between the groups (P > 0.05).
Conclusion: In general, the findings of the present study showed that regular aerobic exercise is beneficial for reducing oxidative damage to the heart tissue in middle age. Also, aerobic training in middle age leads to an increase in SIRT-1 protein. Considering the important role of SIRT-1 in preventing heart diseases and strengthening the antioxidant defense system, aerobic exercise seems to be an effective strategy to reduce cardiovascular diseases associated with aging. In addition, the findings of the present study showed that vitamin D supplementation along with aerobic exercise does not produce synergistic effects in improving oxidative stress markers or SIRT-1. However, due to the small amount of studies in this regard and also some limitations of the current research, it is suggested to conduct more studies in this regard.


Main Subjects

  1. Smith DL, Fernhall B. Advanced cardiovascular exercise physiology: Human Kinetics; 2011.
  2. Zarrazquin I, Torres-Unda J, Ruiz F, Irazusta J, Kortajarena M, Cillero IH, et al. Longitudinal study: lifestyle and cardiovascular health in health science students. Nutricion hospitalaria. 2014;30(5):1144-51.
  3. Mozaffarian D, Kamineni A, Carnethon M, Djoussé L, Mukamal KJ, Siscovick D. Lifestyle Risk Factors and New-Onset Diabetes Mellitus in Older Adults: The Cardiovascular Health Study. Archives of Internal Medicine. 2009;169(8):798-807.
  4. Vanga SR, Good M, Howard PA, Vacek JL. Role of vitamin D in cardiovascular health. The American journal of cardiology. 2010;106(6):798-805.
  5. Eddy P, Wertheim EH, Kingsley M, Wright BJ. Associations between the effort-reward imbalance model of workplace stress and indices of cardiovascular health: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews. 2017;83:252-66.
  6. An Z, Jin Y, Li J, Li W, Wu W. Impact of particulate air pollution on cardiovascular health. Current Allergy and Asthma Reports. 2018;18(3):1-7.
  7. Driver JA, Djoussé L, Logroscino G, Gaziano JM, Kurth T. Incidence of cardiovascular disease and cancer in advanced age: prospective cohort study. BMJ. 2008;337:a2467.
  8. Santos CX, Anilkumar N, Zhang M, Brewer AC, Shah AM. Redox signaling in cardiac myocytes. Free Radical Biology and Medicine. 2011;50(7):777-93.
  9. Taverne YJ, Bogers AJ, Duncker DJ, Merkus D. Reactive oxygen species and the cardiovascular system. Oxidative medicine and cellular longevity. 2013;2013.
  10. D'Onofrio N, Servillo L, Balestrieri ML. SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection. Antioxidants & redox signaling. 2018;28(8):711-32.
  11. Matsushima S, Sadoshima J. The role of sirtuins in cardiac disease. American Journal of Physiology-Heart and Circulatory Physiology. 2015;309(9):H1375-H89.
  12. Folden DV, Gupta A, Sharma AC, Li SY, Saari JT, Ren J. Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen‐activated protein kinase‐dependent mechanism. British journal of pharmacology. 2003;139(7):1310-6.
  13. Valks DM, Kemp TJ, Clerk A. Regulation of Bcl-xL expression by H2O2 in cardiac myocytes. Journal of Biological Chemistry. 2003;278(28):25542-7.
  14. Leon H, Bautista-Lopez N, Sawicka J, Schulz R. Hydrogen peroxide causes cardiac dysfunction independent from its effects on matrix metalloproteinase-2 activation. Canadian journal of physiology and pharmacology. 2007;85(3-4):341-8.
  15. Kwon SH, Pimentel DR, Remondino A, Sawyer DB, Colucci WS. H2O2 regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways. Journal of molecular and cellular cardiology. 2003;35(6):615-21.
  16. Sefal Manesh S, Khaledi N, Rajabi H, Askari H. The Comparison of the effect of High Intensity Interval and Progressive Resistance Training on Activated Transcription Factor 3 myocardial gene expression in male Diabetic Rats. Journal of Sport and Exercise Physiology. 2021;14(2):67-76.(In Persian).
  17. Ahmadi M, Abbassi Daloii A, Shadmehri S, Agghaei Bahmanbeglu N. Compare the effect of eight weeks aerobic and resistance training on Oxidant, antioxidant status and lipid profile in obese girls. Journal of Sport and Exercise Physiology. 2019;11(1):139-52. (In Persian).
  18. Wimalawansa SJ. Vitamin D deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Biology. 2019;8(2):30.
  19. Pirooz M, Azarbayjani M, Hosseini S, Peeri M. The simultaneous effect of regular exercise and vitamin D on apoptosis level and antioxidant enzymes of heart tissue of male rats exposed to oxygenated water. J Knowledge Health. 2018;13(2):29-42.
  20. Shams Z, Azarbayjani MA, peeri M, Matin Homaee H. The effect of aerobic training and Vitamin Don GPx concentration and PABin lung tissue of rats exposed to Hydrogen Peroxide. Razi Journal of Medical Sciences. 2020;26(12):156-66.
  21. Mehdipoor M, Damirchi A, Tousi SMTR, Babaei P. Concurrent vitamin D supplementation and exercise training improve cardiac fibrosis via TGF-β/Smad signaling in myocardial infarction model of rats. Journal of physiology and biochemistry. 2021;77(1):75-84.
  22. Polidoro L, Properzi G, Marampon F, Gravina GL, Festuccia C, Di Cesare E, et al. Vitamin D protects human endothelial cells from H 2 O 2 oxidant injury through the Mek/Erk-Sirt1 axis activation. Journal of cardiovascular translational research. 2013;6(2):221-31.
  23. Safarpour P, Daneshi-Maskooni M, Vafa M, Nourbakhsh M, Janani L, Maddah M, et al. Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC family practice. 2020;21(1):1-10.
  24. Wisløff U, Helgerud J, Kemi OJ, Ellingsen Ø. Intensity-controlled treadmill running in rats: V̇ o 2 max and cardiac hypertrophy. American journal of physiology-heart and circulatory physiology. 2001;280(3):H1301-H10.
  25. Lu K, Wang L, Wang C, Yang Y, Hu D, Ding R. Effects of high-intensity interval versus continuous moderate‑intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model. Molecular medicine reports. 2015;12(2):2374-82.
  26. Kiran TR, Subramanyam M, Devi SA. Swim exercise training and adaptations in the antioxidant defense system of myocardium of old rats: relationship to swim intensity and duration. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 2004;137(2):187-96.
  27. Tang Z, Wang Y, Zhu X, Ni X, Lu J. Exercise increases cystathionine-γ-lyase expression and decreases the status of oxidative stress in myocardium of ovariectomized rats. International Heart Journal. 2016;57(1):96-103.
  28. Chicco AJ, McCarty H, Reed AH, Story RR, Westerlind KC, Turner RT, et al. Resistance exercise training attenuates alcohol-induced cardiac oxidative stress. European journal of cardiovascular prevention and rehabilitation. 2006;13(1):74-9.
  29. Zhang Z, Wang Y, Xu P, Cui Y, Li W, Cao X. Research of the heart protective effect of exercise precondition mediated by calcitonin gene related peptide on acute exhaustion rats. Zhonghua wei zhong bing ji jiu yi xue. 2018;30(4):369-73.
  30. Wang S-Q, Li D, Yuan Y. Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway. The Journal of Physiological Sciences. 2019;69(6):861-73.
  31. Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, Madrigal-Santillán EO, Morales-Martínez M, Madrigal-Bujaidar E, et al. Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition. Life. 2021;11(11):1269.
  32. Musci RV, Hamilton KL, Linden MA. Exercise-induced mitohormesis for the maintenance of skeletal muscle and healthspan extension. Sports. 2019;7(7):170.
  33. Wang D, Cao H, Wang X, Wang J, Wang M, Zhang J, et al. SIRT1 is required for exercise-induced beneficial effects on myocardial ischemia/reperfusion injury. Journal of Inflammation Research. 2021;14:1283.
  34. Cross WL, Roby MA, Deschenes MR, Harris MB. Myocardial SIRT1 expression following endurance and resistance exercise training in young and old rats. Wiley Online Library; 2008.
  35. Li X, Han X, Zhang H, Tan H, Han S. SIRT1 signaling pathway mediated the protective effects on myocardium of rats after endurance training and acute exhaustive exercise. Zhonghua xin xue guan bing za zhi. 2017;45(6):501-6.
  36. Donniacuo M, Urbanek K, Nebbioso A, Sodano L, Gallo L, Altucci L, et al. Cardioprotective effect of a moderate and prolonged exercise training involves sirtuin pathway. Life sciences. 2019;222:140-7.
  37. Farhangi MA, Nameni G, Hajiluian G, Mesgari-Abbasi M. Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat-diet induced obese rats. BMC cardiovascular disorders. 2017;17(1):1-7.
  38. El-Gohary OA, Allam MM. Effect of vitamin D on isoprenaline-induced myocardial infarction in rats: possible role of peroxisome proliferator-activated receptor-γ. Canadian journal of physiology and pharmacology. 2017;95(6):641-6.
  39. Anandabaskar N, Selvarajan S, Dkhar SA, Kamalanathan SK, Tamilarasu K, Bobby Z. Effect of vitamin D supplementation on vascular functions and oxidative stress in type 2 diabetic patients with vitamin D deficiency. Indian Journal of Endocrinology and Metabolism. 2017;21(4):555.
  40. Yang J, Zhang Y, Pan Y, Sun C, Liu Z, Liu N, et al. The protective effect of 1, 25 (OH) 2D3 on myocardial function is mediated via sirtuin 3-regulated fatty acid metabolism. Frontiers in Cell and Developmental Biology. 2021;9:627135.
  • Receive Date: 14 August 2022
  • Revise Date: 14 September 2022
  • Accept Date: 03 October 2022
  • First Publish Date: 21 February 2023
  • Publish Date: 21 March 2023