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.

ISSN

1177-8881

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

85071183064

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Indexed in Scopus

yes

Open Access

yes

Open Access Type

Gold: This publication is openly available in an open access journal/series

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