Volume 4, Issue 12 (Winter 2018)                   Caspian.J.Neurol.Sci 2018, 4(12): 30-34 | Back to browse issues page


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1- Neurosciences Research Center, Alzahra Institute, Isfahan University of Medical Sciences, Isfahan, Iran
2- PhD Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract:   (354 Views)
Background: Multiple Sclerosis (MS) is a demyelinating disorder of the Central Nervous System (CNS). In addition to the role of immune mediated mechanisms, oxidative and nitrosative stress also play an important role in neuropathology of MS. Bilirubin as an endogenous antioxidant has neuroprotective effects; however few studies have assessed the association between serum bilirubin level and MS.
Objectives: To evaluate serum level of bilirubin in MS patients.
Materials and Methods: Serum samples were collected from participants who referred to Kashani MS clinic in Isfahan between July 2016 and July 2017. A total of 80 MS patients (67 females and 13 males) and 94 Healthy Control subjects (HCs) (62 female and 32 male) enrolled. Compression of bilirubin levels between MS patients and HCs was done with covariance analysis. Regression analysis was used to assess the relation between bilirubin concentration and EDSS. SPSS software version 17.0 for Windows (SPSS, Chicago, IL, USA) was used.
Results: The level of Direct bilirubin (Dbil) was significantly lower in MS patients compared with HCs (P=0.02). Otherwise the serum concentration of Total bilirubin (Tbil) and in Direct bilirubin (Ibil) were higher in MS patients, but it was not statistically significant. There was a negative correlation between Extended Disability Status Scale (EDSS) and bilirubin levels (Tbil, Dbil and Ibil) but it was not significant. 
Conclusion: Bilirubin level is lower in MS patients and deficit of its antioxidant level may play role in neuropathology of MS.
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Type of Study: Research | Subject: Special
Received: 2017/11/30 | Accepted: 2017/12/19 | Published: 2018/01/1

References
1. Mahad D, Ziabreva I, Lassmann H, Turnbull D. Mitochondrial defects in acute multiple sclerosis lesions. Brain. 2008; 131(7):1722–35. doi: 10.1093/brain/awn105 [DOI:10.1093/brain/awn105]
2. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis The 2013 revisions. Neurology. 2014; 83(3):278-86. doi: 10.1212/WNL.0000000000000560 [DOI:10.1212/WNL.0000000000000560]
3. Perluigi M, Coccia R, Butterfield DA. 4-Hydroxy-2-nonenal, a reactive product of lipid peroxidation, and neurodegenerative diseases: A toxic combination illuminated by redox proteomics studies. Antioxid Redox Signal. 2012; 17(11):1590–609. doi: 10.1089/ars.2011.4406 [DOI:10.1089/ars.2011.4406]
4. Adibhatla RM, Hatcher JF. Lipid oxidation and peroxidation in CNS health and disease: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2010; 12(1):125–69. doi: 10.1089/ars.2009.2668 [DOI:10.1089/ars.2009.2668]
5. Lassmann H. Mechanisms of inflammation induced tissue injury in multiple sclerosis. J Neurol Sci. 2008; 274(1-2):45–7. doi: 10.1016/j.jns.2008.04.003 [DOI:10.1016/j.jns.2008.04.003]
6. Ljubisavljevic S, Stojanovic I, Vojinovic S, Milojkovic M, Dunjic O, Stojanov D, et al. Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks. Metab Brain Dis. 2013; 28(4):629–38. doi: 10.1007/s11011-013-9409-z [DOI:10.1007/s11011-013-9409-z]
7. Peng F, Yang Y, Liu J, Jiang Y, Zhu C, Deng X, et al. Low antioxidant status of serum uric acid, bilirubin and albumin in patients with neuromyelitis optica. Eur J Neurol. 2011; 19(2):277–83. doi: 10.1111/j.1468-1331.2011.03488.x [DOI:10.1111/j.1468-1331.2011.03488.x]
8. Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: The need for effective antioxidant therapy. J Neurol. 2004; 251(3):261–8. doi: 10.1007/s00415-004-0348-9 [DOI:10.1007/s00415-004-0348-9]
9. Fischer MT, Wimmer I, Höftberger R, Gerlach S, Haider L, Zrzavy T, et al. Disease-specific molecular events in cortical multiple sclerosis lesions. Brain. 2013; 136(6):1799–815. doi: 10.1093/brain/awt110 [DOI:10.1093/brain/awt110]
10. Acar A, Ugur Cevik M, Evliyaoglu O, Uzar E, Tamam Y, Arıkanoglu A, et al. Evaluation of serum oxidant/antioxidant balance in multiple sclerosis. Acta Neurol Belg. 2012; 112(3):275–80. doi: 10.1007/s13760-012-0059-4 [DOI:10.1007/s13760-012-0059-4]
11. Kapitulnik J. Bilirubin: An endogenous product of heme degradation with both cytotoxic and cytoprotective properties. Mol Pharmacol. 2004; 66(4):773–9. doi: 10.1124/mol.104.002832 [DOI:10.1124/mol.104.002832]
12. Choi AM, Alam J. Heme oxygenase-1: Function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol. 1996; 15(1):9–19. doi: 10.1165/ajrcmb.15.1.8679227 [DOI:10.1165/ajrcmb.15.1.8679227]
13. Chang EF, Wong RJ, Vreman HJ, Igarashi T, Galo E, Sharp FR, et al. Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. J Neurosci. 2003; 23(9):3689-96. PMID: 12736340 [DOI:10.1523/JNEUROSCI.23-09-03689.2003] [PMID]
14. Wang J, Zhuang H, Doré S. Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. Neurobiol Dis. 2006; 22(3):473–6. doi: 10.1016/j.nbd.2005.12.009 [DOI:10.1016/j.nbd.2005.12.009]
15. Liu Y, Zhu B, Wang X, Luo L, Li P, Paty DW, et al. Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis. J Neuroimmunol. 2003; 139(1-2):27–35. doi: 10.1016/s0165-5728(03)00132-2 [DOI:10.1016/S0165-5728(03)00132-2]
16. Liu Y, Li P, Lu J, Xiong W, Oger J, Tetzlaff W, et al. Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis. J Immunol. 2008; 181(3):1887–97. doi: 10.4049/jimmunol.181.3.1887 [DOI:10.4049/jimmunol.181.3.1887]
17. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2):292–302. doi: 10.1002/ana.22366 [DOI:10.1002/ana.22366]
18. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurol. 1983; 33(11):1444–52. doi: 10.1212/wnl.33.11.1444 [DOI:10.1212/WNL.33.11.1444]
19. Peng F, Deng X, Yu Y, Chen X, Shen L, Zhong X, et al. Serum bilirubin concentrations and multiple sclerosis. J Clin Neurosci. 2011; 18(10):1355–9. doi: 10.1016/j.jocn.2011.02.023 [DOI:10.1016/j.jocn.2011.02.023]
20. Deng J, Liang XM, Zhang XL, Ling SQ, Yang TT, Li M, Peng FH. Relationship between serum bilirubin levels and optic neuritis. Chin Med J. 2013; 126(17):3307-10. PMID: 24033954
21. Maher P, Schubert D. Signaling by reactive oxygen species in the nervous system. Cell Mol Life Sci. 2000; 57(8-9):1287–305. doi: 10.1007/pl00000766 [DOI:10.1007/PL00000766]
22. 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(7):988–97. doi: 10.1016/j.neuint.2013.02.025 [DOI:10.1016/j.neuint.2013.02.025]
23. Ryter SW, Alam J, Choi AMK. Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol Rev. 2006; 86(2):583–650. doi: 10.1152/physrev.00011.2005 [DOI:10.1152/physrev.00011.2005]
24. Emerson MR, LeVine SM. Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis. J Neurochem. 2008; 75(6):2555–62. doi: 10.1046/j.1471-4159.2000.0752555.x [DOI:10.1046/j.1471-4159.2000.0752555.x]
25. Ljubisavljevic S, Stojanovic I, Pavlovic R, Stojnev S, Stevanovic I, Sokolovic D, et al. The reduced glutathione and S-nitrosothiols levels in acute phase of experimental demyelination – Pathophysiological approach and possible clinical relevancy. Neuroscience. 2012; 219:175–82. doi: 10.1016/j.neuroscience.2012.05.062 [DOI:10.1016/j.neuroscience.2012.05.062]
26. Arriaga SM, Mottino AD, Almará AM. Inhibitory effect of bilirubin on complement-mediated hemolysis. Biochim Biophys Acta. 1999; 1473(2-3):329–36. doi: 10.1016/s0304-4165(99)00201-9 [DOI:10.1016/S0304-4165(99)00201-9]
27. Větvička V, Miler I, Šíma P, Táborský L, Fornůsbk L. The effect of bilirubin on the fc receptor expression and phagocytic activity of mouse peritoneal macrophages. Folia Microbiol. 1985; 30(4):373–80. doi: 10.1007/bf02927593 [DOI:10.1007/BF02927593]