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" Effect of a number of selected NMDA receptor antagonists on experimental colitis and related mechanisms "
Ehsan Motaghi
Mohsen Minaiyan, Valiollah Hajhashemi, Parvin Mahzouni
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Isfahan University of Medical Science
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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111257
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| Doc. No
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T17840
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QU60,M917e,2017
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| Main Entry
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Motaghi , , Ehsan
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| Title & Author
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Effect of a number of selected NMDA receptor antagonists on experimental colitis and related mechanisms\ Ehsan Motaghi
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| College
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School of Pharmacy and Pharmaceutical Sciences
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| Date
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2017
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| Degree
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Ph.D
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| field of study
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Pharmacology
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154p.
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| Note
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Research Project No: 394789
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احسان متقی
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| Abstract
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Background: Ulcerative colitis treatment is not clearly established; therefore, new treatments are needed in this field. Anti-inflammatory effects of NMDA antagonists support the view that addition of the drugs with known anti-inflammatory properties to the pharmacological treatment of inflammatory bowel diseases (IBD) therapy may exerts positive effect in the course of the disease. The aim of this research was to examine the effects of three selected NMDA antagonists (memantine, dextromethorphan, dizocilpine (MK-801)) on trinitrobenzoic sulphunic acid (TNBS) induced ulcerative colitis in mice.The present study was also done to determine whether NMDA antagonists can alter the inflammatory processes and myeloperoxidase (MPO) activity, interleukine-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF-α)) levels enhancing during ulcerative colitis. Materials and methods: Male Swiss mice received the NMDA antagonists, memantine (12.5, 25, 50 mg/kg, i.p.), dextromethorphan (20, 60, 100 mg/kg, i.p.), dizocilpine (0.1, 1, 5 mg/kg, i.p.), and L-glutamic acid (2 g/kg, p.o.) (2) as a glutamate receptor agonist daily for 4 days started 24 h before and followed 3 days after colitis induction. Colitis was induced in mice by instillation of 0.1 mL of TNBS within the colon of mice. Dexamethasone (1 mg/kg, i.p.) was administered as reference drug. Four days after colitis induction, mice were euthanized and distal colons were evaluated macroscopically, histologically and biochemically. Biochemical assessments including MPO activity, IL-1β and IL-6 and TNF-α was performed.Results: Our results showed that memantine at both doses of 25 and 50 mg/kg attenuated weight loss (at least P<0.05), macroscopic colitis score (P<0.05, P<0.01, respectively), and pathologic changes (P<0.05, P<0.01, respectively), and decreased the level of MPO activity, TNF-α and interleukin 6 (P<0.01, P<0.001, respectively). However, interleukin 1β were reduced just at the dose of 50 mg/kg (P<0.05) and erosion area at all tested doses (P<0.001).Dizocilpine at all tested doses (0.1, 1 and 5 mg/kg) attenuated weight loss (at least P<0.05), and reduced the erosion area (P<0.01, P<0.001, P<0.001, respectively) and the level of TNF-α (P<0.001). This drug at the doses of 1 and 5 mg/kg also reduced macroscopic colitis score (P<0.01), colon weight (P<0.05), pathologic changes (P<0.01). However, the levels of MPO activity, and IL-1β were decreased at the dose of 1 mg/kg (P<0.05) while, IL-6 was reduced at 5 mg/kg (P<0.05). Dextromethorphan at all tested doses attenuated weight loss (at least P<0.05), macroscopic colitis score (P<0.05, P<0.01, P<0.01, respectively), erosion area (P<0.05, P<0.05, P<0.01, respectively) and TNF-α (P<0.05, P<0.05, P<0.01, respectively), IL-1β (P<0.05). Moreover, dextromethorphan at the doses of 60 and 100 mg/kg attenuated pathologic changes (P<0.05), and decreased the colon weight (P<0.05), and the levels of MPO activity (P<0.05, P<0.01, respectively), and interleukin 6 (P<0.05). L-glutamic acid (2 g/kg, p.o.) did not significantly alter the above-mentioned parameters and did not exacerbate the colitis. Discussion: The results of the current study showed the anti-inflammatory and anti-colitic properties of these NMDA antagonists in TNBS-induced colitis. So treatment of IBD by administering these NMDA antagonists have a beneficial effect in the healing process of the disease.
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| Descriptor
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NMDA
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Inflammatory bowel diseases
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Colitis
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Memantine
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Dextromethorphan
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Dizocilpine
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MK-801
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TNBS
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بیماری التهابی روده
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کولیت
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ممانتین
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دکسترومتورفان
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دیزوسیلپین
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Minaiyan , Mohsen
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Hajhashemi , Valiollah
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Mahzouni , Parvin
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Isfahan University of Medical Sciences
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| Translated Title Supplied by Cataloguer
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NMDA اثر منتخبی از آنتاگونیست های گیرنده بر روی کولیت آزمایشگاهی و مکانیسم های وابسته به آن
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