Effects of water training with betaine supplementation on vascular endothelial growth factor and oxidative stress markers in the cerebellum of rats with multiple sclerosis

Moradi, Masoud; Habibi, Abdolhamid; Tabande, MohammadReza; Shakerian, Saeed

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Volume 33, Issue 1 (4-2025)

Journal of Ilam University of Medical Sciences 2025, 33(1): 96-110

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Effects of water training with betaine supplementation on vascular endothelial growth factor and oxidative stress markers in the cerebellum of rats with multiple sclerosis

Masoud Moradi¹

, Abdolhamid Habibi ^*²

, MohammadReza Tabande³

, Saeed Shakerian¹

1- Dept of Sports Physiology, College of Sport Sciences, Shahid Chamran University of Ahvaz, Ahwaz, Iran
2- Dept of Sports Physiology, College of Sport Sciences, Shahid Chamran University of Ahvaz, Ahwaz, Iran , h.habibbi14@gmai.cpm
3- Dept of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahwaz, Iran

Abstract: (167 Views)

Introduction: Inflammatory and autoimmune diseases like multiple sclerosis are linked to immune system gene activation and oxidative stress, with betaine demonstrating anti-inflammatory effects by controlling these gene signaling pathways. The aim of the present study was to investigate the effects of water exercises with betaine supplementation on vascular endothelial growth factor and oxidative stress indices in the cerebellum of rats with multiple sclerosis.
Materials & Methods: A study involving 28 adult male rats, aged 12 weeks, was conducted to study MS. MS was induced using cuprizone for 6 weeks, and the rats were divided into 7 groups. Swimming exercises were performed daily for 6 weeks, and betaine was administered daily in drinking water for 6 weeks. Cerebellar tissue was isolated and endothelial growth factor, malondialdehyde, and superoxide dismutase were measured using ELISA kits. Data analysis was done using SPSS V.22, with one-way analysis of variance and LSD post hoc test at a P<0.05 level.
Results: MS disease causes a decrease in endothelial growth factor and superoxide dismutase levels. The lesion + exercise + betaine group showed a significant increase in the endothelial growth factor, a significant decrease in the malondialdehyde and, a significant increase in the superoxide dismutase variable compared to the lesion group (p ≤ 0.001).
Conclusion: Swimming exercises and betaine supplementation can enhance vascular growth factor indices and oxidative stress in individuals with MS by increasing endothelial growth factors and superoxide dismutase.

Keywords: Multiple Sclerosis, Vascular Endothelial Growth Factor, Superoxide Dismutase, Swimming Exercises in water, Malondialdehyde

Full-Text [PDF 1024 kb] (43 Downloads)

Type of Study: Research | Subject: physiology
Received: 2024/05/15 | Accepted: 2024/10/28 | Published: 2025/04/16

References

1. Mehta BK. New hypotheses on sunlight and the geographic variability of multiple sclerosis prevalence. J Neurol Sci. 2010; 292: 5-10. doi: 10.1016/j.jns.2010.02.004.

2. Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019;26:27-40. doi: 10.1111/ene.13819.

3. Calabrese M, Pitteri M. Cognition and fatigue in multiple sclerosis. In: Deluca, J, Sandroff, BM (eds) Cognition and Behavior in Multiple Sclerosis. Washington, DC: American Psychological Association, 2018, pp. 127-48.

4. Iacobaeus E, Amoudruz P, Strom M, Khademi M, Brundin L, Hillert J, et al. The expression of VEGF-A is down regulated in peripheral blood mononuclear cells of patients with secondary progressive multiple sclerosis. PLoS One. 2011;6: e19138. doi: 10.1371/journal.pone.0019138.

5. Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, et al. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci. 2003;18:2803-12. doi: 10.1111/j.1460-9568.2003.03041.x.

6. Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004;225:11-8. doi: 10.1016/j.jns.2004.06.009.

7. Adamczyk-Sowa M, Sowa P, Pierzchala K, Polaniak R, Labuz-Roszak B. Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapyin multiple sclerosis patients. J Physiol Pharmacol 2012; 63: 683-690.

8. Heesen C, Gold SM, Hartmann S, Mladek M, Reer R, Braumann KM, et al. Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. Brain Behav Immun. 2003;17:473-81. doi: 10.1016/s0889-1591(03)00077-1.

9. Yang MT, Lee XX, Huang BH, Chien LH, Wang CC, Chan KH. Effects of Two-Week Betaine Supplementation on Apoptosis, Oxidative Stress, and Aerobic Capacity after Exhaustive Endurance Exercise. Antioxidants (Basel). 2020;9:1189. doi: 10.3390/antiox9121189.

10. Lee EK, Jang EJ, Jung KJ, Kim DH, Yu BP, Chung HY. Betaine attenuates lysophosphatidylcholine-mediated adhesion molecules in aged rat aorta: modulation of the nuclear factor-κB pathway. Exp Gerontol. 2013; 48:517. doi:10.1016/j.exger.2013.02.024.

11. Yan J, Greer JM. NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis. CNS Neurol Disord Drug Targets. 2008;7:536-57. doi: 10.2174/187152708787122941.

12. Kim JY, Yi ES, Lee H, et al. Swimming Exercise Ameliorates Symptoms of MOG-Induced Experimental Autoimmune Encephalomyelitis by Inhibiting Inflammation and Demyelination in Rats. Int Neurourol J. 2020;24(Suppl 1):S39-S47. doi:10.5213/inj.2040156.078.

13. Xie Y, Li Z, Wang Y, Xue X, Ma W, Zhang Y, et al. Effects of moderate- versus high- intensity swimming training on inflammatory and CD4+T cell subset profiles in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2019;328:60-7. doi: 10.1016/j.jneuroim.2018.12.005.

14. Hong JH, Kim MJ, Park MR, Kwag OG, Lee IS, Byun BH, et al. Effects of Vitamin E on Oxidative Stress and Membrane Fluidity in Brain of Streptozotocin-Induced Diabetic Rats. Clin Chim Acta. 2014; 340: 107-15. doi: 10.1016/j.cccn.2003.10.003.

15. Juri MC, Rodriguez O, Obese JA. The Pathophysiological Basis of Sensory Disturbances inParkinson's Disease. J NeurolSci. 2010; 289: 60-5. doi: 10.1016/j.jns.2009.08.018.

16. Zimmermann J, Emrich M, Krauthausen M, Saxe S, Nitsch L, Heneka MT, et al. IL-17A Promotes Granulocyte Infiltration, Myelin Loss, Microglia Activation, and Behavioral Deficits During Cuprizone-Induced Demyelination. Mol Neurobiol. 2017;55 :946-57. doi: 10.1007/s12035-016- 0368-3.

17. Razavinasab M, Shamsizadeh A, ShabaniM, NazeriM, AllahtavakoliM, Asadi-ShekaariM, et al. Pharmacologicalblockade of TRPV1 receptors modulates the effects of 6-OHDA on motor and cognitive functions in a rat model of Parkinson's disease. Fundam Clin Pharmacol. 2013;27:632-40. doi: 10.1111/fcp.12015.

18. Singhal NK, Sternbach S, Fleming S, Alkhayer K, Shelestak J, Popescu D, et al. Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis. Epigenetics. 2020;15:871-86. doi: 10.1080/15592294.2020.1735075.

19. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic Growth Factor Expression In Rat Skeletal Muscle In Response To Exercise Training. Am J Physiol Heart Circ Physiol. 2013; 284: H1668-78. doi: 10.1152/ajpheart.00743.2002.

20. Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, et al. Exercise-Induced Overexpression Of Angiogenic Factors And Reduction Of Ischemia/Reperfusion Injury In Stroke. Curr Neurovasc Res. 2014; 1: 411-20. doi: 10.2174/1567202043361875.

21. Gustafsson T, Knutsson A, Puntschart A, Kaijser L, Nordqvist SA-C, Sundberg C, et al. Increased expression of vascular endothelial. Pflugers Arch. 2012; 444:752-9. doi: 10.1007/s00424-002-0845-6.

22. Hashemvarzi SA, Heidarian Poor A. Preconditioning Effect of Aerobic Exercise with D3 Vitamin Consumption on VEGF levels in the 6-OHDA Lesioned Parkinson's Disease Rat Model. Sport Physiol. 2016; 8: 129-42. doi: 10.22089/spj.2016.774.

23. Czarkowska-Paczek B, Zendzian- Piotrowska M, Bartlomiejczyk I, Przybylski J, Gorski J. The Influence Of Physical Exercise On The Generation Of TGF-Β1, PDGF-AA, And VEGF-A In Adipose Tissue. Eur j J Appl Physiol. 2011; 111: 875-81. doi: 10.1007/s00421-010-1693-2.

24. Yang MT, Lee XX, Huang BH, Chien LH, Wang CC, Chan KH. Effects of Two-Week Betaine Supplementation on Apoptosis, Oxidative Stress, and Aerobic Capacity after Exhaustive Endurance Exercise. Antioxidants (Basel). 2020;9:1189. doi: 10.3390/antiox9121189.

25. Ebrahimi L, Haghighi S, Hosseini Kakhki A, Nikkhah A. the effect of eight weeks of combined exercise (aerobic-resistance) on the activity of antioxidant enzymes in women with multiple sclerosis with a regular sexual cycle. Basic Clin Res J. 2018; 26. (persian)

26. Chang CK, Huang HY, Tseng HF, Hsuuw YD, Tso TK. Interaction Of Vitamine And Exercise Training On Oxidative Stress And Antioxidant Enzyme Activities In Rat Skeletal Muscles. J Nutr Biochem. 2007; 18: 39-45. doi: 10.1016/j.jnutbio.2006.02.007.

27. Moradi S, Habibi A, Tabande M, shakerian S. Comparing the effect of 6 weeks of continuous and interval aerobic training on vascular endothelial growth factor and superoxide dismutase enzyme in hippocampus of male rats of Parkinson's model. J Shahid Sadoughi Univ Med Sci. 2019; 27: 1302-12. doi: 10.18502/ssu.v27i3.1185.

28. Devi SA, Kiran TR. Regional responses in antioxidant system to exercise training and dietary vitamin E in aging rat brain. Neurobiol Aging. 2014; 25: 501-8. doi: 10.1016/S0197-4580(03)00112-X.

29. Pinho RA, Andrades ME, Oliveira MR, Pirola AC, Zago MS, Silveira PC, et al. Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise. Cell Biol Int. 2006;30:848-53. doi: 10.1016/j.cellbi.2006.03.011.

30. Moradi S, Habibi AH, Shakerian S, Tabande MR. Comparison of the Effect of Continuous and Interval Aerobic Exercises on the Levels of Malondialdehyde, Dopamine and Glutathione Peroxidase in the Hippocampus of Rats with Pseudoparkinsonism. Jundishapur Sci Med J. 2020; 19:187-201.

31. Acikgoz O, Aksu I, Topcu A, Kayatekin B. MAcute exhaustive exercise does not alter lipid peroxidation levels and antioxidant enzyme activities in rat hippocampus,prefrontal cortex and striatum. Neurosci Lett. 2006; 406: 148-51. doi: 10.1016/j.neulet.2006.07.034.

32. Lekhi C, Gupta PH, Singh B. Influence of exercise on oxidant stress products in elite Indian cyclists. Br J Sports Med. 2007;41: 691-3. doi: 10.1136/bjsm.2007.037663.

33. Radak Z, Told A, Szabo Z, Siamilis S, Nyakas C, Silye G, et al. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem Int. 2006;49:387-92. doi: 10.1016/j.neuint.2006.02.004.

34. Tajiri N, Yasuhara T, Shingo T, Kondo A, Yuan W, Kadota T, et al. Exercise exerts neuroprotective effects on Parkinson's diseases model of rats. Brain Res. 2010;1310:200-7. doi: 10.1016/j.brainres.2009.10.075.

35. Radovanovic D, Jakovljevic V, Cvetkovic T, Ignjatovic A, Veselinovic N, Dondur S. Effects of different exercise program on blood markers of oxidative stress in young women. Fiziologia. 2008; 18: 16-20.

36. Knopman D and Patterson M: An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients. Alzheimer Dis Assoc Disord. 2001;15:162-5.

37. Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004;225:11-8. doi: 10.1016/j.jns.2004.06.009.

38. Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, et al. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci. 2003;18:2803-12. doi: 10.1111/j.1460-9568.2003.03041.x.

39. Adamczyk-Sowa M, Sowa P, Pierzchala K. Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients. J Physiol Pharmacol. 2012;63:683-90.

40. Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, et al. Effects of exercise on irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol. 2016; 299: 53-8. doi: 10.1016/j.jneuroim.2016.08.007.

41. zkul C, Guclu-Gunduz A, Irkec C, Fidan I, Aydin Y, Ozkan T, et al. Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis. J Neuroimmunol. 2018; 316:121-9. doi: 10.1016/j.jneuroim.2018.01.002.

42. Ghonimi NAM, Elsharkawi KA, Khyal DSM, Abdelghani AA. Serum malondialdehyde as a lipid peroxidation marker in multiple sclerosis patients and its relation to disease characteristics. Mult Scler Relat Disord. 2021;51:102941. doi: 10.1016/j.msard.2021.102941.

43. Ljubisavljevic S, Stojanovic I, Vojinovic S, Stojanov D, Stojanovic S, Cvetkovic T, et al. The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced protein oxidation products and total thiol content in plasma and CSF. Neurochem Int. 2013;62:988-97. doi: 10.1016/j.neuint.2013.02.025.

44. Rohrig M. Physical Therapy in Multiple Sclerosis. Clin Bull Natl Mult Scler Soc. 2020; 1-16.

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Moradi M, Habibi A, Tabande M, Shakerian S. Effects of water training with betaine supplementation on vascular endothelial growth factor and oxidative stress markers in the cerebellum of rats with multiple sclerosis. J. Ilam Uni. Med. Sci. 2025; 33 (1) :96-110
URL: http://sjimu.medilam.ac.ir/article-1-8289-en.html

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