Document Type
Article
Source of Publication
Drug Design, Development and Therapy
Publication Date
1-1-2019
Abstract
© 2019 Al Kury et al. This work is published and licensed by Dove Medical Press Limited. 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 down-regulated 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.
DOI Link
ISSN
Publisher
Dove Medical Press Ltd.
Volume
13
First Page
2715
Last Page
2727
Disciplines
Chemistry | Computer Sciences | Life Sciences | Medicine and Health Sciences
Keywords
Cortex, Docking, Ethanol, Hippocampus, Neurodegeneration, Simulation
Scopus ID
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Al Kury, Lina T.; Zeb, Alam; Ul Abidin, Zain; Irshad, Nadeem; Malik, Imran; Alvi, Arooj Mohsin; Khalil, Atif Ali Khan; Ahmad, Sareer; Faheem, Muhammad; Khan, Arif Ullah; Shah, Fawad Ali; and Li, Shupeng, "Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: A computational and pharmacological approach" (2019). All Works. 2493.
https://zuscholars.zu.ac.ae/works/2493
Indexed in Scopus
yes
Open Access
yes
Open Access Type
Gold: This publication is openly available in an open access journal/series
Included in
Chemistry Commons, Computer Sciences Commons, Life Sciences Commons, Medicine and Health Sciences Commons