Sport Physiology

Sport Physiology

Effect of six-week endurance exercise and hydroalcoholic extract of Urtica dioica on blood glucose level and necrotic cells of the hippocampal CA3 region of Wistar rats in type 1 diabetes model

Document Type : Research Paper

Authors
maryam keshvari 1
Masoud Rahmati 2
Rahim Mirnasuri 3
Farzaneh Chehelcheraghi 4
1 Ph.D. candidate of exercise physiology, Lorestan University
2 Associate Professor of Exercise Physiology, Lorestan University
3 Assistant Professor of Exercise Physiology, Lorestan University
4 Assistant Professor of Anatomical Sciences, Lorestan University Medical of Sciences
10.22089/spj.2020.8033.1969
Abstract
Due to the antioxidant effect of exercise and Urtica dioica(UD),the aim of this study was to evaluate the effects of these interventions on changes in blood glucose and necrotic cells in the CA3 region of the type 1 diabetic rat hippocampus.In this study,76 Wistar rats were divided into healthy(control,exercise,UD,UD-exercise) and diabetes (control, exercise,UD,UD-exercise)groups. Diabetes was induced by intraperitoneal injection of streptozotocin(45mg/kg) and 48 hours after injection, blood glucose levels above 300mg/dl were the criteria for confirmation of diabetes.After confirmation of diabetes, endurance exercise protocol with moderate-intensity(5days/week)and daily gavage of hydro alcoholic extract of Urtica dioica was performed at 50mg/kg for six weeks. 48 hours after the last session, the rats were sacrificed and the hippocampal tissue was extracted and fixed in 10% formalin for staining of crystal violet for necrotic cell count. Data were analyzed using ANOVA and Kruskal-Wallis tests using Bonferroni post hoc test at significance levelα=0.05. Results showed that six weeks of endurance exercise and consumption of UD extract significantly reduced blood glucose concentration in the diabetic-exercise(p=0.001),diabetes-UD(p=0.001)and diabetes-exercise-UD(p=0.001)groups compared with the diabetes-control group. In addition, there was a significant difference between the diabetes-UD and diabetes-exercise-UD(p=0.001)and diabetes-exercise and diabetes-exercise-UD(p=0.002) groups.The interaction between endurance exercise and consumption of UD extract significantly decreased the number of necrotic cells in the diabetes-exercise-UD group compared to the diabetic-control group (p=0.029).Finally, 6 weeks of endurance exercise and consumption of hydro alcoholic extract of UD can have protective effect on preventing necrosis of CA3 cells of diabetic rat hippocampus.
Keywords
Endurance Exercise
Urtica dioica
Necrotic
Hippocampus
Diabetes
Subjects
  1. Saravia FE, Beauquis J, Revsin Y, Homo-Delarche F, de Kloet ER, De Nicola AF. Hippocampal neuropathology of diabetes mellitus is relieved by estrogen treatment. Cellular and molecular neurobiology. 2006;26(4-6):941-55.
  2. den Heijer T, Vermeer S, Van Dijk E, Prins N, Koudstaal PJ, Hofman A, et al. Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia. 2003;46(12):1604-10.
  3. Beauquis J, Saravia F, Coulaud J, Roig P, Dardenne M, Homo-Delarche F, et al. Prominently decreased hippocampal neurogenesis in a spontaneous model of type 1 diabetes, the nonobese diabetic mouse. Experimental neurology. 2008;210(2):359-67.
  4. Magariños AM, McEwen BS. Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. PNAS. 2000;97(20):11056-61.
  5. Valastro B, Cossette J, Lavoie N, Gagnon S, Trudeau F, Massicotte G. Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus. Diabetologia. 2002;45(5):642-50.
  6. Zhao W-Q, Chen H, Quon MJ, Alkon DL. Insulin and the insulin receptor in experimental models of learning and memory. European journal of pharmacology. 2004;490(1-3):71-81.
  7. Sima AA, Li Z-g, Zhang W. The insulin-like growth factor system and neurological complications in diabetes. Journal of Diabetes Research. 2003;4(4):235-56.
  8. Robinson R, Krishnakumar A, Paulose C. Enhanced dopamine D1 and D2 receptor gene expression in the hippocampus of hypoglycaemic and diabetic rats. Cellular and molecular neurobiology. 2009;29(3):365-72.
  9. Aragno M, Mastrocola R, Medana C, Restivo F, Catalano MG, Pons N, et al. Up-regulation of advanced glycated products receptors in the brain of diabetic rats is prevented by antioxidant treatment. Endocrinology. 2005;146(12):5561-7.
  10. Orlovsky M, Spiga F, Lebed Y, Skibo G, Lightman S. Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes. Neurophysiology. 2007;39(6):435-8.
  11. Lebed YV, Orlovsky M, Lushnikova I, Skibo G. Neurodegenerative changes in the hippocampus within the early period of experimental diabetes mellitus. Neurophysiology. 2008;40(1):26-33.
  12. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrine reviews. 2002;23(5):599-622.
  13. Guzman SJ, Schlögl A, Frotscher M, Jonas P. Synaptic mechanisms of pattern completion in the hippocampal CA3 network. Science. 2016;353(6304):1117-23.
  14. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress− activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes. 2003;52(1):1-8.
  15. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. International journal of physiology, pathophysiology and pharmacology. 2019;11(3):45-63.
  16. Shamsaei N, Abdi H, Shamsi M. The Effect of a continuous training on necrosis and apoptosis changes in the hippocampus of diabetic rats. SJIMU. 2017;25(1):1-11.
  17. Cotman CW, Berchtold NC, Christie L-A. Exercise builds brain health: key roles of growth factor cascades and inflammation. TINS. 2007;30(9):464-72.
  18. de Senna PN, Ilha J, do Nascimento PS, Leite MC, Paim MF, Gonçalves CA, et al. Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats. Metabolic brain disease. 2011;26(4):269-279.
  19. Voulgari C, Papadogiannis D, Tentolouris N. Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies. Vascular health and risk management. 2010;6:883-903.
  20. Teixeira-Lemos E, Nunes S, Teixeira F, Reis F. Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovascular diabetology. 2011;10(1):1-15.
  21. Gharakhanlou R, Chadan S, Gardiner P. Increased activity in the form of endurance training increases calcitonin gene-related peptide content in lumbar motoneuron cell bodies and in sciatic nerve in the rat. Neuroscience. 1999;89(4):1229-39.
  22. Mazzola PN, Terra M, Rosa AP, Mescka CP, Moraes TB, Piccoli B, et al. Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic rats. Metabolic brain disease. 2011;26(4):291-297.
  23. Kavalalı G, Tuncel H, Göksel S, Hatemi H. Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats. Journal of Ethnopharmacology. 2003;84(2):241-5.
  24. Yener Z, Celik I, Ilhan F, Bal R. Effects of Urtica dioica L. seed on lipid peroxidation, antioxidants and liver pathology in aflatoxin-induced tissue injury in rats. FCT. 2009;47(2):418-24.
  25. Patel SS, Udayabanu M. Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy. Neuroscience Letters. 2013;552:114-9.
  26. Oishi N, Nomoto M, Ohkawa N, Saitoh Y, Sano Y, Tsujimura S, et al. Artificial association of memory events by optogenetic stimulation of hippocampal CA3 cell ensembles. Molecular brain. 2019;12(1):1-10.
  27. Cherubini E, Miles RM. The CA3 region of the hippocampus: how is it? What is it for? How does it do it? Frontiers in cellular neuroscience. 2015;9(19):1-3.
  28. Rahmati M, Kazemi A. Various exercise intensities differentially regulate GAP-43 and CAP-1 expression in the rat hippocampus. Gene. 2019;692:185-94.
  29. Rahmati M, Gharakhanlou R, Movahedin M, Mowla SJ, Khazani A, Fouladvand M, et al. Treadmill Training Modifies KIF5B Moter Protein in the STZ-induced Diabetic Rat Spinal Cord and Sciatic Nerve. AIM. 2015;18(2):94-101.
  30. Ahmadi M, Hajihashemi S, Chehrei A, Hosseini N. Therapeutic effects of Urtica dioica methanolic extract on gentamicin induced nephrotoxicity in rats. Koomesh. 2014;15(2):220-31.
  31. Singleton VL, Orthofer R, Lamuela-Raventós RM. [14] Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods in enzymology. 299: Elsevier; 1999. p. 152-78.
  32. Patel SS, Gupta S, Udayabanu M. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice. Metabolic brain disease. 2016;31(3):601-11.
  33. Sharifi AM, Baniasadi S, Jorjani M, Rahimi F, Bakhshayesh M. Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo. Neuroscience letters. 2002;329(1):45-8.
  34. Matsuwaki T, Asakura R, Suzuki M, Yamanouchi K, Nishihara M. Age-dependent changes in progranulin expression in the mouse brain. Journal of Reproduction and Development. 2011;57(1):113-9
  35. Azad N, Rasoolijazi H, Joghataie MT, Soleimani S. Neuroprotective effects of carnosic acid in an experimental model of Alzheimer’s disease in rats. Cell Journal 2011;13(1):39-44.
  36. Gomes R, de Mello M, Caetano F, Sibuya C, Anaruma CA, Rogatto G, et al. Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats. Growth Hormone & IGF Research. 2006;16(5-6):326-31.
  37. Kamaei L, Moghadamnia D. Comparison of Antidiabetic Effects of Aqueous Extract of the Leaves and Fruits of Avicennia Marina in Streptozotocin-induced Diabetic Male Rats. Iranian Journal of Toxicology. 2019;13(2):7-12.
  38. Mehri A, Hasani-Ranjbar S, Larijani B, Abdollahi M. A systematic review of efficacy and safety of Urtica dioica in the treatment of diabetes. IJP. 2011;7(2):161-70.
  39. Song Y, Manson JE, Buring JE, Sesso HD, Liu S. Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. JACN. 2005;24(5):376-84.
  40. Önal S, Timur S, Okutucu B, Zihnioğlu F. Inhibition of α‐glucosidase by aqueous extracts of some potent antidiabetic medicinal herbs. Preparative Biochemistry and Biotechnology. 2005;35(1):29-36.
  41. Golalipour MJ, Khori V. The protective activity of Urtica dioica leaves on blood glucose concentration and beta-cells in streptozotocin-diabetic rats. PJBS 2007;10(8):1200-4.
  42. Reagan LP, Magariños AM, Yee DK, Swzeda LI, Van Bueren A, McCall AL, et al. Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress. Brain research. 2000;862(1-2):292-300.
  43. Teucher T, Obertreis B, Ruttkowski T, Schmitz H. Cytokine secretion in whole blood of healthy subjects following oral administration of Urtica dioica L. plant extract. Arzneimittelforschung. 1996;46(9):906-10.
  44. Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H. Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid. Arzneimittelforschung. 1996;46(1):52-6.
  45. Chevassus H, Mourand I, Molinier N, Lacarelle B, Brun J-F, Petit P. Assessment of single-dose benzodiazepines on insulin secretion, insulin sensitivity and glucose effectiveness in healthy volunteers: a double-blind, placebo-controlled, randomized cross-over trial [ISRCTN08745124]. BMC clinical pharmacology. 2004;4(1):1-10.
  46. Ang E, Wong P, Moochhala S, Ng Y. Neuroprotection associated with running: is it a result of increased endogenous neurotrophic factors? Neuroscience. 2003;118(2):335-45.
  47. Atalay M, Laaksonen DE. Diabetes, oxidative stress and physical exercise. JSSM. 2002;1(1):1-14.
  48. Hong J-H, Kim M-J, Park M-R, Kwag O-G, Lee I-S, Byun BH, et al. Effects of vitamin E on oxidative stress and membrane fluidity in brain of streptozotocin-induced diabetic rats. Clinica chimica acta. 2004;340(1-2):107-15.
  49. Aksu I, Topcu A, Camsari UM, Acikgoz O. Effect of acute and chronic exercise on oxidant–antioxidant equilibrium in rat hippocampus, prefrontal cortex and striatum. Neuroscience letters. 2009;452(3):281-5.
  50. Muller AP, Gnoatto J, Moreira JD, Zimmer ER, Haas CB, Lulhier F, et al. Exercise increases insulin signaling in the hippocampus: physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice. Hippocampus. 2011;21(10):1082-92.
  51. Aguiar Jr AS, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, et al. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mechanisms of ageing and development. 2011;132(11-12):560-7.
  52. Kwak H-B. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil. 2013;9(2):212-219.
  53. Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K. Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. EIR. 2002;8:6-48.

  • Receive Date 27 October 2019
  • Revise Date 16 April 2020
  • Accept Date 04 May 2020