Volume 31, Issue 6 (September 2020)
Studies in Medical Sciences 2020, 31(6): 485-498 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Jafari Khataylou Y, Ahmadiafshar S. THE EFFECT OF TROXEROTIN ON PRO-INFLAMMATORY CYTOKINES AND LYMPHOCYTE PROLIFERATION IN AN ANIMAL MODEL OF AUTOIMMUNE EXPERIMENTAL ENCEPHALOMYELITIS. Studies in Medical Sciences 2020; 31 (6) :485-498
URL: http://umj.umsu.ac.ir/article-1-5122-en.html
URL: http://umj.umsu.ac.ir/article-1-5122-en.html
Candidate for phd in Immunology Department of Microbiology, Faculty of veterinary medicine, University of Urmia, Urmia, Iran (Corresponding Author) , afsharnegin92@gmail.com
Abstract: (2372 Views)
Background & Aims: Recent studies have demonstrated an important role for Th-17 lymphocytes and other cytokines in pathogenesis of multiple sclerosis. Although previous studies have demonstrated the anti-inflammatory potential of troxerutin, the effects of troxerutin on multiple sclerosis have not been studied so far. The present study was carried out to investigate the therapeutic effects of troxerutin on experimental autoimmune encephalomyelitis (EAE) by reducing the production of pro-inflammatory cytokines IL-17, IL-1, TNF-α, and reducing nitric oxide levels and reducing immune cell proliferation.
Materials & Methods: EAE was induced by MOG35-55 peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were placed in four therapeutic groups of 5. Treatment with troxerutin (135 mg/kg daily) was started in the treatment group when they developed a disability score. Signs of disease were recorded daily until the day 21 when mice were sacrificed. Then, Immune cells were tested to assess proliferation rate, cytokine, and nitric oxide by the 3-(4,5 dimethylthiozol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assay (ELISA), and Greiss, respectively.
Results: The troxerutin significantly decreased the clinical signs of established EAE. Troxerutin significantly decreased the production of pro-inflammatory cytokines IL-17, IL-1 TNF-α and decreased levels of nitric oxide, while reduced the proliferation of immune cells (p<0.05).
Conclusion: Parallel with decreasing proliferation of Immune cells and cytokine production, troxerutin ameliorated established EAE.
Materials & Methods: EAE was induced by MOG35-55 peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were placed in four therapeutic groups of 5. Treatment with troxerutin (135 mg/kg daily) was started in the treatment group when they developed a disability score. Signs of disease were recorded daily until the day 21 when mice were sacrificed. Then, Immune cells were tested to assess proliferation rate, cytokine, and nitric oxide by the 3-(4,5 dimethylthiozol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assay (ELISA), and Greiss, respectively.
Results: The troxerutin significantly decreased the clinical signs of established EAE. Troxerutin significantly decreased the production of pro-inflammatory cytokines IL-17, IL-1 TNF-α and decreased levels of nitric oxide, while reduced the proliferation of immune cells (p<0.05).
Conclusion: Parallel with decreasing proliferation of Immune cells and cytokine production, troxerutin ameliorated established EAE.
Keywords: Experimental autoimmune encephalomyelitis, pro-inflammatory cytokines, troxerutin, Immune cells
Type of Study: Research |
Subject:
ایمونولوژی
References
1. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372: 1502-17. [DOI:10.1016/S0140-6736(08)61620-7] [PMID]
2. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15(9):545-58. [DOI:10.1038/nri3871] [PMID]
3. Wu GF, Alvarez E. The Immunopathophysiology of Multiple Sclerosis. Neurol Clin 2011;29:257-78. [DOI:10.1016/j.ncl.2010.12.009] [PMID] [PMCID]
4. Zhang JM, An J. Cytokines, Inflammation, and Pain. Int Anesthesiol Clin 2007;45:27-37. [DOI:10.1097/AIA.0b013e318034194e] [PMID] [PMCID]
5. Trapp BD, Nave KA. Multiple Sclerosis: An Immune or Neurodegenerative Disorder? Annu Rev Neurosci 2008;31:247-69. [DOI:10.1146/annurev.neuro.30.051606.094313] [PMID]
6. Mao P, Reddy PH. Is Multiple Sclerosis a Mitochondrial Disease? Biochim Biophys Acta 2009;1802:66-79. [DOI:10.1016/j.bbadis.2009.07.002] [PMID] [PMCID]
7. Goverman J. Autoimmune T Cell Responses in the Central Nervous System. Nat Rev Immunol 2009;9:393-407. [DOI:10.1038/nri2550] [PMID] [PMCID]
8. Wujek JR, Bjartmar C, Richer E, Ransohoff RM, Yu M, Tuohy VK, et al. Axon Loss in the Spinal Cord Determines Permanent Neurological Disability in an Animal Model of Multiple Sclerosis. J Neuropathol Exp Neurol 2002;61:23-32. [DOI:10.1093/jnen/61.1.23] [PMID]
9. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of Multiple Sclerosis Lesions: Implications for the Pathogenesis of Demyelination. Ann Neurol 2000; 47:707-17.
https://doi.org/10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q [DOI:10.1002/1531-8249(200006)47:63.0.CO;2-Q] [PMID]
10. Hamann I, Zipp F, Infante-Duarte C. Therapeutic Targeting of Chemokine Signaling in Multiple Sclerosis. J Neurol Sci 2008;274:31-8. [DOI:10.1016/j.jns.2008.07.005] [PMID]
11. Imitola J, Chitnis T, Khoury SJ. Cytokines in Multiple Sclerosis: From Bench to Bedside. Pharmacol Ther 2005;106:163-77. [DOI:10.1016/j.pharmthera.2004.11.007] [PMID]
12. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-Producing Cd4+ Effector T Cells Develop Via a Lineage Distinct from the T Helper Type 1 and 2 Lineages. Nat Immunol 2005;6:1123-32. [DOI:10.1038/ni1254] [PMID]
13. Hofstetter HH, Ibrahim SM, Koczan D, Kruse N, Weishaupt A, Toyka KV, et al. Therapeutic Efficacy of Il-17 Neutralization in Murine Experimental Autoimmune Encephalomyelitis. Cell Immunol 2005;237:123-30. [DOI:10.1016/j.cellimm.2005.11.002] [PMID]
14. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. Il-23 Drives a Pathogenic T Cell Population That Induces Autoimmune Inflammation. J Exp Med 2005;201:233-40. [DOI:10.1084/jem.20041257] [PMID] [PMCID]
15. Kolls JK, Linden A. Interleukin-17 Family Members and Inflammation. Immunity 2004;21:467-76. [DOI:10.1016/j.immuni.2004.08.018] [PMID]
16. Begolka WS, Miller SD. Cytokines as Intrinsic and Exogenous Regulators of Pathogenesis in Experimental Autoimmune Encephalomyelitis. Res Immunol 1998;149:771-81. [DOI:10.1016/S0923-2494(99)80004-2] [PMID]
17. Pare A, Mailhot B, Levesque SA, Lacroix S. Involvement of the Il-1 System in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: Breaking the Vicious Cycle between Il-1beta and Gm-Csf. Brain Behav Immun 2017;62:1-8. [DOI:10.1016/j.bbi.2016.07.146] [PMID]
18. Martin D, Near SL. Protective Effect of the Interleukin-1 Receptor Antagonist (Il-1ra) on Experimental Allergic Encephalomyelitis in Rats. J Neuroimmunol 1995;6:241-5. [DOI:10.1016/0165-5728(95)00108-E] [PMID]
19. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The Encephalitogenicity of T(H)17 Cells Is Dependent on Il-1- and Il23-Induced Production of the Cytokine Gm-Csf. Nat Immunol 2011;12:568-75. [DOI:10.1038/ni.2031] [PMID] [PMCID]
20. Wang K, Song F, Fernandez-Escobar A, Luo G, Wang JH, Sun Y. The Properties of Cytokines in Multiple Sclerosis: Pros and Cons. Am J Med Sci 2018; 356(6):552-60. [DOI:10.1016/j.amjms.2018.08.018] [PMID]
21. Encinas JM, Manganas L, Enikolopov. Nitric Oxide and Multiple Sclerosis. Curr Neurol Neurosci Rep 2005; 5:232-8. [DOI:10.1007/s11910-005-0051-y] [PMID]
22. Smith KJ, Lassmann H. The role of nitric oxide in multiple sclerosis. Lancet Neurol 2002; 1(4):232-41. [DOI:10.1016/S1474-4422(02)00102-3] [PMID]
23. Lan M, Tang X, Zhang J, Yao Z. Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes. Rev Neurosci 2018; 29(1):39-53. [DOI:10.1515/revneuro-2017-0033] [PMID]
24. Luccarini I, Ballerini C, Biagioli T, Biamonte F, Bellucci A, Rosi MC, et al. Combined treatment with atorvastatin and minocycline suppresses severity of EAE. Exp Neurol 2008; 211(1): 214-26. [DOI:10.1016/j.expneurol.2008.01.022] [PMID]
25. Siegers CP, Syed Ali S, Tegtmeier M. Aescin and troxerutin as a successful combination for the treatment of inner ear perfusion disturbances. Phytomedicine 2008; 15(3): 160-3. [DOI:10.1016/j.phymed.2007.11.025] [PMID]
26. Vinothkumar R, Vinoth Kumar R, Karthikkumar V, Viswanathan P, Kabalimoorthy J, Nalini N. Oral supplementation with troxerutin (trihydroxyethylrutin), modulates lipid peroxidation and antioxidant status in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Environ Toxicol Pharmacol 2014; 37: 174-84. [DOI:10.1016/j.etap.2013.11.022] [PMID]
27. Lu J, Wu DM, Zheng ZH, Zheng YL, Hu B, Zhang ZF. Troxerutin protects against high cholesterol-induced cognitive deficits in mice. Brain 2011; 134: 783-97. [DOI:10.1093/brain/awq376] [PMID]
28. Liu CM, Ma JQ, Lou Y. Chronic administration of troxerutin protects mouse kidney against D-galactose-induced oxidative DNA damage. Food Chem Toxicol 2010; 48(10): 2809-17. [DOI:10.1016/j.fct.2010.07.011] [PMID]
29. Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD+-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice. Biochem Pharmacol 2014; 91(1): 74-86. [DOI:10.1016/j.bcp.2014.07.002] [PMID]
30. Lu J, Wu DM, Hu B, Cheng W, Zheng YL, Zhang ZF, et al. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system. Neurobiol Learn Mem 2010; 93(2): 157-64. [DOI:10.1016/j.nlm.2009.09.006] [PMID]
31. Badalzadeh R, Baradaran B, Alihemmati A, Yousefi B, Abbaszadeh A. Troxerutin Preconditioning and Ischemic Postconditioning Modulate Inflammatory Response after Myocardial Ischemia/Reperfusion Injury in Rat Model. Inflammation 2016;40(1):136-43. [DOI:10.1007/s10753-016-0462-8] [PMID]
32. Skundric DS, Zakarian V, Dai R, Lisak RP, Tse HY, James J. Distinct immune regulation of the response to H-2b restricted epitope of MOG causes relapsing-remitting EAE in H-2b/s mice. J Neuroimmunol 2003; 136(1-2): 34-45. [DOI:10.1016/S0165-5728(03)00005-5] [PMID]
33. van Meerloo J, Kaspers GJL, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol 2011; 731:237-45. [DOI:10.1007/978-1-61779-080-5_20] [PMID]
34. Griess P. Ber Deutsch Chem Ges 1879;12:426-8. [DOI:10.1002/cber.187901201117]
35. Jadidi-Niaragh F, Mirshafiey A. Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol 2011; 74(1): 1-13. [DOI:10.1111/j.1365-3083.2011.02536.x] [PMID]
36. Balasa R. T helper 17 cells in multiple scelerosis and experimental autoimmune encephalomyelitis. Rom J Neurol 2010; 9(4): 181-8. [Google Scholar]
37. Korn T, Oukka M, Kuchroo V, Bettelli E. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007; 19(6): 362-71. [DOI:10.1016/j.smim.2007.10.007] [PMID] [PMCID]
38. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, et al. Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple Sclerosis. Am J Pathol 2008;172:146-55. [DOI:10.2353/ajpath.2008.070690] [PMID] [PMCID]
39. Schofield C, Fischer SK, Townsend MJ, Mosesova S, Peng K, Setiadi AF, et al. Characterization of Il-17aa and Il-17ff in Rheumatoid Arthritis and Multiple Sclerosis. Bioanalysis 2016; 8:2317-27. [DOI:10.4155/bio-2016-0207] [PMID]
40. da Costa, DS, Hygino J, Ferreira TB, Kasahara TM, Barros PO, Monteiro C, et al. Vitamin D Modulates Different Il-17-Secreting T Cell Subsets in Multiple Sclerosis Patients. J Neuroimmunol 2016;299:8-18. [DOI:10.1016/j.jneuroim.2016.08.005] [PMID]
41. Bradley JR. Tnf-Mediated Inflammatory Disease. J Pathol 2008;214:149-60. [DOI:10.1002/path.2287] [PMID]
42. Cannella B, Raine CS. The Adhesion Molecule and Cytokine Profile of Multiple Sclerosis Lesions. Ann Neurol 1995;37:424-35. [DOI:10.1002/ana.410370404] [PMID]
43. Kuroda Y, Shimamoto Y. Human Tumor Necrosis Factor-Alpha Augments Experimental Allergic Encephalomyelitis in Rats. J Neuroimmunol 1991;34:159-64. [DOI:10.1016/0165-5728(91)90125-Q] [PMID]
44. Baker D, Butler D, Scallon BJ, O'Neill JK, Turk JL, Feldmann M. Control of Established Experimental Allergic Encephalomyelitis by Inhibition of Tumor Necrosis Factor (Tnf) Activity within the Central Nervous System Using Monoclonal Antibodies and Tnf Receptor-Immunoglobulin Fusion Proteins. Eur J Immunol 1994;24:2040-8. [DOI:10.1002/eji.1830240916] [PMID]
45. Kollias G, Douni E, Kassiotis G, Kontoyiannis D. The Function of Tumour Necrosis Factor and Receptors in Models of Multi-Organ Inflammation, Rheumatoid Arthritis, Multiple Sclerosis and Inflammatory Bowel Disease. Ann Rheum Dis 1999; 58:I32-39. [DOI:10.1136/ard.58.2008.i32] [PMID] [PMCID]
46. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous Inflammatory Demyelinating Disease in Transgenic Mice Showing Central Nervous System-Specific Expression of Tumor Necrosis Factor Alpha. Proc Natl Acad Sci U S A 1995;92:11294-8. [DOI:10.1073/pnas.92.24.11294] [PMID] [PMCID]
47. Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G, et al. Oligodendrocyte Apoptosis and Primary Demyelination Induced by Local Tnf/P55tnf Receptor Signaling in the Central Nervous System of Transgenic Mice: Models for Multiple Sclerosis with Primary Oligodendrogliopathy. Am J Pathol 1998;153:801-13. [DOI:10.1016/S0002-9440(10)65622-2] [PMID]
48. Bauer J, Berkenbosch F, Van Dam AM, Dijkstra CD. Demonstration of interleukin-1 beta in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level. J Neuroimmunol 1993; 48: 13 - 21. [DOI:10.1016/0165-5728(93)90053-2] [PMID]
49. Stroemer RP, Rothwell NJ. Cortical protection by localized striatal injection of IL-1ra following cerebral ischemia in the rat. J Cereb Blood Flow Metab 1997; 17: 597 - 604. [DOI:10.1097/00004647-199706000-00001] [PMID]
50. Yang GY, Liu XH, Kadoya C, Zhao YJ, Mao Y, Davidson BL, et al. Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist. J Cereb Blood Flow Metab 1998; 18; 840 - 7. [DOI:10.1097/00004647-199808000-00004] [PMID]
51. Downen M, Amaral TD, Hua LL, Zhao ML, Lee SC. Neuronal death in cytokine-activated primary human brain cell culture: role of tumor necrosis factor-alpha. Glia 1999; 28: 114 - 27.
https://doi.org/10.1002/(SICI)1098-1136(199911)28:2<114::AID-GLIA3>3.0.CO;2-O [DOI:10.1002/(SICI)1098-1136(199911)28:23.0.CO;2-O]
52. Stoll G, Jander S, Schroeter M. Cytokines in CNS disorders: neurotoxicity versus neuroprotection. J Neural Transm Suppl 2000; 59: 81 - 9. [DOI:10.1007/978-3-7091-6781-6_11] [PMID]
53. Lin RF, Lin TS, Tilton RG, Cross AH. Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study. J Exp Med 1993; 178: 643-8. [] [PMID] [PMCID]
54. Okuda Y, Nakatsuji Y, Fujimura H, Esumi H, Ogura T, Yanagihara T, et al. Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. J Neuroimmunol 1995; 62: 103-12. [DOI:10.1016/0165-5728(95)00114-H] [PMID]
55. Giovannoni G, Heales SJ, Land JM, Thompson EJ. The potential role of nitric oxide in multiple sclerosis. Am J Pathol 2008; 172(1):146-55. [Google Scholar]
56. Hooper DC, Ohnishi ST, Kean R, Numagami Y, Dietzschold B, Koprowski H. Local nitric oxide production in viral and autoimmune diseases of the central nervous system. Proc Natl Acad Sci USA 1995; 92: 5312-6. [DOI:10.1073/pnas.92.12.5312] [PMID] [PMCID]
57. Zhang Z, Wang X, Zheng G, Shan Q, Lu J, Fan S, et al. Troxerutin attenuates enhancement of hepatic gluconeogenesis by inhibiting NOD activation-mediated inflammation in highfat diet-treated mice. Int J Mol Sci 2016; 18: 31. [DOI:10.3390/ijms18010031] [PMID] [PMCID]
58. Fan SH, Zhang ZF, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin protects the mouse kidney from d-galactosecaused injury through anti-inflammation and anti-oxidation. Int Immunopharmacol 2009; 9: 91-6. [DOI:10.1016/j.intimp.2008.10.008] [PMID]
59. Hoseindoost M, Alipour MR, Farajdokht F, Diba R, Bayandor P, Mehri K, et al. Effects of troxerutin on inflammatory cytokines and BDNF levels in male offspring of high-fat diet fed rats. Avicenna J Phytomed 2019; 9(6):597-605. [PMID] [PMCID]
60. Zhanga ZF, Zhanga YG, Fanb SH, Zhuanga J, Zheng YL, Lu J, et al. Troxerutin protects against 2,2 ,4,4 -tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion. J Hazard Mater 2015; 283;98-109. [DOI:10.1016/j.jhazmat.2014.09.012] [PMID]
61. Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin protects the mouse liver against oxidative stress-mediated injury induced by D-galactose. J Agric Food Chem 2009; 57(17):7731-6. [DOI:10.1021/jf9012357] [PMID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
