Jundishapur Journal of Medical Sciences

Jundishapur Journal of Medical Sciences

The Effect of Regular Aerobic Training and Melatonin Consumption on the Activity of NF-κB and Nrf2 genes and Oxidant Factors in the Heart tissue of Male Wistar Rats Model of Type 1 Diabetes

Document Type : Original Article

Authors
Ali Aminiparsa 1
Marina Shariati 2
Motahareh Joband 1
1 Department of Physical Education & Sport Sciences, Islamic Azad University, Ahvaz Branch. Ahvaz, Iran.
2 Assistant Professor, Department of Physical Education & Sport Sciences, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.
10.32592/JSMJ.23.3.233
Abstract
Background and Objectives NF-κB and Nrf2 are key regulators of oxidative stress. This study investigated the effects of regular aerobic exercise and melatonin on NF-κB and Nrf2 gene expression and oxidative stress markers in the heart tissue of diabetic male rats.
Subjects and Methods Forty male Wistar rats were randomly assigned to five groups: control, diabetic, diabetic + melatonin, diabetic + exercise, and diabetic + melatonin + exercise. Diabetes was induced by streptozotocin. Exercise groups underwent 42 days of treadmill running (15 m/min, 30 min/day). Melatonin (10 mg/kg) was administered intraperitoneally for 42 days. Heart tissue was analyzed for NF-κB and Nrf2 gene expression (real-time PCR) and oxidative stress markers (MDA and TAC, ELISA).
Results Combined aerobic exercise and melatonin significantly decreased NF-κB gene expression while increasing Nrf2 expression compared to the diabetic group. Moreover, MDA levels were reduced, and TAC levels were elevated in the treatment groups.
Conclusion Aerobic exercise and melatonin supplementation synergistically ameliorated diabetic cardiomyopathy by attenuating oxidative stress and inflammation. These findings suggest a potential preventive role for this combined intervention.
Keywords
Diabetes
Aerobic exercise
Melatonin
Oxidative stress
Cardiomyopathy
Subjects

  •  

    • Ghalavand A, Azadi M, Mohammadpour Z, Ghalavand N, Ghalavand M, Ghalavand M. Cognitive Complications of Type 1 Diabetes: A Narrative Review Study. Jundishapur Scientific Medical Journal. 2023 Jan 21;21(6):910-22.
    • Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine. 2019 Jan 1;47(1):22-7. [1016/j.mpmed.2014.09.007] [PMID]
    • Ghalavand A, Motamedi P, Rajabi H, Khaledi N. Effect of diabetes induction and exercisetraining on the level of ascorbic acid and muscle SVCT2 in male Wistar rats. Journal of Shahid Sadoughi University of Medical Sciences. 2020 May 19.
    • Ghalavand A, Saki H, Nazem F, Khademitab N, Behzadi Nezhad H, Behbodi M, Zeighami F. The effect of ganoderma supplementation and selected exercise training on glycemic control in boys with type 1 diabetes. Jundishapur Scientific Medical Journal. 2021 Sep 23;20(4):356-65.
    • Hölscher ME, Bode C, Bugger H. Diabetic cardiomyopathy: does the type of diabetes matter?. International journal of molecular sciences. 2016 Dec 18;17(12):2136. [3390/ijms
      17122136      ] [PMID]
    • De Geest B, Mishra M. Role of oxidative stress in diabetic cardiomyopathy. Antioxidants. 2022 Apr 15;11(4):784. [
      3390/antiox11040784      ] [PMID]
    • Cai LU, Kang YJ. Oxidative stress and diabetic cardiomyopathy: a brief review. Cardiovascular toxicology. 2001 Sep;1:181-93. [1385/ct:1:3:181 ] [PMID]
    • Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 2014 Apr;57:660-71. [1007/
      s00125-014-3171-6      ] [PMID]
    • Jimenez MT, Frenis K, Hahad O, Steven S, Cohen G, Cuadrado A, Muenzel T, Daiber A. Protective actions of nuclear factor erythroid 2-related factor 2 (NRF2) and downstream pathways against environmental stressors. Free Radical Biology and Medicine. 2022 Jul 1;187:72-91. [1016/j.freeradbiomed.
      2022.05.016      ] [PMID]
    • Saha S, Buttari B, Panieri E, Profumo E, Saso L. An overview of Nrf2 signaling pathway and its role in inflammation. Molecules. 2020 Nov 23;25(22):5474. [3390/molecules25225474] [PMID]
    • Sussan TE, Rangasamy T, Blake DJ, Malhotra D, El-Haddad H, Bedja D, Yates MS, Kombairaju P, Yamamoto M, Liby KT, Sporn MB. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proceedings of the National Academy of Sciences. 2009 Jan 6;106(1):250-5. [1073/pnas.08043331
      06      ] [PMID]
    • Wing RR, Goldstein MG, Acton KJ, Birch LL, Jakicic JM, Sallis Jr JF, Smith-West D, Jeffery RW, Surwit RS. Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity. Diabetes care. 2001 Jan 1;24(1):117-23. [2337/diacare.24.1.117] [PMID]
    • Ghalavand A, Ghobadi MR. Effect of Exercise and Insulin Signaling on Glucose Transporter Type 4 in Skeletal Muscles: A narrative review. Journal of Shahid Sadoughi University of Medical Sciences. 2023 Mar 27.
    • Hosseinpour Delavar S, Boyerahmadi A, Soleymani A, Ghalavand A. Effect of eight weeks of aerobic interval training and urtica dioica supplement on some inflammatory indicators and glycemic control in men with type 2 diabetes. Jundishapur Scientific Medical Journal. 2020 Jun 21;19(2):123-35.
    • Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra MC, Hardeland R. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Current topics in medicinal chemistry. 2002 Feb 1;2(2):181-97. [2174/1568026023394443] [PMID]
    • Liu S, Guo Y, Yuan Q, Pan Y, Wang L, Liu Q, Wang F, Wang J, Hao A. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy. Journal of Pineal Research. 2015 Nov;
      59(4):508-17. [1111/jpi.12282] [PMID]
    • Karamitri A, Jockers R. Melatonin in type 2 diabetes mellitus and obesity. Nature Reviews Endocrinology. 2019 Feb;15(2):
      105-25. [1038/s41574-018-0130-1] [PMID]
    • Kumar A, Ilavarasan R, Jayachandran T, Deecaraman M, Aravindan P, Padmanabhan N, Krishan MR. Anti-diabetic activity of Syzygium cumini and its isolated compound against streptozotocin-induced diabetic rats. Journal of Medicinal Plants Research. 2008 Sep 1;2(9):246-9.
    • Shirazi A, Asadi-Amoli F, Sakhaee S, Ghazi-Khansari M, Avand A. Radioprotective effect of melatonin in reducing oxidative stress in rat lenses. Cell Journal (Yakhteh). 2011;13(2):79. [PMID]
    • Chae CH, Jung SL, An SH, Jung CK, Nam SN, Kim HT. Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. Journal of physiology and biochemistry. 2011 Jun;67:235-41. [1007/s
      13105-010-0068-9      ] [PMID]
    • Ghalavand A, Motamedi P, Rajabi H, Khaledi N. Effect of diabetes induction and exercisetraining on the level of ascorbic acid and muscle SVCT2 in male Wistar rats. Journal of Shahid Sadoughi University of Medical Sciences. 2020 May 19.
    • Li L, Luo W, Qian Y, Zhu W, Qian J, Li J, Jin Y, Xu X, Liang G. Luteolin protects against diabetic cardiomyopathy by inhibiting NF-κB-mediated inflammation and activating the Nrf2-mediated antioxidant responses. Phytomedicine. 2019 Jun 1;59:152774. [1016/j.phymed.2018.11.034] [PMID]
    • Thomas CM, Yong QC, Rosa RM, Seqqat R, Gopal S, Casarini DE, Jones WK, Gupta S, Baker KM, Kumar R. Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system. American Journal of Physiology-Heart and Circulatory Physiology. 2014 Oct 1;307(7):H1036-45. [1152/ajpheart.
      00340.2014      ] [PMID]
    • Chen J, Zhang Z, Cai L. Diabetic cardiomyopathy and its prevention by nrf2: current status. Diabetes & metabolism journal. 2014 Oct 17;38(5):337-45. [4093/dmj.2014.38.5.
      337      ] [PMID]
    • Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. Journal of Physiology & Pharmacology. 2019 Dec 1;70(6). [26402/jpp.2019.6.01] [PMID]
    • Magesh S, Chen Y, Hu L. Small molecule modulators of K eap1‐N rf2‐ARE pathway as potential preventive and therapeutic agents. Medicinal research reviews. 2012 Jul;32(4):687-726. [1002/med.21257] [PMID]
    • Georgieva NV, Stoyanchev K, Bozakova N, Jotova I. Combined effects of muscular dystrophy, ecological stress, and selenium on blood antioxidant status in broiler chickens. Biological Trace Element Research. 2011 Sep;142:532-45. [1007/s12011-010-8782-2] [PMID]
    • Zheng J, Cheng J, Zheng S, Zhang L, Guo X, Zhang J, Xiao X. Physical exercise and its protective effects on diabetic cardiomyopathy: what is the evidence?. Frontiers in endocrinology. 2018 Dec 3;9:729. [3389/fendo.2018.00
      729      ] [PMID]
    • Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 signaling by natural products-can it alleviate diabetes?. Biotechnology advances. 2018 Nov 1;36(6):1738-67. [1016/
      j.biotechadv.2017.12.015      ] [PMID]
    • Chen J, Zhang Z, Cai L. Diabetic cardiomyopathy and its prevention by nrf2: current status. Diabetes & metabolism journal. 2014 Oct 17;38(5):337-45. [4093/dmj.2014.38.5.
      337      ] [PMID]
    • Jiang T, Huang Z, Lin Y, Zhang Z, Fang D, Zhang DD. The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes. 2010 Apr 1;59(4):850-60. [2337/
      db09-1342      ] [PMID]
    • Pourhanifeh MH, Hosseinzadeh A, Dehdashtian E, Hemati K, Mehrzadi S. Melatonin: new insights on its therapeutic properties in diabetic complications. Diabetology & metabolic syndrome. 2020 Dec;12:1-20. [1186/s13098-020-00537-z] [PMID]
    • Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomedicine & Pharmacotherapy. 2005 Aug 1;59(7):365-73. [1016/j.biopha.2005.07.002] [PMID]
    • Ahmadi Z, Ashrafizadeh M. Melatonin as a potential modulator of Nrf2. Fundamental & clinical pharmacology. 2020 Feb;34(1):
      11-9. [1111/fcp.12498] [PMID]
    • Zhang W, Wang X, Tang Y, Huang C. Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway. Biomedicine & Pharmacotherapy. 2023 Jun 1;162:
      [10.1016/j.biopha.2023.114591] [PMID]
    • Ke J, Pan J, Lin H, Gu J. Diabetic cardiomyopathy: A brief summary on lipid toxicity. ESC Heart Failure. 2023 Apr;10(2):
      776-90. [1002/ehf2.14224] [PMID]
    • Xiong Z, Li Y, Zhao Z, Zhang Y, Man W, Lin J, Dong Y, Liu L, Wang B, Wang H, Guo B. Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2020 Aug 1;1866(8):165806. [1016/j.bbadis.2020.165806] [PMID]
    • Patel R, Parmar N, Palit SP, Rathwa N, Ramachandran AV, Begum R. Diabetes mellitus and melatonin: Where are we?. Biochimie. 2022 Nov 1;202:2-14. [1016/j.biochi.2022.01.
      001      ] [PMID]
Jundishapur Journal of Medical Sciences
Volume 23, Issue 3 - Serial Number 150
July and August 2024
Pages 233-244

  • Receive Date 04 December 2023
  • Revise Date 01 May 2024
  • Accept Date 08 May 2024