Drug design, development and therapy, 2019-08, Vol.13, p.2715-2727
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach
- Ist Teil von
- Drug design, development and therapy, 2019-08, Vol.13, p.2715-2727
- Ort / Verlag
- New Zealand: Dove Medical Press Limited
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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 -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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1177-8881eISSN: 1177-8881DOI: 10.2147/DDDT.S207310Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1cf78bd1e7124796b5e7ac5f17afd41d
- Format
- –
- Schlagworte
- Alcoholism, Analysis, Animals, Anti-inflammatory agents, Antioxidants, Antioxidants (Nutrients), Apoptosis, Biochemistry, Brain, Brain research, Caspase, Caspase-3, Celecoxib, Celecoxib - administration & dosage, Celecoxib - chemistry, Celecoxib - pharmacology, Computational Biology, Computational neuroscience, Computer simulation, Cortex, Cytokines, Disease Models, Animal, Docking, Ethanol, Ethanol - administration & dosage, Ethanol - adverse effects, FDA approval, Glutathione, Glutathione transferase, Hippocampus, Homology, In vivo methods and tests, Inflammation, Injections, Intraperitoneal, Interleukin 1, Ligands, Male, Melatonin, Melatonin - administration & dosage, Melatonin - chemistry, Melatonin - pharmacology, Molecular Docking Simulation, Molecular dynamics, Neurodegeneration, Neurodegenerative Diseases - chemically induced, Neurodegenerative Diseases - prevention & control, Neurons, Neuroprotection, Neuroprotective Agents - administration & dosage, Neuroprotective Agents - chemistry, Neuroprotective Agents - pharmacology, Nitric oxide, Nitric-oxide synthase, Nitrogen oxides, Nonsteroidal anti-inflammatory agents, Original Research, Oxidative stress, Pharmaceutical sciences, Proteins, Rats, Rats, Sprague-Dawley, Simulation, Three dimensional models, TLR4 protein, Toll-like receptors, Tumor necrosis factor, Tumor necrosis factor-α