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Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach
PURPOSE: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological,...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683968/ https://www.ncbi.nlm.nih.gov/pubmed/31447548 http://dx.doi.org/10.2147/DDDT.S207310 |
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author | Al Kury, Lina T Zeb, Alam Abidin, Zain Ul Irshad, Nadeem Malik, Imran Alvi, Arooj Mohsin Khalil, Atif Ali Khan Ahmad, Sareer Faheem, Muhammad Khan, Arif-Ullah Shah, Fawad Ali Li, Shupeng |
author_facet | Al Kury, Lina T Zeb, Alam Abidin, Zain Ul Irshad, Nadeem Malik, Imran Alvi, Arooj Mohsin Khalil, Atif Ali Khan Ahmad, Sareer Faheem, Muhammad Khan, Arif-Ullah Shah, Fawad Ali Li, Shupeng |
author_sort | Al Kury, Lina T |
collection | PubMed |
description | PURPOSE: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. METHODS: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. RESULTS: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol. CONCLUSION: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers. |
format | Online Article Text |
id | pubmed-6683968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66839682019-08-23 Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach Al Kury, Lina T Zeb, Alam Abidin, Zain Ul Irshad, Nadeem Malik, Imran Alvi, Arooj Mohsin Khalil, Atif Ali Khan Ahmad, Sareer Faheem, Muhammad Khan, Arif-Ullah Shah, Fawad Ali Li, Shupeng Drug Des Devel Ther Original Research PURPOSE: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. METHODS: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. RESULTS: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol. CONCLUSION: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers. Dove 2019-08-02 /pmc/articles/PMC6683968/ /pubmed/31447548 http://dx.doi.org/10.2147/DDDT.S207310 Text en © 2019 Al Kury et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Al Kury, Lina T Zeb, Alam Abidin, Zain Ul Irshad, Nadeem Malik, Imran Alvi, Arooj Mohsin Khalil, Atif Ali Khan Ahmad, Sareer Faheem, Muhammad Khan, Arif-Ullah Shah, Fawad Ali Li, Shupeng Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title |
Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title_full |
Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title_fullStr |
Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title_full_unstemmed |
Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title_short |
Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
title_sort | neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683968/ https://www.ncbi.nlm.nih.gov/pubmed/31447548 http://dx.doi.org/10.2147/DDDT.S207310 |
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