Effect of Exercise, MitoQ, and Their Combination on Inflammatory and Gene Expression in Women with Multiple Sclerosis
,
Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. Current treatments aim to manage symptoms and slow disease progression, but there is a need for effective interventions that target underlying disease mechanisms. In this study, we investigated the effects of exercise, MitoQ (a mitochondria-targeted antioxidant), and their combination on the gene expression of various biomarkers associated with MS in postmenopausal and premenopausal women.
We measured interleukin-6 (IL-6) and key molecular pathways involved in MS pathogenesis, including suppressor of mother against decapentaplegic 2 (SMAD2), signal transducer and activator of transcription 1 (STAT1), and transforming growth factor beta (TGF-β) using real-time polymerase chain reaction.
All interventions significantly lowered IL-6 levels and STAT1, especially in premenopausal women. Also, both exercise and MitoQ led to a significant increase in the SMAD2 and TGF-β expression, with a more pronounced effect on premenopausal women. Noteworthy, the effectiveness of the combination of exercise and MitoQ was considerably higher than each one alone.
These findings suggest that exercise and MitoQ, either alone or combined, can modulate various biological pathways implicated in MS pathogenesis.
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2. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS. Mult Scler J Exp Transl Clin. 2020;26(14):1816-21.
3. Zamanzadeh Z, Ahangari G, Ataei M, Pouragahi S, Nabavi SM, Sadeghi M, Sanati MH. Association of new putative epitopes of myelin proteolipid protein (58-74) with pathogenesis of multiple sclerosis. Iran J Allergy Asthma Immunol. 2016:394-402.
4. Rajizadeh MA, Sheibani V, Bejeshk MA, Mohtashami Borzadaran F, Saghari H, et al. The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide. Int J Neurosci. 2019;129(12):1166-78.5. Laribi B, Sahraian MA, Shekarabi M, Emamnejad R, Marzban M, Sadaghiani S, et al. Characterization of CD4+ and CD8+ T cell subsets and interferon regulatory factor 4 (IRF4) in MS patients treated with Fingolimod (FTY-720): a follow-up study. Iran J Allergy Asthma Immunol. 2018:346-60.
6. Pukoli D, Vécsei L. Smouldering lesion in MS: Microglia, lymphocytes and pathobiochemical mechanisms. Int J Mol Sci. 2023;24(16):12631.
7. Bridge F, Butzkueven H, Van der Walt A, Jokubaitis VG. The impact of menopause on multiple sclerosis. Autoimmun Rev . 2023;22(8):103363.
8. Manoochehrabadi S, Arsang-Jang S, Mazdeh M, Inoko H, Sayad A, Taheri M. Analysis of STAT1, STAT2 and STAT3 mRNA expression levels in the blood of patients with multiple sclerosis. Hum Antibodies. 2019;27(2):91-8.
9. Stampanoni Bassi M, Iezzi E, Drulovic J, Pekmezovic T, Gilio L, Furlan R, et al. IL-6 in the cerebrospinal fluid signals disease activity in multiple sclerosis. Front Cell Neurosci. 2020;14:120.
10. Schönrock LM, Gawlowski G, Brück W. Interleukin-6 expression in human multiple sclerosis lesions. Neurosci Lett. 2000;294(1):45-8.
11. Rajizadeh MA, Nematollahi MH, Jafari E, Bejeshk MA, Mehrabani M, Rostamzadeh F, et al. Formulation and evaluation of the anti-inflammatory, anti-oxidative, and anti-remodelling effects of the niosomal myrtenol on the lungs of asthmatic rats. Iran J Allergy Asthma Immunol. 2023.
12. Heldin C-H, Moustakas A. Role of Smads in TGF-β signaling. Cell Tissue Res. 2012;347(1):21-36.
13. Meoli EM, Oh U, Grant CW, Jacobson S. TGF-β signaling is altered in the peripheral blood of subjects with multiple sclerosis. J Neuroimmunol. 2011;230(1-2):164-8.
14. Esmaeilzadeh A, Mohammadi V, Elahi R. Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches. Mol Biol Rep. 2023;50(7):6121-31.
15. Raji-Amirhasani A, Khaksari M, Shahrokhi N, Soltani Z, Nazari-Robati M, Mahani FD, et al. Comparison of the effects of different dietary regimens on susceptibility to experimental acute kidney injury: The roles of SIRT1 and TGF-β1. Nutr J. 2022;96:111588.
16. Miyazono K. TGF-β signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11(1-2):15-22.
17. Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Jazayeri S, Reza Gohari M. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with relapsing–remitting multiple sclerosis. Int J Neurosci. 2013;123(11):776-82.
18. Fields M, Marcuzzi A, Gonelli A, Celeghini C, Maximova N, Rimondi E. Mitochondria-targeted antioxidants, an innovative class of antioxidant compounds for neurodegenerative diseases: perspectives and limitations. Int J Mol Sci. 2023;24(4):3739.
19. Modi HR, Musyaju S, Ratcliffe M, Shear DA, Scultetus AH, Pandya JD. Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury. Antioxidants (Basel). 2024;13(3):303.
20. Piscianz E, Tesser A, Rimondi E, Melloni E, Celeghini C, Marcuzzi A. MitoQ is able to modulate apoptosis and inflammation. Int J Mol Sci. 2021;22(9):4753.
21. Lu Y, Wiltshire HD, Baker JS, Wang Q. Effects of high intensity exercise on oxidative stress and antioxidant status in untrained humans: A systematic review. J Biol. 2021;10(12):1272.
22. Zadeh HJ, Roholamini Z, Aminizadeh S, Deh-Ahmadi MA. Endurance training and MitoQ supplementation improve spatial memory, VEGF expression, and neurogenic factors in hippocampal tissue of rats. J Clin Transl Res. 2023;9(1):1.
23. Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16(10):848-56.
24. Rezaeimanesh N, Rafiee P, Saeedi R, Eskandarieh S, Sahraian MA, Khosravian P, et al. Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis. Front Neurol. 2023;14:1126215.
25. Sadeghi Bahmani D, Kesselring J, Papadimitriou M, Bansi J, Pühse U, Gerber M, et al. In patients with multiple sclerosis, both objective and subjective sleep, depression, fatigue, and paresthesia improved after 3 weeks of regular exercise. Front Psychiatry. 2019;10:265.
26. Garopoulou V, Meke M, Latsiou E, Papakonstantinou G, Mouzakidis C, Notas K, et al. The efficacy of different Aerobic, Pilates and combined therapeutic exercise protocols to functional capacity, fatigue and quality of life in adults with Multiple Sclerosis: controlled experimental intervention . J Phys Act Nutr Rehabil. 2019.
27. Pham T, MacRae CL, Broome SC, D’souza RF, Narang R, Wang HW, et al. MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men. Eur J Appl Physiol. 2020;120:1657-69.28. Barry A, Cronin O, Ryan AM, Sweeney B, O’Toole O, Allen AP, et al. Impact of short-term cycle ergometer training on quality of life, cognition and depressive symptomatology in multiple sclerosis patients: a pilot study. J Neurol Sci. 2018;39:461-9.
29. Barry A, Cronin O, Ryan AM, Sweeney B, O’Toole O, O’Halloran KD, et al. Cycle ergometer training enhances plasma interleukin-10 in multiple sclerosis. J Neurol Sci. 2019;40:1933-6.
30. Devasahayam AJ, Kelly LP, Williams JB, Moore CS, Ploughman M. Fitness shifts the balance of BDNF and IL-6 from inflammation to repair among people with progressive multiple sclerosis. Biomolecules. 2021;11(4):504.
31. Lozano-Ros A, Martínez-Ginés ML, García-Domínguez JM, Salvador-Martín S, Goicochea-Briceño H, Cuello JP, Meldaña-Rivera A, et al. Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis. Int J Mol Sci. 2023;24(19):14447.
32. Mao P, Manczak M, Shirendeb UP, Reddy PH. MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Biochim Biophys Acta Mol Basis Dis. 2013;1832(12):2322-31.
33. Haidar MA, Shakkour Z, Barsa C, Tabet M, Mekhjian S, Darwish H, et al. Mitoquinone helps combat the neurological, cognitive, and molecular consequences of open head traumatic brain injury at chronic time point. Biomedicine (Taipei). 2022;10(2):250.
34. Ghonimi NA, Elsharkawi KA, Khyal DS, 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.
35. McManus MJ, Murphy MP, Franklin JL. The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's disease. J Nanoneurosci. 2011;31(44):15703-15.
36. Miquel E, Cassina A, Martínez-Palma L, Souza JM, Bolatto C, Rodríguez-Bottero S, et al. Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis. Free Radic Biol Med. 2014;70:204-13.
37. Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, et al. Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med. 2010;49(11):1674-84.
38. Pinho BR, Duarte AI, Canas PM, Moreira PI, Murphy MP, Oliveira JM. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice. Free Radic Biol Med. 2020;146:372-82.
39. Mee-Inta O, Zhao Z-W, Kuo Y-M. Physical exercise inhibits inflammation and microglial activation. Cell J. 2019;8(7):691.
40. Tadayon Zadeh F, Amini H, Habibi S, Shahedi V, Isanejad A, Akbarpour M. The effects of 8-week combined exercise training on inflammatory markers in women with multiple sclerosis. Neurodegener Dis. 2021;20(5-6):212-6.
41. Masoumi-Ardakani Y, Najafipour H, Nasri HR, Aminizadeh S, Jafari SJ, Safi Z. Moderate endurance training and MitoQ improve cardiovascular function, oxidative stress, and inflammation in hypertensive individuals: the role of miR-21 and miR-222: a randomized, double-blind, clinical trial. Yakhteh. 2022;24(10):577.
42. Brooks SV, Vasilaki A, Larkin LM, McArdle A, Jackson MJ. Repeated bouts of aerobic exercise lead to reductions in skeletal muscle free radical generation and nuclear factor κB activation. Physiol J. 2008;586(16):3979-90.
43. Leeuwenburgh C, Heinecke J. Oxidative stress and antioxidants in exercise. Current medicinal chemistry. 2001;8(7):829-38.
44. Jeong J-H, Koo J-H, Yook JS, Cho J-Y, Kang E-B. Neuroprotective benefits of exercise and MitoQ on memory function, mitochondrial dynamics, oxidative stress, and neuroinflammation in D-galactose-induced aging rats. Brain Sci. 2021;11(2):164.
45. Shirvani H, Nikbakht H, Ebrahim K, Gaeini AA. The effects of Coenzyme Q10 supplementation with high intensity intermittent Exercise on serum IL-6 and TNF-α in well-trained soccer players. Eur J Exp Biol. 2012;2(5):1664-167.
46. Nakhzari Khodakheir J, Haghighi A, Hamedinia M, Nikkhah K. The Effects of Combined Exercise Training with Aerobic Dominant and Coenzyme Q10 Supplementation on Serum Levels of IL-10 and TNF-α in Patient with Multiple Sclerosis. Armaghane danesh. 2018;22(6):702-13.in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2019;328:60-7.
48. Zong B, Yu F, Zhang X, Zhao W, Li S, Li L. Mechanisms underlying the beneficial effects of physical exercise on multiple sclerosis: focus on immune cells. Front Immunol. 2023;14:1260663.
49. Ntanasis-Stathopoulos J, Tzanninis J, Philippou A, Koutsilieris M. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact. 2013;13(2):133-46.
50. Holloszy JO. Regulation of mitochondrial biogenesis and GLUT4 expression by exercise. Compr Physiol. 2011;1(2):921-40.
51. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. Physiol J. 2010;588(6):1011-22.
52. Vnukov V, Gutsenko O, Milyutina N, Kornienko I, Ananyan A, Plotnikov A, et al. SkQ1 regulates expression of Nrf2, ARE-controlled genes encoding antioxidant enzymes, and their activity in cerebral cortex under oxidative stress. Biochemistry (Moscow). 2017;82:942-52.
53. Li H, Guo Y, Su W, Zhang H, Wei X, Ma X, Gong S, et al. The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver. Ecotoxicol Environ Saf. 2024;277:116350.
54. Abarca-Zabalía J, García MI, Lozano Ros A, Marín-Jiménez I, Martínez-Ginés ML, López-Cauce B, et al. Differential expression of SMAD genes and S1PR1 on circulating CD4+ T cells in multiple sclerosis and Crohn’s disease. Int J Mol Sci. 2020;21(2):676.
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2. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS. Mult Scler J Exp Transl Clin. 2020;26(14):1816-21.
3. Zamanzadeh Z, Ahangari G, Ataei M, Pouragahi S, Nabavi SM, Sadeghi M, Sanati MH. Association of new putative epitopes of myelin proteolipid protein (58-74) with pathogenesis of multiple sclerosis. Iran J Allergy Asthma Immunol. 2016:394-402.
4. Rajizadeh MA, Sheibani V, Bejeshk MA, Mohtashami Borzadaran F, Saghari H, et al. The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide. Int J Neurosci. 2019;129(12):1166-78.5. Laribi B, Sahraian MA, Shekarabi M, Emamnejad R, Marzban M, Sadaghiani S, et al. Characterization of CD4+ and CD8+ T cell subsets and interferon regulatory factor 4 (IRF4) in MS patients treated with Fingolimod (FTY-720): a follow-up study. Iran J Allergy Asthma Immunol. 2018:346-60.
6. Pukoli D, Vécsei L. Smouldering lesion in MS: Microglia, lymphocytes and pathobiochemical mechanisms. Int J Mol Sci. 2023;24(16):12631.
7. Bridge F, Butzkueven H, Van der Walt A, Jokubaitis VG. The impact of menopause on multiple sclerosis. Autoimmun Rev . 2023;22(8):103363.
8. Manoochehrabadi S, Arsang-Jang S, Mazdeh M, Inoko H, Sayad A, Taheri M. Analysis of STAT1, STAT2 and STAT3 mRNA expression levels in the blood of patients with multiple sclerosis. Hum Antibodies. 2019;27(2):91-8.
9. Stampanoni Bassi M, Iezzi E, Drulovic J, Pekmezovic T, Gilio L, Furlan R, et al. IL-6 in the cerebrospinal fluid signals disease activity in multiple sclerosis. Front Cell Neurosci. 2020;14:120.
10. Schönrock LM, Gawlowski G, Brück W. Interleukin-6 expression in human multiple sclerosis lesions. Neurosci Lett. 2000;294(1):45-8.
11. Rajizadeh MA, Nematollahi MH, Jafari E, Bejeshk MA, Mehrabani M, Rostamzadeh F, et al. Formulation and evaluation of the anti-inflammatory, anti-oxidative, and anti-remodelling effects of the niosomal myrtenol on the lungs of asthmatic rats. Iran J Allergy Asthma Immunol. 2023.
12. Heldin C-H, Moustakas A. Role of Smads in TGF-β signaling. Cell Tissue Res. 2012;347(1):21-36.
13. Meoli EM, Oh U, Grant CW, Jacobson S. TGF-β signaling is altered in the peripheral blood of subjects with multiple sclerosis. J Neuroimmunol. 2011;230(1-2):164-8.
14. Esmaeilzadeh A, Mohammadi V, Elahi R. Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches. Mol Biol Rep. 2023;50(7):6121-31.
15. Raji-Amirhasani A, Khaksari M, Shahrokhi N, Soltani Z, Nazari-Robati M, Mahani FD, et al. Comparison of the effects of different dietary regimens on susceptibility to experimental acute kidney injury: The roles of SIRT1 and TGF-β1. Nutr J. 2022;96:111588.
16. Miyazono K. TGF-β signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11(1-2):15-22.
17. Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Jazayeri S, Reza Gohari M. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with relapsing–remitting multiple sclerosis. Int J Neurosci. 2013;123(11):776-82.
18. Fields M, Marcuzzi A, Gonelli A, Celeghini C, Maximova N, Rimondi E. Mitochondria-targeted antioxidants, an innovative class of antioxidant compounds for neurodegenerative diseases: perspectives and limitations. Int J Mol Sci. 2023;24(4):3739.
19. Modi HR, Musyaju S, Ratcliffe M, Shear DA, Scultetus AH, Pandya JD. Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury. Antioxidants (Basel). 2024;13(3):303.
20. Piscianz E, Tesser A, Rimondi E, Melloni E, Celeghini C, Marcuzzi A. MitoQ is able to modulate apoptosis and inflammation. Int J Mol Sci. 2021;22(9):4753.
21. Lu Y, Wiltshire HD, Baker JS, Wang Q. Effects of high intensity exercise on oxidative stress and antioxidant status in untrained humans: A systematic review. J Biol. 2021;10(12):1272.
22. Zadeh HJ, Roholamini Z, Aminizadeh S, Deh-Ahmadi MA. Endurance training and MitoQ supplementation improve spatial memory, VEGF expression, and neurogenic factors in hippocampal tissue of rats. J Clin Transl Res. 2023;9(1):1.
23. Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16(10):848-56.
24. Rezaeimanesh N, Rafiee P, Saeedi R, Eskandarieh S, Sahraian MA, Khosravian P, et al. Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis. Front Neurol. 2023;14:1126215.
25. Sadeghi Bahmani D, Kesselring J, Papadimitriou M, Bansi J, Pühse U, Gerber M, et al. In patients with multiple sclerosis, both objective and subjective sleep, depression, fatigue, and paresthesia improved after 3 weeks of regular exercise. Front Psychiatry. 2019;10:265.
26. Garopoulou V, Meke M, Latsiou E, Papakonstantinou G, Mouzakidis C, Notas K, et al. The efficacy of different Aerobic, Pilates and combined therapeutic exercise protocols to functional capacity, fatigue and quality of life in adults with Multiple Sclerosis: controlled experimental intervention . J Phys Act Nutr Rehabil. 2019.
27. Pham T, MacRae CL, Broome SC, D’souza RF, Narang R, Wang HW, et al. MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men. Eur J Appl Physiol. 2020;120:1657-69.28. Barry A, Cronin O, Ryan AM, Sweeney B, O’Toole O, Allen AP, et al. Impact of short-term cycle ergometer training on quality of life, cognition and depressive symptomatology in multiple sclerosis patients: a pilot study. J Neurol Sci. 2018;39:461-9.
29. Barry A, Cronin O, Ryan AM, Sweeney B, O’Toole O, O’Halloran KD, et al. Cycle ergometer training enhances plasma interleukin-10 in multiple sclerosis. J Neurol Sci. 2019;40:1933-6.
30. Devasahayam AJ, Kelly LP, Williams JB, Moore CS, Ploughman M. Fitness shifts the balance of BDNF and IL-6 from inflammation to repair among people with progressive multiple sclerosis. Biomolecules. 2021;11(4):504.
31. Lozano-Ros A, Martínez-Ginés ML, García-Domínguez JM, Salvador-Martín S, Goicochea-Briceño H, Cuello JP, Meldaña-Rivera A, et al. Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis. Int J Mol Sci. 2023;24(19):14447.
32. Mao P, Manczak M, Shirendeb UP, Reddy PH. MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Biochim Biophys Acta Mol Basis Dis. 2013;1832(12):2322-31.
33. Haidar MA, Shakkour Z, Barsa C, Tabet M, Mekhjian S, Darwish H, et al. Mitoquinone helps combat the neurological, cognitive, and molecular consequences of open head traumatic brain injury at chronic time point. Biomedicine (Taipei). 2022;10(2):250.
34. Ghonimi NA, Elsharkawi KA, Khyal DS, 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.
35. McManus MJ, Murphy MP, Franklin JL. The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's disease. J Nanoneurosci. 2011;31(44):15703-15.
36. Miquel E, Cassina A, Martínez-Palma L, Souza JM, Bolatto C, Rodríguez-Bottero S, et al. Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis. Free Radic Biol Med. 2014;70:204-13.
37. Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, et al. Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med. 2010;49(11):1674-84.
38. Pinho BR, Duarte AI, Canas PM, Moreira PI, Murphy MP, Oliveira JM. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice. Free Radic Biol Med. 2020;146:372-82.
39. Mee-Inta O, Zhao Z-W, Kuo Y-M. Physical exercise inhibits inflammation and microglial activation. Cell J. 2019;8(7):691.
40. Tadayon Zadeh F, Amini H, Habibi S, Shahedi V, Isanejad A, Akbarpour M. The effects of 8-week combined exercise training on inflammatory markers in women with multiple sclerosis. Neurodegener Dis. 2021;20(5-6):212-6.
41. Masoumi-Ardakani Y, Najafipour H, Nasri HR, Aminizadeh S, Jafari SJ, Safi Z. Moderate endurance training and MitoQ improve cardiovascular function, oxidative stress, and inflammation in hypertensive individuals: the role of miR-21 and miR-222: a randomized, double-blind, clinical trial. Yakhteh. 2022;24(10):577.
42. Brooks SV, Vasilaki A, Larkin LM, McArdle A, Jackson MJ. Repeated bouts of aerobic exercise lead to reductions in skeletal muscle free radical generation and nuclear factor κB activation. Physiol J. 2008;586(16):3979-90.
43. Leeuwenburgh C, Heinecke J. Oxidative stress and antioxidants in exercise. Current medicinal chemistry. 2001;8(7):829-38.
44. Jeong J-H, Koo J-H, Yook JS, Cho J-Y, Kang E-B. Neuroprotective benefits of exercise and MitoQ on memory function, mitochondrial dynamics, oxidative stress, and neuroinflammation in D-galactose-induced aging rats. Brain Sci. 2021;11(2):164.
45. Shirvani H, Nikbakht H, Ebrahim K, Gaeini AA. The effects of Coenzyme Q10 supplementation with high intensity intermittent Exercise on serum IL-6 and TNF-α in well-trained soccer players. Eur J Exp Biol. 2012;2(5):1664-167.
46. Nakhzari Khodakheir J, Haghighi A, Hamedinia M, Nikkhah K. The Effects of Combined Exercise Training with Aerobic Dominant and Coenzyme Q10 Supplementation on Serum Levels of IL-10 and TNF-α in Patient with Multiple Sclerosis. Armaghane danesh. 2018;22(6):702-13.in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2019;328:60-7.
48. Zong B, Yu F, Zhang X, Zhao W, Li S, Li L. Mechanisms underlying the beneficial effects of physical exercise on multiple sclerosis: focus on immune cells. Front Immunol. 2023;14:1260663.
49. Ntanasis-Stathopoulos J, Tzanninis J, Philippou A, Koutsilieris M. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact. 2013;13(2):133-46.
50. Holloszy JO. Regulation of mitochondrial biogenesis and GLUT4 expression by exercise. Compr Physiol. 2011;1(2):921-40.
51. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. Physiol J. 2010;588(6):1011-22.
52. Vnukov V, Gutsenko O, Milyutina N, Kornienko I, Ananyan A, Plotnikov A, et al. SkQ1 regulates expression of Nrf2, ARE-controlled genes encoding antioxidant enzymes, and their activity in cerebral cortex under oxidative stress. Biochemistry (Moscow). 2017;82:942-52.
53. Li H, Guo Y, Su W, Zhang H, Wei X, Ma X, Gong S, et al. The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver. Ecotoxicol Environ Saf. 2024;277:116350.
54. Abarca-Zabalía J, García MI, Lozano Ros A, Marín-Jiménez I, Martínez-Ginés ML, López-Cauce B, et al. Differential expression of SMAD genes and S1PR1 on circulating CD4+ T cells in multiple sclerosis and Crohn’s disease. Int J Mol Sci. 2020;21(2):676.
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| Files | ||
| Issue | Vol 23 No 6 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i6.17377 | |
| Keywords | ||
| Multiple sclerosis Exercise training MitoQ Inflammation | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Alifarsangi A, Khaksari M, Seifaddini R. Effect of Exercise, MitoQ, and Their Combination on Inflammatory and Gene Expression in Women with Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2024;23(6):676-687.
