Document Type : Original Article
1. Introduction and Objective
Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide. Its incidence has increased dramatically in recent decades, positioning it as a major risk factor for cardiovascular disease. T2DM is characterized by chronic hyperglycemia which, through mechanisms such as exacerbated oxidative stress, chronic inflammation, and mitochondrial dysfunction, can lead to structural and functional damage in vital organs, particularly the heart. Indeed, many diabetes-related cardiovascular complications result from an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidant defense systems—a state defined as oxidative stress. Oxidative stress is a primary driver of diabetic cardiomyopathy, especially in the aging population. Regular physical activity is recognized as a non-pharmacological strategy to bolster antioxidant defenses and mitigate oxidative damage. This study aimed to compare the effects of eight weeks of aerobic and concurrent training on the activity of antioxidant enzymes and lipid peroxidation in the cardiac tissue of elderly, overweight, diabetic male rats.
2. Materials and Methods
This experimental study was conducted on 30 elderly male Wistar rats (aged 24–28 months; mean weight approximately 320 g). Animals were housed under standardized laboratory conditions: temperature 20–22°C, humidity 55–65%, and a 12:12-hour light-dark cycle. They had ad libitum access to water and standard pellet feed, sourced from Khallaghan-e Teb Pouya (Tehran, Iran). The feed was verified for chemical and microbial quality and formulated with high-quality proteins, essential fatty acids, vitamins, and minerals, without synthetic preservatives. After diabetes induction, the rats were randomly assigned to three groups: Control, Aerobic Training (AT), and Concurrent Training (CT). The AT protocol consisted of running at an intensity of 60–75% of Vmax, five sessions per week for eight weeks. The CT protocol combined aerobic running with resistance training (ladder climbing at 60–80% of one-repetition maximum). Forty-eight hours after the final training session, cardiac tissue samples were collected. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA) were measured using ELISA kits. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (P ≤ 0.05).
3. Findings
Significant differences in SOD, CAT, GPX, and MDA levels were observed among the groups (P<0.001). Both training modalities increased antioxidant enzyme activity and decreased MDA levels compared to the control group (P<0.001). Furthermore, concurrent training induced greater improvements than aerobic training alone (P < 0.001).
4. Conclusions
Comparing the two training modalities, improvements in all measured indices were significantly more pronounced in the concurrent training group than in the aerobic training group. This finding suggests that integrating resistance training into an aerobic exercise program provides significant added value in promoting anti-inflammatory and antioxidant adaptations in cardiac tissue. The observed changes, supported by physiological principles, may be attributed to several cellular and molecular mechanisms: Activation of the Nrf2/ARE pathway: Exercise enhances the phosphorylation and nuclear translocation of the Nrf2 transcription factor, upregulating antioxidant genes such as SOD2, CAT, and GPX in cardiomyocytes. Enhanced mitochondrial biogenesis: Activation of the AMPK/PGC-1α signaling pathway promotes mitochondrial biogenesis in cardiomyocytes, thereby reducing electron leakage from the respiratory chain and subsequent reactive oxygen species (ROS) production. Reduction of oxidative stress and lipid peroxidation: The coordinated upregulation of SOD, CAT, and GPX leads to more effective neutralization of ROS, preventing lipid peroxidation of cell membranes, as evidenced by reduced MDA levels. In conclusion, eight weeks of exercise training, particularly concurrent training, enhances the antioxidant capacity and attenuates oxidative stress in the cardiac tissue of elderly diabetic rats. Concurrent training appears to be an effective strategy for mitigating oxidative damage and improving cardiac health in the context of diabetes and aging.
5. Acknowledgment & Funding
This article is not sponsored
6. Ethical Considerations
This research was approved by the ethics committee
with the ethical code of IR.IA.AEC.1404.087.
7. Authors' Contributions
All authors have actively participated in the process of the study and writing the article.
8. Conflict of Interest
The authors declare no conflict of interest.
1. Su X, Chen X, Jiang T, et al. Effects of aerobic exercise plus resistance training on inflammatory factors in elderly women with type 2 diabetes mellitus. Ann Noninvasive Electrocardiol. 2022;27(6):e12996.
2. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. N Engl J Med. 2001;345(5):367‑374.
3. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 5th ed. Oxford: Oxford University Press; 2015.
4. Marx N, Federici M, Schütt K, Müller‑Wieland D, Ajjan RA, Antunes MJ, et al. Diabetes mellitus and cardiovascular diseases. Eur Heart J. 2003;24(6):561‑576.
5. Powers SK, Jackson MJ. Exercise‑induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243‑1276.
6. Gomez‑Cabrera MC, Domenech E, Viña J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med. 2008;44(2):126‑131.
10. Jia, G., Hill, M. A., & Sowers, J. R. Diabetic cardiomyopathy: An update of mechanisms contributing to this clinical entity. Journal of the American College of Cardiology, 2018;71(3), 339–351. https://doi.org/10.1016/j.jacc.2017.11.025.
11. Packer, M., & Kitzman, D. W. Obesity-related heart failure with a preserved ejection fraction: the mechanistic rationale for combining inhibitors of aldosterone, neprilysin, and sodium-glucose cotransporter-2. JACC: Heart Failure,2018; 6(8), 633-639.
12. Marwick, T. H., Hordern, M. D., Miller, T., Chyun, D. A., Bertoni, A. G., Blumenthal, R. S., ... & Rocchini, A. Exercise training for type 2 diabetes mellitus: impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation, 2009;119(25), 3244-3262.
13. Aliabadi, M., Saghebjoo, M., Yakhchali, B., & Shariati, V. Interaction between high-intensity interval training and high-protein diet on gut microbiota composition and body weight in obese male rats. Applied Physiology, Nutrition, and Metabolism,2023; 48(11), 808-828.
14. Qinna, N. A., & Badwan, A. A. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats. Drug design, development and therapy,2015; 2515-2525.
15. Kaydash, O. A., Ivanov, V. V., Vengerovsky, A. I., Buyko, E. E., & Schepetkin, I. A. The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats. Bulletin of Siberian Medicine, 2020;19(2), 41-47.
16. Høydal, M. A., Wisløff, U., Kemi, O. J., & Ellingsen, Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Preventive Cardiology, 2007;14(6), 753-760.
17. Wisloff, U., Helgerud, J., Kemi, O. J., & Ellingsen, O. Intensity-controlled treadmill running in rats: VO2max and cardiac hypertrophy. American Journal of Physiology-Heart and Circulatory Physiology,2001; 280(3), H1301-H1310.
18. He, X., Zheng, S., & Chan, A. W. (2020). Diabetes, oxidative stress and inflammation: A mechanistic link to cardiovascular complications. Oxidative Medicine and Cellular Longevity, 2020; 1–14. https://doi.org/10.1155/2020/.
19. Lourenço Í, Krause Neto W, dos Santos Portella Amorim L, Moraes Munhoz Ortiz V, Lopes Geraldo V, Henrique da Silva Ferreira G, Chagas Caperuto É, Florencio Gama E. Muscle hypertrophy and ladder‐based resistance training for rodents: A systematic review and meta‐analysis. Physiological reports. 2020 Sep;8(17):e14502.
20. Piralaee A, Badrkhan Rashvan O. Aerobic exercise: an approach to regulate oxidative stress in the heart tissue of diabetic rats. Appl Stud Health Sport Physiol. 2024;11(2):128-140. [In Persian]
21. Lino Rodrigues, K., Vieira Dias Da Silva, V., Nunes Goulart da Silva Pereira, E., Rangel Silvares, R., Peres de Araujo, B., Eduardo Ilaquita Flores, E., ... & Daliry, A. Aerobic exercise training improves microvascular function and oxidative stress parameters in diet-induced type 2 diabetic mice. Diabetes, metabolic syndrome and obesity: targets and therapy, 2022;2991-3005.
22. Sadeghi, R., keshavarz, S., Kargarfard, M., banaii, J. The Effects of Aerobic, Resistance, and Combined Exercise on Adiponectin and CTRP-9 Levels in Patients with Type 2 Diabetes Mellitus. Journal of Applied Health Studies in Sport Physiology, 2022; 9(2): 173-187. doi: 10.22049/ jahssp. 2021.27336.1374. [In Persian]
23. Su, X., He, J., Cui, J., Li, H., & Men, J. The effects of aerobic exercise combined with resistance training on inflammatory factors and heart rate variability in middle‐aged and elderly women with type 2 diabetes mellitus. Annals of Noninvasive Electrocardiology, 2022;27(6), e12996.
25. Powers SK, Radak Z, Ji LL. Exercise-induced oxidative stress: Past, present and future. J Physiol. 2020;598(22):5081‑5095.
26. Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M. Exercise‑induced adaptation and oxidative stress. Physiol Rev. 2017;97(2):487‑528.
27. Merry TL, Ristow M. Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? J Physiol. 2016;594(18):5135‑5147.
28. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615‑1625.
29. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The role of therapy. Diabetes Care. 2004;27(3):791‑802.
30. Hawley JA. Molecular responses to endurance and resistance exercise. J Sci Med Sport. 2009;12(1):15‑2.
31. Pashaei, Z., Jafari, A., Alivand, M. The Effect of High Intensity Interval Training on Lipid Profile and Glucose Homeostasis in Overweight / Obese Middle-Aged Women. Journal of Applied Health Studies in Sport Physiology, 2020; 6(2): 56-64. doi: 10.22049/jassp.2020.14018. [In Persian]
32. Rosety-Rodríguez, M., Camacho, A., Rosety, M. Á., Fornieles, G., Diaz, A. J., Rosety, I., ... & Ordonez, F. J. A short-term training program reduced oxidative damage in elderly diabetic rats. Revista de Investigación Clínica, 2013; 65(4), 331-335.
33. Powers, S. K., Radak, Z., & Ji, L. L. Exercise-induced oxidative stress: Past, present and future. The Journal of Physiology, 2020;598(22), 5081–5095.
