Document Type : Original Article
Authors
1 Department Physical Education, Farhangian University, P.O.Box 14665-889, Tehran, Iran
2 Department Exercise Physiology, University of Bu-Ali Sina, Hamedan, Iran
3 Department Exersice Physiology, University of Guilan, Rasht, Iran
Abstract
BACKGROUND: The present study evaluated the effects of aerobic training with variable intensities on apoptotic indices of cardiac tissue in fatty diabetic rats.
METHODS: Twenty-four male Wistar rats were randomly divided into non-diabetic (ND, n=8), trained diabetic (TD, n=8), and control diabetic (CD, n=8) groups. Following a high-fat dietary regimen, type 2 diabetes was induced by streptozotocin, with blood glucose levels above 300 mg/dL considered indicative of diabetes. The TD group underwent aerobic exercise five times a week for six weeks. Subsequently, measurements were taken for left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF%), catalase, caspase-9, P53, glucose, insulin, and HOMA-IR.
RESULTS: Aerobic training led to a significant decrease in blood glucose levels (P < 0.01), caspase-9 (P < 0.05), HOMA-IR (P < 0.05), and P53 expression (P < 0.001) compared with the CD group. LVEDV and LVESV decreased significantly (P < 0.05 for both), while LVEF increased significantly (P < 0.05). Catalase activation showed an insignificant increase in the TD group pre- to post-training compared to CD.
CONCLUSION: Incremental aerobic exercise training (6 weeks) may exert a cardioprotective effect in diabetic rats by reducing apoptosis and oxidative stress indices, while simultaneously increasing aerobic fitness and reducing body weight.
Keywords
1. Kanter M, Aksu F, Takir M, Kostek O, Kanter B, Oymagil A. Effects of Low Intensity Exercise Against Apoptosis and Oxidative Stress in Streptozotocin-induced Diabetic Rat Heart. Exp Clin Endocrinol Diabetes. 2017 Oct;125(9):583-91. https://doi.org/10.1055/s-0035-1569332
2. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972 Nov 8;30(6):595-602. https://doi.org/10.1016/0002-9149(72)90595-4
3. Chen Y, Hua Y, Li X, Arslan IM, Zhang W, Meng G. Distinct Types of Cell Death and the Implication in Diabetic Cardiomyopathy. Front Pharmacol. 2020 Feb 7;11:42. https://doi.org/10.3389%2Ffphar.2020.00042
4. Wang GG, Li W, Lu XH, Zhao X, Xu L. Taurine attenuates oxidative stress and alleviates cardiac failure in type I diabetic rats. Croat Med J. 2013 Apr;54(2):171-9. https://doi.org/10.3325%2Fcmj.2013.54.171
5. Li GX, Jiao XH, Cheng XB. Correlations between blood uric acid and the incidence and progression of type 2 diabetes nephropathy. Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):506-11. https://doi.org/10.26355/eurrev_201801_14202
6. Joubert M, Manrique A, Cariou B, Prieur X. Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways. Diabetes Metab. 2019 Jun;45(3):238-47. https://doi.org/10.1016/j.diabet.2018.07.003
7. Rosa CM, Xavier NP, Henrique Campos D, Fernandes AA, Cezar MD, Martinez PF, et al. Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats. Cardiovasc Diabetol. 2013 Oct 17;12:152. https://doi.org/10.1186%2F1475-2840-12-152
8. Byrne NJ, Rajasekaran NS, Abel ED, Bugger H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radic Biol Med. 2021 Jun;169:317-42. https://doi.org/10.1016/j.freeradbiomed.2021.03.046
9. French JP, Hamilton KL, Quindry JC, Lee Y, Upchurch PA, Powers SK. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J. 2008 Aug;22(8):2862-71. https://doi.org/10.1096%2Ffj.07-102541
10. Wohaieb SA, Godin DV. Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. Diabetes. 1987 Sep;36(9):1014-8. https://doi.org/10.2337/diab.36.9.1014
11. Rasouli Mojez M, Ali Gaeini A, Choobineh S, Sheykhlouvand M. Hippocampal Oxidative Stress Induced by Radiofrequency Electromagnetic Radiation and the Neuroprotective Effects of Aerobic Exercise in Rats: A Randomized Control Trial. J Phys Act Health. 2021 Oct 25;18(12):1532-38. https://doi.org/10.1123/jpah.2021-0213
12. Huang ML, Chiang S, Kalinowski DS, Bae DH, Sahni S, Richardson DR. The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis. Oxid Med Cell Longev. 2019 Apr 7;2019:6392763. https://doi.org/10.1155/2019/6392763
13. Phaneuf S, Leeuwenburgh C. Apoptosis and exercise. Med Sci Sports Exerc. 2001 Mar;33(3):393-6. https://doi.org/10.1097/00005768-200103000-00010
14. Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care. 2005 Apr;28(4):799-805. https://doi.org/10.2337/diacare.28.4.799
15. Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015 Apr 22;35(3):e00199. https://doi.org/10.1042%2FBSR20140141
16. Kuo WW, Chung LC, Liu CT, Wu SP, Kuo CH, Tsai FJ, et al. Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin-induced diabetic rats. Cell Biochem Funct. 2009 Oct;27(7):479-87. https://doi.org/10.1002/cbf.1601
17. Sayevand Z, Nazem F, Nazari A, Sheykhlouvand M, Forbes SC. Cardioprotective effects of exercise and curcumin supplementation against myocardial ischemia–reperfusion injury. Sport Sci Health. 2022; 18(3): 1011-19. https://doi.org/10.1007/s11332-021-00886-w
18. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006 Jul 14;126(1):107-20. https://doi.org/10.1016/j.cell.2006.05.036
19. Kim B, Hart P, Kang M, Roth S, Brown MD, Hagberg JM, et al. Functional Study of Tumor Suppressor p53 Gene Variation: Effect on Cardiovascular Adaptation to Exercise Training. Exp Biol. 2012; 26(S1):1138-45. https://doi.org/10.1096/fasebj.26.1_supplement.1138.5
20. Gu J, Wang S, Guo H, Tan Y, Liang Y, Feng A, et al. Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis. Cell Death Dis. 2018 Jan 23;9(2):82. https://doi.org/10.1038/s41419-017-0093-5
21. Gharaat MA, Kashef M, Jameie B, Rajabi H. Regulation of PI3K and Hand2 gene on physiological hypertrophy of heart following high-intensity interval, and endurance training. J Res Med Sci. 2019 Apr 26;24:32. https://doi.org/10.4103%2Fjrms.JRMS_292_18
22. Sheykhlouvand M, Gharaat M, Khalili E, Agha-Alinejad H, Rahmaninia F, Arazi H. Low-Volume High-Intensity Interval Versus Continuous Endurance Training: Effects on Hematological and Cardiorespiratory System Adaptations in Professional Canoe Polo Athletes. J Strength Cond Res. 2018 Jul;32(7):1852-60. https://doi.org/10.1519/jsc.0000000000002112
23. Lavie CJ, Johannsen N, Swift D, Sénéchal M, Earnest C, Church T, et al. Exercise is Medicine - The Importance of Physical Activity, Exercise Training, Cardiorespiratory Fitness and Obesity in the Prevention and Treatment of Type 2 Diabetes. Eur Endocrinol. 2014 Feb;10(1):18-22. https://doi.org/10.17925%2FEE.2014.10.01.18
24. Exercise training for type 2 diabetes mellitus: impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009 Jun 30;119(25):3244-62. https://doi.org/10.1161/circulationaha.109.192521
25. Veeranki S, Givvimani S, Kundu S, Metreveli N, Pushpakumar S, Tyagi SC. Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice. J Mol Cell Cardiol. 2016 Mar;92:163-73. https://doi.org/10.1016/j.yjmcc.2016.01.023
26. Derouich M, Boutayeb A. The effect of physical exercise on the dynamics of glucose and insulin. J Biomech. 2002 Jul;35(7):911-7. https://doi.org/10.1016/s0021-9290(02)00055-6
27. Sheykhlouvand M, Khalili E, Gharaat M, Arazi H, Khalafi M, Tarverdizadeh B. Practical Model of Low-Volume Paddling-Based Sprint Interval Training Improves Aerobic and Anaerobic Performances in Professional Female Canoe Polo Athletes. J Strength Cond Res. 2018 Aug;32(8):2375-82. https://doi.org/10.1519/jsc.0000000000002152
28. Fereshtian S, Sheykhlouvand M, Forbes S, Agha-Alinejad H, Gharaat M. Physiological and performance responses to high-intensity interval training in female inline speed skaters. Apunts. Med. l’Esport 2017; 52:131-8. https://doi.org/10.1016/j.apunts.2017.06.003
29. Sheykhlouvand M, Gharaat M. Optimal homeostatic stress to maximize the homogeneity of adaptations to interval interventions in soccer players. Front Physiol. 2024; 15, 1377552. https://doi.org/10.3389/fphys.2024.1377552
30. Sheykhlouvand M, Gharaat M, Khalili E, Agha-Alinejad H. The effect of high-intensity interval training on ventilatory threshold and aerobic power in well-trained canoe polo athletes. Sci Sports. 2016;31, 283-89. https://doi.org/10.1016/j.scispo.2016.02.007
31. Sheykhlouvand M, Arazi H, Astorino TA, Suzuki K. Effects of a New Form of Resistance-Type High-Intensity Interval Training on Cardiac Structure, Hemodynamics, and Physiological and Performance Adaptations in Well-Trained Kayak Sprint Athletes. Front Physiol. 2022 Mar 10;13:850768. https://doi.org/10.3389/fphys.2022.850768
32. Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007 Dec;14(6):753-60. https://doi.org/10.1097/hjr.0b013e3281eacef1
33. Gharaat MA, Sheykhlouvand M, Eidi LA. Performance and recovery: effects of caffeine on a 2000-m rowing ergometer. Sport Sci Health. 2020; 16:531-42. https://doi.org/10.1007/s11332-020-00643-5
34. Barzegar H, Arazi H, Mohebbi H, Sheykhlouvand M, Forbes SC. Caffeine coingested with carbohydrate on performance recovery in national-level paddlers: a randomized, double-blind, crossover, placebo-controlled trial. J Sports Med Phys Fitness. 2022 Mar;62(3):337-342. https://doi.org/10.23736/s0022-4707.21.12125-5
35. Song W, Kwak HB, Lawler JM. Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):517-28. https://doi.org/10.1089/ars.2006.8.517
36. Gharaat MA, Kashef M, Jameie SB, Rajabi H. Effect of endurance and high intensity interval swimming training on cardiac hypertrophy of male rats. J Shahid Sadoughi Uni Med Sci. 2018; 26(4): 306-18.
37. Jakicic JM, Jaramillo SA, Balasubramanyam A, Banc-roft B, Curtis JM, Mathews A, et al. Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study. Int J Obes (Lond). 2009 Mar;33(3):305-16. https://doi.org/10.1038/ijo.2008.280
38. Sheykhlouvand M, Forbes SC. Aerobic capacities, anaerobic power, and anthropometric characteristics of elite female canoe polo players based on playing position. Sport Sci Health. 2017; 14:19–24. https://doi.org/10.1007/s11332-017-0395-0
39. Sheykhlouvand M, Gharaat M, Bishop P, Khalili E, Karami E, Fereshtian S. Anthropometric, physiological, and performance characteristics of elite canoe polo players. Psychol Neurosci. 2015; 8(2), 257–66. https://psycnet.apa.org/doi/10.1037/pne0000013
40. Samadi M, Nazem F, Gharaat MA. Designing the simulation training of taekwondo competition according to heart rate, blood lactate and rating of perceived exertion. Med dello Sport. 2014;67(4):581-92.
41. Peterson JM, Bryner RW, Sindler A, Frisbee JC, Alway SE. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol (1985). 2008 Dec;105(6):1934-43. https://doi.org/10.1152/japplphysiol.00037.2008
42. Pieri BL, Souza DR, Luciano TF, Marques SO, Pauli JR, Silva AS, et al. Effects of physical exercise on the P38MAPK/REDD1/14-3-3 pathways in the myocardium of diet-induced obesity rats. Horm Metab Res. 2014 Aug;46(9):621-7. https://doi.org/10.1055/s-0034-1371824
43. Cai L, Kang YJ. Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol. 2003;3(3):219-28. https://doi.org/10.1385/ct:3:3:219
44. Ho TJ, Huang CC, Huang CY, Lin WT. Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise training-induced cardiac hypertrophy, apoptosis and fibrosis in rats. Eur J Appl Physiol. 2012 Aug;112(8):2943-55. https://doi.org/10.1007/s00421-011-2270-z
45. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 2004 Apr 1;64(7):2627-33. https://doi.org/10.1158/0008-5472.can-03-0846
46. Rodrigues B, Jorge L, Mostarda CT, Rosa KT, Medeiros A, Malfitano C, et al. Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction. J Card Fail. 2012 Sep;18(9):734-44. https://doi.org/10.1016/j.cardfail.2012.07.006
2. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972 Nov 8;30(6):595-602. https://doi.org/10.1016/0002-9149(72)90595-4
3. Chen Y, Hua Y, Li X, Arslan IM, Zhang W, Meng G. Distinct Types of Cell Death and the Implication in Diabetic Cardiomyopathy. Front Pharmacol. 2020 Feb 7;11:42. https://doi.org/10.3389%2Ffphar.2020.00042
4. Wang GG, Li W, Lu XH, Zhao X, Xu L. Taurine attenuates oxidative stress and alleviates cardiac failure in type I diabetic rats. Croat Med J. 2013 Apr;54(2):171-9. https://doi.org/10.3325%2Fcmj.2013.54.171
5. Li GX, Jiao XH, Cheng XB. Correlations between blood uric acid and the incidence and progression of type 2 diabetes nephropathy. Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):506-11. https://doi.org/10.26355/eurrev_201801_14202
6. Joubert M, Manrique A, Cariou B, Prieur X. Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways. Diabetes Metab. 2019 Jun;45(3):238-47. https://doi.org/10.1016/j.diabet.2018.07.003
7. Rosa CM, Xavier NP, Henrique Campos D, Fernandes AA, Cezar MD, Martinez PF, et al. Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats. Cardiovasc Diabetol. 2013 Oct 17;12:152. https://doi.org/10.1186%2F1475-2840-12-152
8. Byrne NJ, Rajasekaran NS, Abel ED, Bugger H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radic Biol Med. 2021 Jun;169:317-42. https://doi.org/10.1016/j.freeradbiomed.2021.03.046
9. French JP, Hamilton KL, Quindry JC, Lee Y, Upchurch PA, Powers SK. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J. 2008 Aug;22(8):2862-71. https://doi.org/10.1096%2Ffj.07-102541
10. Wohaieb SA, Godin DV. Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. Diabetes. 1987 Sep;36(9):1014-8. https://doi.org/10.2337/diab.36.9.1014
11. Rasouli Mojez M, Ali Gaeini A, Choobineh S, Sheykhlouvand M. Hippocampal Oxidative Stress Induced by Radiofrequency Electromagnetic Radiation and the Neuroprotective Effects of Aerobic Exercise in Rats: A Randomized Control Trial. J Phys Act Health. 2021 Oct 25;18(12):1532-38. https://doi.org/10.1123/jpah.2021-0213
12. Huang ML, Chiang S, Kalinowski DS, Bae DH, Sahni S, Richardson DR. The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis. Oxid Med Cell Longev. 2019 Apr 7;2019:6392763. https://doi.org/10.1155/2019/6392763
13. Phaneuf S, Leeuwenburgh C. Apoptosis and exercise. Med Sci Sports Exerc. 2001 Mar;33(3):393-6. https://doi.org/10.1097/00005768-200103000-00010
14. Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care. 2005 Apr;28(4):799-805. https://doi.org/10.2337/diacare.28.4.799
15. Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015 Apr 22;35(3):e00199. https://doi.org/10.1042%2FBSR20140141
16. Kuo WW, Chung LC, Liu CT, Wu SP, Kuo CH, Tsai FJ, et al. Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin-induced diabetic rats. Cell Biochem Funct. 2009 Oct;27(7):479-87. https://doi.org/10.1002/cbf.1601
17. Sayevand Z, Nazem F, Nazari A, Sheykhlouvand M, Forbes SC. Cardioprotective effects of exercise and curcumin supplementation against myocardial ischemia–reperfusion injury. Sport Sci Health. 2022; 18(3): 1011-19. https://doi.org/10.1007/s11332-021-00886-w
18. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006 Jul 14;126(1):107-20. https://doi.org/10.1016/j.cell.2006.05.036
19. Kim B, Hart P, Kang M, Roth S, Brown MD, Hagberg JM, et al. Functional Study of Tumor Suppressor p53 Gene Variation: Effect on Cardiovascular Adaptation to Exercise Training. Exp Biol. 2012; 26(S1):1138-45. https://doi.org/10.1096/fasebj.26.1_supplement.1138.5
20. Gu J, Wang S, Guo H, Tan Y, Liang Y, Feng A, et al. Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis. Cell Death Dis. 2018 Jan 23;9(2):82. https://doi.org/10.1038/s41419-017-0093-5
21. Gharaat MA, Kashef M, Jameie B, Rajabi H. Regulation of PI3K and Hand2 gene on physiological hypertrophy of heart following high-intensity interval, and endurance training. J Res Med Sci. 2019 Apr 26;24:32. https://doi.org/10.4103%2Fjrms.JRMS_292_18
22. Sheykhlouvand M, Gharaat M, Khalili E, Agha-Alinejad H, Rahmaninia F, Arazi H. Low-Volume High-Intensity Interval Versus Continuous Endurance Training: Effects on Hematological and Cardiorespiratory System Adaptations in Professional Canoe Polo Athletes. J Strength Cond Res. 2018 Jul;32(7):1852-60. https://doi.org/10.1519/jsc.0000000000002112
23. Lavie CJ, Johannsen N, Swift D, Sénéchal M, Earnest C, Church T, et al. Exercise is Medicine - The Importance of Physical Activity, Exercise Training, Cardiorespiratory Fitness and Obesity in the Prevention and Treatment of Type 2 Diabetes. Eur Endocrinol. 2014 Feb;10(1):18-22. https://doi.org/10.17925%2FEE.2014.10.01.18
24. Exercise training for type 2 diabetes mellitus: impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009 Jun 30;119(25):3244-62. https://doi.org/10.1161/circulationaha.109.192521
25. Veeranki S, Givvimani S, Kundu S, Metreveli N, Pushpakumar S, Tyagi SC. Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice. J Mol Cell Cardiol. 2016 Mar;92:163-73. https://doi.org/10.1016/j.yjmcc.2016.01.023
26. Derouich M, Boutayeb A. The effect of physical exercise on the dynamics of glucose and insulin. J Biomech. 2002 Jul;35(7):911-7. https://doi.org/10.1016/s0021-9290(02)00055-6
27. Sheykhlouvand M, Khalili E, Gharaat M, Arazi H, Khalafi M, Tarverdizadeh B. Practical Model of Low-Volume Paddling-Based Sprint Interval Training Improves Aerobic and Anaerobic Performances in Professional Female Canoe Polo Athletes. J Strength Cond Res. 2018 Aug;32(8):2375-82. https://doi.org/10.1519/jsc.0000000000002152
28. Fereshtian S, Sheykhlouvand M, Forbes S, Agha-Alinejad H, Gharaat M. Physiological and performance responses to high-intensity interval training in female inline speed skaters. Apunts. Med. l’Esport 2017; 52:131-8. https://doi.org/10.1016/j.apunts.2017.06.003
29. Sheykhlouvand M, Gharaat M. Optimal homeostatic stress to maximize the homogeneity of adaptations to interval interventions in soccer players. Front Physiol. 2024; 15, 1377552. https://doi.org/10.3389/fphys.2024.1377552
30. Sheykhlouvand M, Gharaat M, Khalili E, Agha-Alinejad H. The effect of high-intensity interval training on ventilatory threshold and aerobic power in well-trained canoe polo athletes. Sci Sports. 2016;31, 283-89. https://doi.org/10.1016/j.scispo.2016.02.007
31. Sheykhlouvand M, Arazi H, Astorino TA, Suzuki K. Effects of a New Form of Resistance-Type High-Intensity Interval Training on Cardiac Structure, Hemodynamics, and Physiological and Performance Adaptations in Well-Trained Kayak Sprint Athletes. Front Physiol. 2022 Mar 10;13:850768. https://doi.org/10.3389/fphys.2022.850768
32. Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007 Dec;14(6):753-60. https://doi.org/10.1097/hjr.0b013e3281eacef1
33. Gharaat MA, Sheykhlouvand M, Eidi LA. Performance and recovery: effects of caffeine on a 2000-m rowing ergometer. Sport Sci Health. 2020; 16:531-42. https://doi.org/10.1007/s11332-020-00643-5
34. Barzegar H, Arazi H, Mohebbi H, Sheykhlouvand M, Forbes SC. Caffeine coingested with carbohydrate on performance recovery in national-level paddlers: a randomized, double-blind, crossover, placebo-controlled trial. J Sports Med Phys Fitness. 2022 Mar;62(3):337-342. https://doi.org/10.23736/s0022-4707.21.12125-5
35. Song W, Kwak HB, Lawler JM. Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):517-28. https://doi.org/10.1089/ars.2006.8.517
36. Gharaat MA, Kashef M, Jameie SB, Rajabi H. Effect of endurance and high intensity interval swimming training on cardiac hypertrophy of male rats. J Shahid Sadoughi Uni Med Sci. 2018; 26(4): 306-18.
37. Jakicic JM, Jaramillo SA, Balasubramanyam A, Banc-roft B, Curtis JM, Mathews A, et al. Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study. Int J Obes (Lond). 2009 Mar;33(3):305-16. https://doi.org/10.1038/ijo.2008.280
38. Sheykhlouvand M, Forbes SC. Aerobic capacities, anaerobic power, and anthropometric characteristics of elite female canoe polo players based on playing position. Sport Sci Health. 2017; 14:19–24. https://doi.org/10.1007/s11332-017-0395-0
39. Sheykhlouvand M, Gharaat M, Bishop P, Khalili E, Karami E, Fereshtian S. Anthropometric, physiological, and performance characteristics of elite canoe polo players. Psychol Neurosci. 2015; 8(2), 257–66. https://psycnet.apa.org/doi/10.1037/pne0000013
40. Samadi M, Nazem F, Gharaat MA. Designing the simulation training of taekwondo competition according to heart rate, blood lactate and rating of perceived exertion. Med dello Sport. 2014;67(4):581-92.
41. Peterson JM, Bryner RW, Sindler A, Frisbee JC, Alway SE. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol (1985). 2008 Dec;105(6):1934-43. https://doi.org/10.1152/japplphysiol.00037.2008
42. Pieri BL, Souza DR, Luciano TF, Marques SO, Pauli JR, Silva AS, et al. Effects of physical exercise on the P38MAPK/REDD1/14-3-3 pathways in the myocardium of diet-induced obesity rats. Horm Metab Res. 2014 Aug;46(9):621-7. https://doi.org/10.1055/s-0034-1371824
43. Cai L, Kang YJ. Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol. 2003;3(3):219-28. https://doi.org/10.1385/ct:3:3:219
44. Ho TJ, Huang CC, Huang CY, Lin WT. Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise training-induced cardiac hypertrophy, apoptosis and fibrosis in rats. Eur J Appl Physiol. 2012 Aug;112(8):2943-55. https://doi.org/10.1007/s00421-011-2270-z
45. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 2004 Apr 1;64(7):2627-33. https://doi.org/10.1158/0008-5472.can-03-0846
46. Rodrigues B, Jorge L, Mostarda CT, Rosa KT, Medeiros A, Malfitano C, et al. Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction. J Card Fail. 2012 Sep;18(9):734-44. https://doi.org/10.1016/j.cardfail.2012.07.006
)