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2022-02-27Zeitschriftenartikel DOI: 10.18452/24720
Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study
dc.contributor.authorMohamed, Doaa I.
dc.contributor.authorAlaa El-Din Aly El-Waseef, Dalia
dc.contributor.authorNabih, Enas
dc.contributor.authorEl-Kharashi, Omnyah A.
dc.contributor.authorAbd El-Kareem, Hanaa F.
dc.contributor.authorAbo Nahas, Hebatallah H.
dc.contributor.authorA. Abdel-Wahab, Basel
dc.contributor.authorHelmy, Yosra A.
dc.contributor.authorAlshawwa, Samar
dc.contributor.authorM. Saied, Essa
dc.date.accessioned2022-06-02T14:53:39Z
dc.date.available2022-06-02T14:53:39Z
dc.date.issued2022-02-27none
dc.date.updated2022-03-23T04:53:09Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/25380
dc.description.abstractAlcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectalcoholismeng
dc.subjectstatinseng
dc.subjectatorvastatineng
dc.subjectacetylsalicylic acideng
dc.subjecthistopathologyeng
dc.subjectmiRNA155eng
dc.subjectNLRP3 inflammasomeseng
dc.subjectmolecular dockingeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleAcetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Studynone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/25380-0
dc.identifier.doihttp://dx.doi.org/10.18452/24720
dc.type.versionpublishedVersionnone
local.edoc.pages26none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn1999-4923
dcterms.bibliographicCitation.doi10.3390/pharmaceutics14030529none
dcterms.bibliographicCitation.journaltitlePharmaceuticsnone
dcterms.bibliographicCitation.volume14none
dcterms.bibliographicCitation.issue3none
dcterms.bibliographicCitation.articlenumber529none
dcterms.bibliographicCitation.originalpublishernameMDPInone
dcterms.bibliographicCitation.originalpublisherplaceBaselnone
bua.departmentMathematisch-Naturwissenschaftliche Fakultätnone

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