Volume 22, Issue 3 (8-2019)
J Arak Uni Med Sci 2019, 22(3): 95-106 |
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:
Sanadgol N, Sharifzadeh M, Maleki P. Evaluation of Effects of Benzoaric Acid on the I-KB/NF-Kb Complex and Expression of Caspase-8 and -9 in Animal Model of Multiple Sclerosis. J Arak Uni Med Sci 2019; 22 (3) :95-106
URL: http://jams.arakmu.ac.ir/article-1-6028-en.html
URL: http://jams.arakmu.ac.ir/article-1-6028-en.html
1- Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran. Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran. , n.sanadgol@uoz.ac.ir
2- Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran.
3- Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
2- Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran.
3- Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
Abstract: (2588 Views)
Background and Aim: Regarding the importance of new treatments to control and treat multiple sclerosis (MS), in this study we investigated the role of Benzoaric acid (BA) on the neuro-inflammation and apoptosis processes in the cuprizone (cup)-induced animal model of MS.
Materials and Methods: In this experimental study, 35 males C57BL/6 mice were divided into five groups. The study groups were included, control: received six weeks of normal powdered food beside intraperitoneal (i.p.) injection of BA solvent (100 µL per day PBS) for the last two weeks, cup: received six weeks of powdered food contains 0.2% cup beside i.p. injection of BA solvent for the last two weeks and cup-treatment: received six weeks of powdered food contains 0.2% cup beside i.p. injection of 20, 40 and 80 mg/kg BA for the last two weeks. Eventually, the medial corpus callosum area of the animal’s brain was evaluated via western blot and Real-Time PCR methods.
Ethical Considerations: Ethical points were observed according to the declaration of Helsinki and relevant code of ethics, regarding minimizing harms during animal experimentation (UOZ-GR-9517-13).
Findings: Molecular studies have shown that BA-80 decreased mRNA (p <0.01) and protein expression of NF-KB and consequently increased I-KB/NF-KB ratio (p <0.05) and decreased inflammation in compare to cup group. Moreover, BA-80 decreased caspase-9 mRNA (p<0.01) and caspase-8 mRNA (p <0.05) and subsequently increased caspase-8/caspase-9 ratio (p<0.01) and decreased apoptosis in compare to cup group.
Conclusion: The dose of 80 mg/ml BA via decreasing cup-induced neuro-inflammation and neuro-apoptosis has protective effects in this model.
Materials and Methods: In this experimental study, 35 males C57BL/6 mice were divided into five groups. The study groups were included, control: received six weeks of normal powdered food beside intraperitoneal (i.p.) injection of BA solvent (100 µL per day PBS) for the last two weeks, cup: received six weeks of powdered food contains 0.2% cup beside i.p. injection of BA solvent for the last two weeks and cup-treatment: received six weeks of powdered food contains 0.2% cup beside i.p. injection of 20, 40 and 80 mg/kg BA for the last two weeks. Eventually, the medial corpus callosum area of the animal’s brain was evaluated via western blot and Real-Time PCR methods.
Ethical Considerations: Ethical points were observed according to the declaration of Helsinki and relevant code of ethics, regarding minimizing harms during animal experimentation (UOZ-GR-9517-13).
Findings: Molecular studies have shown that BA-80 decreased mRNA (p <0.01) and protein expression of NF-KB and consequently increased I-KB/NF-KB ratio (p <0.05) and decreased inflammation in compare to cup group. Moreover, BA-80 decreased caspase-9 mRNA (p<0.01) and caspase-8 mRNA (p <0.05) and subsequently increased caspase-8/caspase-9 ratio (p<0.01) and decreased apoptosis in compare to cup group.
Conclusion: The dose of 80 mg/ml BA via decreasing cup-induced neuro-inflammation and neuro-apoptosis has protective effects in this model.
Type of Study: Original Atricle |
Subject:
Basic Sciences
Received: 2019/02/19 | Accepted: 2019/06/19
Received: 2019/02/19 | Accepted: 2019/06/19
References
1. Cudrici C, Niculescu T, Niculescu F, Shin ML, et al. Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement. J Rehabil Res Dev. 2006; 43(1): 123-32.
2. Loren A, Rolak MD. Multiple Sclerosis: It's Not The Disease You Thought It Was. Clin Med Res. 2003; 1(1): 57-60.
3. Sanchooli J, Ramroodi N, Sanadgol N, Sarabandi V, Ravan H, Saebi-Rad R. Relationship between metalloproteinase 2 and 9 concentrations and soluble CD154 expression in Iranian patients with multiple sclerosis. The Kaohsiung journal of medical sciences. 2014; 30 (5), 235-242.
4. Azami M, YektaKooshali MH, Shohani M, Khorshidi A, Mahmudi L. Correction: Epidemiology of multiple sclerosis in Iran: A systematic review and meta-analysis. PLOS ONE. 2019; 14(7): e0219466.
5. McQualter JL, Bernard CC. Multiple sclerosis: a battle between destruction and repair. J Neurochem. 2007; 100(2): 295-306.
6. Joannides AJ, Chandran S. Human embryonic stem cells: an experimental and therapeutic resource for neurological disease. J Neurol Sci. 2008; 265(1-2): 84-8.
7. Franklin RJ. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci. 2002; 3(9): 705-14.
8. Battista D, Rutishauser U. Removal of polysialic acid triggers dispersion of subventricularly derived neuroblasts into surrounding CNS tissues. J Neurosci. 2010; 30(11): 3995-4003.
9. Karaky M, Fedetz M, Potenciano V, Andrés-León E, Codina AE, Barrionuevo C, Alcina A, Matesanz F. SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-κB inhibition. Hum Mol Genet. 2018; 27(23):4012-4023.
10. Stone S, Jamison S, Yue Y, Durose W, Schmidt-Ullrich R, Lin W. NF-κB Activation Protects Oligodendrocytes against Inflammation. J Neurosci. 2017; 37(38): 9332-9344.
11. Poorebrahim M, Asghari M, Abazari MF, Askari H, Sadeghi S, Taheri-Kafrani A, Nasr-Esfahani MH, Ghoraeian P, Aleagha MN, Arab SS, Kennedy D, Montaseri A, Mehranfar M, Sanadgol N. Immunomodulatory effects of a rationally designed peptide mimetic of human IFNβ in EAE model of multiple sclerosis. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 82: 49-61.
12. Ramroodi N, Khani M, Ganjali Z, Javan MR, Sanadgol N, Khalseh R, Ravan H, Sanadgol E, Abdollahi M. Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis. Immunol Invest. 2015; 44(7):694-712.
13. Sanadgol N, Maleki P. Study of the Effects of Ellagic Acid on Population and Activity of Central Nervous System Neuroglia Cells in the Cuprizone-induced Multiple Sclerosis. J Arak Uni Med Sci. 2018; 21 (6):34-46
14. Lockshin RA, Zakeri Z. Apoptosis, autophagy, and more. Int J Biochem Cell Biol. 2004; 36: 2405-19.
15. Crawford ED, Wells JA. Caspase substrates and cellular remodeling. Annu. Rev. Biochem. 2011; 80: 1055-1087.
16. Kreutzberg G W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312–318.
17. Barres BA, Hart IK, Coles HS, Burne JF, et al. Cell death and control of cell survival in the oligodendrocyte lineage. Cell. 1992; 70: 31-46.
18. Skripuletz T, Gudi V, Hackstette D, Stangel M. De-and remyelination in the CNS white and grey matter induced by cuprizone: the old, the new, and the unexpected. Histology and histopathology. 2011; 26(12): 1585-97.
19. Derosa G, Maffioli P, Sahebkar A. Ellagic Acid and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016; 928: 473-479.
20. Lepka K, Berndt C, Hartung HP, Aktas O. Redox Events as Modulators of Pathology and Therapy of Neuroinflammatory Diseases. Front Cell Dev Biol. 2016; 4: 63.
21. Sanadgol N, Golab F, Mostafaie A, et al. Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair. Toxicol Appl Pharmacol. 2018; 342: 86-98.
22. Sanadgol N, Golab F, Mostafaie A, Mehdizadeh M, et al. Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines. Cell Mol Biol (Noisy-le-grand). 2016; 62(12): 24-30.
23. Sanadgol N, Golab F, Askari H, Moradi F, et al. Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis. 2018; 33(1): 27-37.
24. Sanadgol N, Zahedani SS, Sharifzadeh M, Khalseh R, et al. Recent Updates in Imperative Natural Compounds for Healthy Brain and Nerve Function: A Systematic Review of Implications for Multiple Sclerosis. Curr Drug Targets. 2017; 18(13): 1499-1517.
25. Dalvi LT, Moreira DC, Andrade R Jr, Ginani J, et al. Ellagic acid inhibits iron-mediated free radical formation. Spectrochim Acta A Mol Biomol Spectrosc. 2016; 173: 910-917.
26. Sanadgol N, Golab F, Tashakkor Z, et al. Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis, Pharmaceutical Biology. 2017; 55: 1679-1687.
27. Umesalma S, Sudhandiran G. Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-κB, iNOS, COX-2, TNF-α, and IL-6 in 1, 2-dimethylhydrazine-induced rat colon. Clinical Pharmacology & Toxicology. 2010; 107: 650-655.
28. Skripuletz T, Hackstette D, Bauer K, Gudi V, et al. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain. 2013; 136: 147-67.
29. Mishra S, Vinayak M. Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway. Mol Biol Rep. 2013; 40(2): 1417-28.
30. El-Shitany NA, El-Bastawissy EA, El-Desoky K. Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of IL-10 via an antioxidant mechanism. Int Immunopharmacol. 2014; 19(2): 290-9.
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
