Daneshvar Medicine

Daneshvar Medicine

The effectiveness of a course of endurance training and Urtica dioica hydroalcoholic extract on the stereological changes of the capillaries of the hippocampal tissue of diabetic rats

Document Type : Original Article

Authors
Fariba Gudarzi 1
Masoud Rahmati 2
Mehdi Roozbahani 3
Farzaneh Chehlcheraghi 4
Amin Farzaneh Hesari 1
1 Department of Sports Physiology, Sari Branch, Islamic Azad University, Sari, Iran
2 Department of Sports Sciences, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran
3 Motor Behavior Department, Borujerd Branch, Islamic Azad University, Borujerd, Iran
4 Department of Anatomical Sciences, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
10.22070/daneshmed.2024.18697.1445
Abstract
Background and Objective: Diabetes has harmful effects on the vascular structure and angiogenesis of various organs, including the hippocampus. In this regard, this study was designed to investigate the effect of non-pharmacological interventions of endurance training (Ex) and Urtica dioica (UD)  plant hydroalcoholic extract on the stereological changes of the hippocampal capillaries of diabetic rats.
Materials and Methods: 35 Wistar male rats were divided into 5 groups: Healthy control, Diabetes control, Diabetes+Ex, Diabetes+UD, Diabetes+Ex+UD. Diabetes was induced by intraperitoneal injection of streptozotocin. The Ex protocol with moderate intensity and daily gavage of UD hydroalcoholic extract was implemented for six weeks. 48-h after the last session, the rats was sacrificed, and then the hippocampal tissue was removed and placed in 10% formalin for hematoxylin-eosin staining. The stereological changes of the hippocampal tissue were investigated in the parameters of the number of vascular sections, length, volume and area of capillaries. Data analysis was done using repeated measures ANOVA tests for blood glucose variable and Kruskal-Wallis test for stereological studies of hippocampal tissue.
Results: Diabetes caused a significant decrease in the number of vascular sections, length, volume and area of hippocampal capillaries (P<0.001). Thus, all stereological parameters in the combined group of Ex+UD were better than the groups that implemented only one of the interventions (P<0.05). The changes of Ex and UD groups in stereological parameters of hippocampal tissue after 6 weeks were not significant.
Conclusion: The results obtained in  combination effectiveness of Ex and UD on the stereological parameters of the hippocampal tissue of diabetic rats promise to improve the health of the vessels and angiogenesis of the hippocampal tissue by changing the lifestyle of diabetic people.
Keywords
Diabetes
Exercise training
Urtica dioica
Hippocampus
Vascular sections
Capillary
Subjects
  1. Taylor SL, Trudeau D, Arnold B, Wang J, Gerrow K, Summerfeldt K, et al. VEGF can protect against blood brain barrier dysfunction, dendritic spine loss and spatial memory impairment in an experimental model of diabetes. Neurobiology of Disease 2015;78: 1-11.
  2. Li X, Yin Q, Han X, Zhang H, Wang F, Ma J, et al. Dynamic expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor beta (PDGFRβ) in diabetic brain contributes to cognitive dysfunction. Brain Research Bulletin 2021;175:99-106.
  3. Yin Q, Ma J, Han X, Zhang H, Wang F, Zhuang P, et al. Spatiotemporal variations of vascular endothelial growth factor in the brain of diabetic cognitive impairment. Pharmacological Research 2021;163:105234.
  4. Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Medicinal Research Reviews 2003;23(2):117-45.
  5. Vafaei-Nezhad S, Vafaei-Nezhad M, Shadi M, Ezi S. The Impact of Diabetes on Hippocampus. Hippocampus-Cytoarchitecture and Diseases 2021. DOI: 10.5772/intechopen.99895.
  6. Zhao Y, Liu J, Li J, Zhao F, Du S, Wang Y, et al. Changes in hippocampal capillaries in transgenic type 2 diabetic mice: A stereological investigation. The Anatomical Record 2021;304(5):1071-1083.
  7. Nelson PT, Smith CD, Abner EA, Schmitt FA, Scheff SW, Davis GJ , et al. Human cerebral neuropathology of Type 2 diabetes mellitus. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2009;1792(5):454-469.
  8. Van Bussel FC, Backes WH, Hofman PA, van Oostenbrugge RJ, Kessels AG, van Boxtel MP, et al. On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes. Diabetes Care 2015;38(5):876-882.
  9. Van den Berg E, Kessels R, Kappelle L, De Haan E, Biessels GJ. Type 2 diabetes, cognitive function and dementia: vascular and metabolic determinants. Timely Topics in Medicine Cardiovascular Diseases 2007;11:E7-E.
  10. Zacchigna S, Lambrechts D, Carmeliet P. Neurovascular signalling defects in neurodegeneration. Nature Reviews Neuroscience 2008;9(3):169-181.
  11. Chen L, Zhou C, Tan C, Wang F, Gao Y, Huang C, et al. Stereological study on the positive effect of running exercise on the capillaries in the hippocampus in a depression model. Frontiers in Neuroanatomy 2017;11:93.
  12. Lee C-B, Baek S-S. Impact of exercise on hippocampal neurogenesis in hyperglycemic diabetes. Journal of Exercise Rehabilitation 2020;16(2):115.
  13. Nunley KA, Leckie RL, Orchard TJ, Costacou T, Aizenstein HJ, Jennings JR, et al. Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes. Neurology 2017;88(16):1564-1570.
  14. Shamsaei N, Abdi H, Shamsi M. The Effect of a Continuous Training on Necrosis and Apoptosis Changes in the Hippocampus of Diabetic Rats. Journal of Ilam University of Medical Sciences 2017;25(1):1-11.
  15. 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.
  16. 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):12.
  17. Woodward M, Gicas K, Warburton D, White R, Rauscher A, Leonova O, et al. Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia. Schizophrenia Research 2018;202:158-165.
  18. Green DJ, Smith KJ. Effects of exercise on vascular function, structure, and health in humans. Cold Spring Harbor Perspectives in Medicine 2018;8(4):a029819.
  19. Kavalalı G, Tuncel H, Göksel S, Hatemi H. Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats. Journal of Ethnopharmacology 2003;84(2):241-245.
  20. 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.
  21. Keshvari M, Rahmati M, Mirnasouri R, Chehelcheraghi F. Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats. Journal of Ethnopharmacology 2020;256:112801.
  22. Rahmati M, Kazemi A. Various exercise intensities differentially regulate GAP-43 and CAP-1 expression in the rat hippocampus. Gene 2019;692:185-194.
  23. Rahmati M, Keshvari M, Mirnasouri R, Chehelcheraghi F. Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats. Biomedicine & Pharmacotherapy 2021;139:111577.
  24. Habibi M, Chehelcheraghi F. Effect of Bone Marrow Mesenchymal Stem Cell Sheets on Skin Capillary Parameters in a diabetic wound model: A Novel Preliminary Study. Iranian Biomedical Journal 2021;25(5):334.
  25. Mathieu C, Chevrier A, Lascau-Coman V, Rivard G, Hoemann C. Stereological analysis of subchondral angiogenesis induced by chitosan and coagulation factors in microdrilled articular cartilage defects. Osteoarthritis and Cartilage 2013;21(6):849-859.
  26. Ho N, Sommers MS, Lucki I. Effects of diabetes on hippocampal neurogenesis: links to cognition and depression. Neuroscience & Biobehavioral Reviews 2013;37(8):1346-1362.
  27. Ünver Saraydin S, Özdenoglu Kutlu B, Saraydın D. Effects of diabetes on apoptosis and mitosis in rat hippocampus. Biotechnic & Histochemistry 2021;96(6):460-467.
  28. Farhadi A, Vosough M, Zhang J-S, Tahamtani Y, Shahpasand K. A possible neurodegeneration mechanism triggered by diabetes. Trends in Endocrinology & Metabolism 2019;30(10):692-700.
  29. Verma N, Rastogi S. Neurodegeneration in Diabetes Mellitus: An Overview. Antioxidants and Functional Foods for Neurodegenerative Disorders 2021:11-7.
  30. Kirmaz C, Ozbilgin K, Yuksel H, Bayrak P, Unlu H, Giray G, et al. Increased expression of angiogenic markers in patients with seasonal allergic rhinitis. European Cytokine Network 2004;15(4):317-322.
  31. Delbin MA, Trask AJ. The diabetic vasculature: physiological mechanisms of dysfunction and influence of aerobic exercise training in animal models. Life sciences 2014;102(1):1-9.
  32. Yuan T-F, Barbosa Ferreira Rocha N, Paes F, Arias-Carrión O, Machado S, Souza de Sá Filho A. Neural mechanism of exercise: Neurovascular responses to exercise. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 2015;14(10):1304-1306.
  33. SS H. The effect of exercise on reelin level in the hippocampus of diabetic rats. Bratislava Medical Journal/Bratislavske Lekarske Listy 2020;121(6).
  34. Rahbar S, Naimi SS, RezaSoltani A, Rahimi A, Baghban AA, Noori A, et al. Changes in vascular structure in diabetic patients after 8 weeks aerobic physical exercise: A randomized controlled trial. International Journal of Diabetes in Developing Countries 2018;38:202-208.
  35. Mayhan WG, Arrick DM, Patel KP, Sun H. Exercise training normalizes impaired NOS-dependent responses of cerebral arterioles in type 1 diabetic rats. American Journal of Physiology-Heart and Circulatory Physiology 2011;300(3):H1013-H20.
  36. Wang S, Qi Y, Yu L, Zhang L, Chao F, Huang W, et al. Endogenous nitric oxide regulates blood vessel growth factors, capillaries in the cortex, and memory retention in Sprague-Dawley rats. American Journal of Translational Research 2016;8(12):5271.
  37. Sonntag WE, Lynch C, Thornton P, Khan A, Bennett S, Ingram R. The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. The Journal of Anatomy 2000;197(4):575-585.
  38. Sonntag WE, Lynch CD, Cooney PT, Hutchins PM. Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology 1997;138(8):3515-3520.
  39. Sundari LPR, Ar NLKA. Regular Physical Exercise Increase of Growth Hormone (GH) and Insulin-Like Growth Factor-1(IGF-1) Activity in Elderly Improve the Aging Process and Quality of Life: A Mini Review. Biomedical and Pharmacology Journal 2022;15(2):883-90.
  40. Lee HJ. Alteration of Angiogenic Gene Expression in Heart, Muscle and Adipose Tissue by Exercise. Exercise Science 2018;27(1):1-14.
  41. Evans WS, Sapp RM, Kim KI, Heilman JM, Hagberg J, Prior SJ. Effects of exercise training on the paracrine function of circulating angiogenic cells. International Journal of Sports Medicine 2021;42(12):1047-1057.
  42. Ghahramani M, Majd ZR. The Effect of Physical Activity on VEGF and HIF-1 Signaling. Journal of Clinical Research in Paramedical Sciences 2020;9(2).
  43. Mota MM, Silva TLTBd, Barreto AS, Fontes MT, Oliveira ACCd, Santos MRVd. Treinamento aeróbio previne alterações na vasodilatação dependente do endotélio em ratos diabéticos. Revista da Educação Física/UEM 2013;24:423-432.
  44. Kim Y-S, Secher N, Van Lieshout JJ. Resistance exercise and control of cerebral blood flow in type 2 diabetes. Diabetologia 2008;51:1755-1756.
  45. Lenasi H, Klonizakis M. Assessing the evidence: exploring the effects of exercise on diabetic microcirculation. Clinical Hemorheology and Microcirculation 2016;64(4):663-678.
  46. Samakar B, Mehri S, Hosseinzadeh H. A review of the effects of Urtica dioica (nettle) in metabolic syndrome. Iranian Journal of Basic Medical Sciences 2022;25(5):543.
  47. 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. Journal of the American College of Nutrition 2005;24(5):376-384.
  48. 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. Arzneimittel-Forschung 1996;46(9):906-910.
  49. Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H. Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid. Arzneimittel-forschung 1996;46(1):52-56.
  50. 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):3.

 

Daneshvar Medicine
Volume 32, Issue 1 - Serial Number 170
March and April 2024
Pages 45-58