Daneshvar Medicine

Daneshvar Medicine

The effect of aerobic exercise with melatonin on GDNF gene expression and some indicators of oxidative stress in male rats with diabetic neuropathic pain

Document Type : Original Article

Authors
Ahmad Kaki 1
Marzieh Karimi 2
1 Department of Sports Physiology, Faculty of Humanities, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran
2 Department of physical education, ahvaz branch, islamic azad university, ahvaz, iran
10.22070/daneshmed.2021.13915.1040
Abstract
Background and Objective: GDNF protects nerve cells against inflammation and oxidative stress caused by hyperglycemia. The aim of this study was to evaluate the effect of aerobic exercise with melatonin on GDNF gene expression and some indicators of oxidative stress in rats with diabetic neuropathic pain.
Materials and Methods: Forty 8-week-old male Wistar rats (weight range 204 ± 11.3 g) were randomly divided into five groups (n = 8) including: diabetic neuropathy (50 mg/ kg streptozotocin intraperitoneal injection), diabetic melatonin neuropathy (mg/kg 10 melatonin daily for 6 weeks), diabetic neuropathy exercise (30 minutes of aerobic exercise at 15 meters per minute, 5 days a week for 6 weeks), diabetes melatonin neuropathy and healthy exercise and control. After confirmation of diabetic neuropathy by behavioral tests, exercise protocol and supplementation were performed. GDNF gene expression was measured by real-time technique and oxidative stress indices in spinal cord tissue by spectrophotometer. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.
Results: Exercise and melatonin reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia. Aerobic exercise with melatonin significantly increased GDNF gene expression and SOD and CAT enzyme activity and decreased MDA concentration compared to diabetic neuropathy group (P <0.05).
Conclusion: Aerobic exercise with melatonin modulates the expression of GDNF gene and oxidative stress indices and improves the sensitivity of nociceptors to pain factors. It is recommended to use aerobic exercise with melatonin for diabetics to reduce neuropathic pain.
Keywords
Aerobic exercise
Melatonin
GDNF
Oxidative stress
Diabetic neuropathic pain

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    1. Feldman EL, Nave K-A, Jensen TS, Bennett DL. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron 2017;93(6):1296-313.
    2. Sloan G, Shillo P, Selvarajah D, Wu J, Wilkinson ID, Tracey I, et al. A new look at painful diabetic neuropathy. Diabetes Research and Clinical Practice 2018;144:177-91.
    3. Schreiber AK, Nones CF, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: physiopathology and treatment. World Journal of Diabetes 2015;6(3):432.
    4. Khan N, Smith MT. Neurotrophins and neuropathic pain: role in pathobiology. Molecules 2015;20(6):10657-88.
    5. Brewster WJ, Fernyhough P, Diemel LT, Mohiuddin L, Tomlinson DR. Diabetic neuropathy, nerve growth factor and other neurotrophic factors. Trends in Neurosciences 1994;17(8):321-5.
    6. Mitroshina ЕV, Mishchenko TA, Shirokova OM, Astrakhanova TA, Loginova MM, Epifanova EA, et al. Intracellular neuroprotective mechanisms in neuron-glial networks mediated by glial cell line-derived neurotrophic factor. Oxidative Medicine and Cellular Longevity 2019(2-3):1-15.
    7. Akkina S, Patterson C, Wright D. GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice. Experimental Neurology. 2001;167(1):173-82.
    8. Leinninger GM, Vincent AM, Feldman EL. The role of growth factors in diabetic peripheral neuropathy. Journal of the Peripheral Nervous System 2004;9(1):26-53.
    9. Metwally MM, Ebraheim LL, Galal AA. Potential therapeutic role of melatonin on STZ-induced diabetic central neuropathy: A biochemical, histopathological, immunohistochemical and ultrastructural study. Acta Histochemica 2018;120(8):828-36.
    10. Safakhah HA, Kor NM, Bazargani A, Bandegi AR, Pourbadie HG, Khoshkholgh-Sima B, et al. Forced exercise attenuates neuropathic pain in chronic constriction injury of male rat: an investigation of oxidative stress and inflammation. Journal of Pain Research 2017;10:1457.
    11. Dobson JL, McMillan J, Li L. Benefits of exercise intervention in reducing neuropathic pain. Frontiers in cellular Neuroscience 2014;8:102.
    12. Yan J-e, Yuan W, Lou X, Zhu T. Streptozotocin-induced diabetic hyperalgesia in rats is associated with upregulation of Toll-like receptor 4 expression. Neuroscience Letters 2012;526(1):54-8.
    13. Morrow TJ. Animal models of painful diabetic neuropathy: the STZ rat model. Current Protocols in Neuroscience 2004. DOI:10.1002/0471142301.ns0918s29
    14. Wei M, Ong L, Smith MT, Ross FB, Schmid K, Hoey AJ, et al. The streptozotocin‐diabetic rat as a model of the chronic complications of human diabetes. Heart Lung & Circulation 2003;12(1):44-50.
    15. Zangiabadi N, Sheibani V, Asadi-Shekaari M, Shabani M, Jafari M, Asadi AR, et al. Effects of melatonin in prevention of neuropathy in STZ-induced diabetic rats. American Journal of Pharmacology and Toxicology 2011;6(2):59-67.
    16. Malmberg AB, Bannon AW. Models of nociception: hot‐plate, tail‐flick, and formalin tests in rodents. Current Protocols in Neuroscience 2007;8-9(8).
    17. Chen Y-W, Hsieh P-L, Chen Y-C, Hung C-H, Cheng J-T. Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats. Anesthesia & Analgesia 2013;116(2):482-90.
    18. Yoon H, Thakur V, Isham D, Fayad M, Chattopadhyay M. Moderate exercise training attenuates inflammatory mediators in DRG of Type 1 diabetic rats. Experimental Neurology 2015;267:107-14.
    19. Rossi DM, Valenti VE, Navega MT. Exercise training attenuates acute hyperalgesia in streptozotocin-induced diabetic female rats. Clinics 2011;66(9):1615-9.
    20. Gong Y-H, Yu X-R, Liu H-L, Yang N, Zuo P-P, Huang Y-G. Antinociceptive effects of combination of tramadol and acetaminophen on painful diabetic neuropathy in streptozotocin-induced diabetic rats. Acta Anaesthesiologica Taiwanica 2011;49(1):16-20.
    21. Chae C-H, Jung S-L, An S-H, Jung C-K, Nam S-N, Kim H-T. 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;67(2):235-41.
    22. Gelderd JB, Chopin SF. The vertebral level of origin of spinal nerves in the rat. The Anatomical Record 1977;188(1):45-7.
    23. Sun Q, Tang D-D, Yin E-G, Wei L-L, Chen P, Deng S-P, et al. Diagnostic significance of serum levels of nerve growth factor and brain derived neurotrophic factor in diabetic peripheral neuropathy. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 2018;24:5943.
    24. Xu P, Rosen KM, Hedstrom K, Rey O, Guha S, Hart C, et al. Nerve injury induces glial cell line‐derived neurotrophic factor (gdnf) expression in schwann cells through purinergic signaling and the pkc‐pkd pathway. Glia 2013;61(7):1029-40.
    25. Sidorova YA, Bespalov MM, Wong AW, Kambur O, Jokinen V, Lilius TO, et al. A novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat. Frontiers in Pharmacology 2017;8:365.
    26. Farmer K. The effect of volunatary exercise on neuropathic pain: University of Kansas; 2010.
    27. Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, Tewari A, et al. Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy. Investigative Ophthalmology & Visual Science 2017;58(12):5594-603.
    28. Wang Z, Li S, Wang Y, Zhang X, Chen L, Sun D. GDNF enhances the anti-inflammatory effect of human adipose-derived mesenchymal stem cell-based therapy in renal interstitial fibrosis. Stem Cell Research 2019;41:101605.
    29. Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxidative Medicine and Cellular Longevity 2013;2013:168039. doi: 10.1155/2013/168039.
    30. Leung L, Cahill CM. TNF-α and neuropathic pain-a review. Journal of Neuroinflammation 2010;7(1):1-11.
    31. Groover AL, Ryals JM, Guilford BL, Wilson NM, Christianson JA, Wright DE. Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice. Pain 2013;154(12):2658-67.
    32. Almeida C, DeMaman A, Kusuda R, Cadetti F, Ravanelli MI, Queiroz AL, et al. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain. Pain 2015;156(3):504-13.
    33. Cooper MA, Kluding PM, Wright DE. Emerging relationships between exercise, sensory nerves, and neuropathic pain. Frontiers in Neuroscience 2016;10:372.
    34. Geng T, Li P, Okutsu M, Yin X, Kwek J, Zhang M, et al. PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. American Journal of Physiology Cell Physiology 2010;298(3):C572-C9.
    35. Chen S-J, Huang S-H, Chen J-W, Wang K-C, Yang Y-R, Liu P-F, et al. Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis. International Immunopharmacology 2016;31:169-77.
    36. Elbe H, Esrefoglu M, Vardi N, Taslidere E, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. Human & Experimental Toxicology 2015;34(9):859-68.
    37. Ogłodek EA, Just MJ, Szromek AR, Araszkiewicz A. Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity. Pharmacological Reports 2016;68(5):945-51.
    38. Muhammad T, Ali T, Ikram M, Khan A, Alam SI, Kim MO. Melatonin rescue oxidative stress-mediated neuroinflammation/neurodegeneration and memory impairment in scopolamine-induced amnesia mice model. Journal of Neuroimmune Pharmacology 2019;14(2):278-94.
    39. Babaei BF, Zare S, Heydari R, Farokhi F. Effects of melatonin and vitamin E on peripheral neuropathic pain in streptozotocin-induced diabetic rats 2010 (13)2:1-8.

     

Daneshvar Medicine
Volume 29, Issue 3 - Serial Number 154
September and October 2021
Pages 132-146