Effect of aerobic training and royal jelly on some factors of cardiac apoptosis in obese rats

Document Type : Original Article

Authors

Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

Abstract

Background and Objective: Obesity is associated with dyslipidemia, which leads to elevated triglyceride levels, apoptosis and compromised cardiac function. The aim of this study was to investigate the effect of aerobic training (AT) and royal jelly (RJ) on apoptosis indices in cardiomyocytes in high-fat diet-induced obese rats.
Materials and Methods: In this experimental study, 45 male rats were randomly divided into five groups (n=9): Normal Diet (ND), High-Fat Diet (HFD), High-Fat Diet+Training (HFDT), High-Fat Diet+Royal Jelly (HFDRJ), and High-Fat Diet+Training+Royal Jelly (HFDTRJ). The supplement groups received 100 mg of royal jelly (kg/body weight) diluted in distilled water orally during the intervention period. The aerobic exercise program included treadmill running with an intensity of 50-60% oxygen consumption (VO2max), 5 days/week for 8 weeks. Data were analyzed using ANOVA at p<0.05.
Results: HFD decreased Bcl2 (p=0.006), increased BAX (p=0.006) and BAX/Bcl2 (p=0.006). AT, RJ as well as the combination of AT with RJ increased Bcl2 and decreased BAX and BAX/Bcl2 (p≤0.05). Increase in Bcl2 and decrease in BAX and BAX/Bcl2 were significant in HFDTRJ group compared to HFDT and HFDRJ groups (p≤0.05).
Conclusion: Combining AT with RJ may improve apoptotic markers in cardiomyocytes by affecting BAX and Bcl2 expression and control HFD-induced cardiomyocytes damage on the apoptotic pathway.

Keywords


  1. Ortega FB, Lavie CJ, Blair SN. Obesity and cardiovascular disease. Circulation Research 2016;118(11):1752-70.  doi: 10.1161/CIRCRESAHA.115.306883.
  2. Apovian CM, Gokce N. Obesity and cardiovascular disease. Circulation 2012;125(9):1178-82. doi: 10.1161/CIRCULATIONAHA.111.022541.
  3. WHO I. Obesity and overweight 2018.
  4. He Y, Shi M, Wu J, Sun Z, Guo J, Liu Y, et al. Effects of a high-fat diet on intracellular calcium (Ca2+) handling and cardiac remodeling in Wistar rats without hyperlipidemia. Ultrastructural Pathology 2020;44(1):42-51.  doi: 10.1080/01913123.2019.1709932.
  5. Relling DP, Esberg LB, Fang CX, Johnson WT, Murphy EJ, Carlson EC, et al. High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis. Journal of Hypertension 2006;24(3):549-61. doi: 10.1097/01.hjh.0000203846.34314.94.
  6. Pagidipati NJ, Zheng Y, Green JB, McGuire DK, Mentz RJ, Shah S, et al. Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS. American Heart Journal 2020;219:47-57. doi: 10.1016/j.ahj.2019.09.016.
  7. Pourrazi H, Asgharpour-Arshad M, Gholami F, Abbasi S. Effect of high-intensity interval training on apoptotic gene expression in rat myocardial tissue. Gene Cell and Tissue 2020;7(2):1-6. doi:5812/gct.101963
  8. Lee S-D, Kuo W-W, Wu C-H, Lin Y-M, Lin JA, Lu M-C, et al. Effects of short-and long-term hypobaric hypoxia on Bcl2 family in rat heart. International Journal of Cardiology 2006;108(3):376-84. doi: 10.1016/j.ijcard.2005.05.046.
  9. Cury-Boaventura MF, Levada-Pires AC, Folador A, Gorjão R, Alba-Loureiro TC, Hirabara SM, et al. Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide. European Journal of Applied Physiology 2008;103(3):289. doi: 10.1007/s00421-008-0702-1.
  10. Lee S-D, Shyu W-C, Cheng I-S, Kuo C-H, Chan Y-S, Lin Y-M, et al. Effects of exercise training on cardiac apoptosis in obese rats. Nutrition, Metabolism and Cardiovascular Diseases 2013;23(6):566-73. doi: 10.1016/j.numecd.2011.11.002.
  11. 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. Journal of Applied Physiology 2008;105(6):1934-43. doi: 10.1152/japplphysiol.00037.2008.
  12. Javid Tabrizi N, Bashiri J, Narimani Rad M. Effect of 12 weeks of treadmill aerobic training on cytochrome c and caspase-9 gene expression in cardiac muscle of male rats. Qom University of Medical Sciences Journal 2017;11(6):1-9. URL: http://journal.muq.ac.ir/article-1-869-en.html
  13. Ho T-J, Huang C-C, Huang C-Y, Lin W-T. Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise training-induced cardiac hypertrophy, apoptosis and fibrosis in rats. European Journal of Applied Physiology 2012;112(8):2943-55. doi: 10.1007/s00421-011-2270-z.
  14. Demir E, Aslan A. Protective effect of pristine C60 fullerene nanoparticle in combination with curcumin against hyperglycemia‐induced kidney damage in diabetes caused by streptozotocin. Journal of Food Biochemistry 2020;44(11):e13470. doi: 10.1111/jfbc.13470.
  15. Aslan A, Gok O, Beyaz S, Ağca CA, Erman O, Zerek A. Ellagic acid prevents kidney injury and oxidative damage via regulation of Nrf-2/NF-κB signaling in carbon tetrachloride induced rats. Molecular Biology Reports 2020;47(10):7959-70. doi: 10.1007/s11033-020-05873-x.
  16. Hossen MS, Ali MY, Jahurul M, Abdel-Daim MM, Gan SH, Khalil MI. Beneficial roles of honey polyphenols against some human degenerative diseases: A review. Pharmacological Reports 2017;69(6):1194-205. doi: 10.1016/j.pharep.2017.07.002.
  17. Guo J, Wang Z, Chen Y, Cao J, Tian W, Ma B, et al. Active components and biological functions of royal jelly. Journal of Functional Foods 2021;82:104514. doi:10.1016/j.jff.2021.104514
  18. Aslan A, Can MI, Gok O, Beyaz S, Parlak G, Ozercan IH. The inducing of caspase and Bcl-2 pathway with royal jelly decreases the muscle tissue damage exposed with fluoride in rats. Environmental Science and Pollution Research 2022;29(7):10547-57.  doi: 10.1007/s11356-021-16456-z.
  19. Valiollahpoor Amiri M, Deldar H, Ansari Pirsaraei Z. Impact of supplementary royal jelly on in vitro maturation of sheep oocytes: genes involved in apoptosis and embryonic development. Systems Biology in Reproductive Medicine 2016;62(1):31-8.doi: 10.3109/19396368.2015.1088102.
  20. Jenkhetkan W, Thitiorul S, Jansom C, Ratanavalachai T. Molecular and cytogenetic effects of Thai royal jelly: modulation through c-MYC, h-TERT, NRF2, HO-1, BCL2, BAX and cyclins in human lymphocytes in vitro. Mutagenesis 2017;32(5):525-31. doi: 10.1093/mutage/gex020.
  21. Mostafavian M, Abdi A, Mehrabani J, Barari A. Effect of Eight Weeks of Aerobic Progressive Training with Capsaicin on Changes in PGC-1α and UPC-1 Expression in Visceral Adipose Tissue of Obese Rats With Diet. Complementary Medicine Journal 2020;10(2):106-17. http://cmja.arakmu.ac.ir/article-1-733-en.html
  22. Rocha-Rodrigues S, Rodríguez A, Gouveia AM, Gonçalves IO, Becerril S, Ramírez B, et al. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sciences 2016;165:100-8. doi: 10.1016/j.lfs.2016.09.023.
  23. Mesri Alamdari N, Irandoost P, Roshanravan N, Vafa M, Asghari Jafarabadi M, Alipour S, et al. Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity. Nutrition & Metabolism 2020;17:1-13. doi: 10.1186/s12986-020-00458-8.
  24. Dake BL, Oltman CL. Cardiovascular, metabolic, and coronary dysfunction in high‐Fat‐Fed obesity‐resistant/prone rats. Obesity 2015;23(3):623-9. doi: 10.1002/oby.21009.
  25. Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. The Journal of Clinical Investigation 2017;127(1):1-4. doi: 10.1172/JCI92035.
  26. Lee MK, Yvan-Charvet L, Masters SL, Murphy AJ, editors. The modern interleukin-1 superfamily: Divergent roles in obesity. Seminars in Immunology 2016;28(5):441-449. doi: 10.1016/j.smim.2016.10.001.
  27. Carvalheira JBC, Qiu Y, Chawla A. Blood spotlight on leukocytes and obesity. Blood, The Journal of the American Society of Hematology 2013;122(19):3263-7. doi: 10.1182/blood-2013-04-459446.
  28. Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. The Journal of Clinical Investigation 2017;127(1):43-54. doi: 10.1172/JCI88880.
  29. Wang Y, Qian Y, Fang Q, Zhong P, Li W, Wang L, et al. Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2. Nature Communications 2017;8(1):1-13. doi: 10.1038/ncomms13997.
  30. Ghajari H, Hosseini SA, Farsi S. The Effect of Endurance Training Along with Cadmium Consumption on Bcl-2 and Bax Gene Expressions in Heart Tissue of Rats. Annals of Military and Health Sciences Research 2019;17(1). doi:5812/amh.86795
  31. Sadighi A, Abdi A, Azarbayjani MA, Barari A. Effect of aerobic exercise on some factors of cardiac apoptosis in male rats. Feyz Journal of Kashan University of Medical Sciences 2019;23(5):495-502. URL: http://feyz.kaums.ac.ir/article-1-3792-en.html
  32. Safrazadeh gargari S, Matin homaei H, Azarbayjani Ma. Effects of continues exercise on BAX and BCL-2 heart proteins following by different dos of H2O2 consumption in rat male. The Journal of Shahid Sadoughi University of Medical Sciences 2018;26(4):363-79.doi: 10.22049/JASSP.2019.26218.1175
  33. Sun M, Dawood F, Wen W-H, Chen M, Dixon I, Kirshenbaum LA, et al. Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction. Circulation 2004;110(20):3221-8. doi: 10.1161/01.CIR.0000147233.10318.23.
  34. Machado MV, Vieira AB, da Conceição FG, Nascimento AR, da Nóbrega ACL, Tibirica E. Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome. Experimental Physiology 2017;102(12):1716-28. doi: 10.1113/EP086416. Epub 2017 Oct 26.
  35. Riahi S, Mohammadi MT, Sobhani V, Soleimany M. Chronic effects of aerobic exercise on gene expression of LOX-1 receptor in the heart of rats fed with high fat diet. Iranian Journal of Basic Medical Sciences 2015;18(8):805. PMID: 26557970
  36. Chen X, Li H, Wang K, Liang X, Wang W, Hu X, et al. Aerobic exercise ameliorates myocardial inflammation, fibrosis and apoptosis in high-fat-diet rats by inhibiting P2X7 purinergic receptors. Frontiers in Physiology 2019:1286. doi: 10.3389/fphys.2019.01286.
  37. Oh Y-S, Kwon H-Y, Jeong S-J, Park K-Y, Kim S-Y, Lee H-J, et al. Sojucktang induces apoptosis via loss of mitochondrial membrane potential and caspase-3 activation in KLE human endometrial cancer cells. Chinese Science Bulletin 2009;54(23):4387-92.org/10.1007/s11434-009-0656-7
  38. Razavi Majd Z, Matin Homaee H, Azarbayjani M, Farzanegi P. Effects of Concurrent Regular Aerobic Training and Garlic Extract on Cardiac Tissue Apoptosis Markers in Aged Rats with Chronic Kidney Disease. Journal of Medicinal Plants 2017;2(62):46-54. URL: http://jmp.ir/article-1-1344-en.html
  39. Koçtürk S, Kayatekin B, Resmi H, Açıkgöz O, Kaynak C, Özer E. The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats. European Journal of applied Physiology 2008;102(5):515-24. doi: 10.1007/s00421-007-0612-7.
  40. Kwak H-B. Effects of aging and exercise training on apoptosis in the heart. Journal of Exercise Rehabilitation 2013;9(2):212. doi: 10.1007/s00421-007-0612-7.
  41. Liu W, He W, Li H. Exhaustive training increases uncoupling protein 2 expression and decreases Bcl-2/Bax ratio in rat skeletal muscle. Oxidative Medicine and Cellular Longevity 2013;2013:780719. doi: 10.1155/2013/780719. Epub 2013 Jan 9.
  42. Aslan A, Gok O, Beyaz S, Can MI, Parlak G, Gundogdu R, et al. Royal jelly regulates the caspase, Bax and COX-2, TNF-α protein pathways in the fluoride exposed lung damage in rats. Tissue and Cell 2022;76:101754.  doi: 10.1016/j.tice.2022.101754.
  43. Albalawi AE, Althobaiti NA, Alrdahe SS, Alhasani RH, Alaryani FS, BinMowyna MN. Antitumor Activity of Royal Jelly and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice. BioMed Research International 2022;7233997. doi: 10.1155/2022/7233997.
  44. Martinello M, Mutinelli F. Antioxidant activity in bee products: A review. Antioxidants. 2021;10(1):71. doi: 10.3390/antiox10010071.
  45. Bhosale PB, Ha SE, Vetrivel P, Kim HH, Kim SM, Kim GS. Functions of polyphenols and its anticancer properties in biomedical research: a narrative review. Translational Cancer Research. 2020;9(12):7619. doi: 10.21037/tcr-20-2359.
  46. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.  doi: 10.3390/nu12020457.
  47. Hoseinzade I, Abdi A, Abbassi Daloii A. Protective Effect of Aerobic Training and Royal Jelly on Oxidative Stress in Cardiomyocytes in Obese Rats. Journal of Mazandaran University of Medical Sciences. 2022;31(206):30-42. http://jmums.mazums.ac.ir/article-1-17599-en.html
  48. Sadighi A, Abdi A, Azarbayjani MA, Barari A. Effect of aerobic training and berberine chloride supplementation on oxidative stress indices in the heart tissue of streptozotocin-induced diabetic rats. Journal of Ilam University of Medical Sciences. 2020;28(4):54-65. URL: http://sjimu.medilam.ac.ir/article-1-6170-en.html