Effects of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist on inflammation and degeneration of the nucleus pulposus

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dc.authoridOzbek, hanefi/0000-0002-8084-7855
dc.authoridYILMAZ, Ibrahim/0000-0003-2003-6337
dc.authorwosidOzbek, hanefi/O-3472-2019
dc.contributor.authorYilmaz, I
dc.contributor.authorAkalan, H.
dc.contributor.authorSirin, D. Yasar
dc.contributor.authorKaraarslan, N.
dc.contributor.authorKaplan, N.
dc.contributor.authorOzbek, H.
dc.date.accessioned2023-03-22T19:47:26Z
dc.date.available2023-03-22T19:47:26Z
dc.date.issued2022
dc.departmentBelirleneceken_US
dc.description.abstractOBJECTIVE: The study aimed to examine the effects of two drugs, an acetylcholinesterase inhibitor (AChEI) and an N-methyl-D-aspartate receptor (NMDAR) antagonist, on degenerated annulus fibrosus (AF) and nucleus pulposus (NP) cells and the extracellular matrix (ECM) structure in vitro. PATIENTS AND METHODS: Tissue samples were obtained from patients with intervertebral disc herniation (four males and four females; classified as Pfirmann stage IV) and used to prepare cell cultures. Untreated cell culture samples served as the control group. Study group samples were treated with donepezil, memantine or a combination of the two drugs. Cell viability, toxicity and proliferation were evaluated in all groups. Western blotting was used to examine changes in protein expression of signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (ser727), hypoxia-inducible factor (HIF)-1 alpha (HIF-1 alpha) and nucleotide-binding oligomerisation domain (NOD) leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. The alpha significance value was < 0.05. RESULTS: Analysis of the microscopy and commercial kit results revealed that cell proliferation was suppressed. and no cell death was observed. The protein expression levels of NLRP3, STAT3, ser727 and HIF-1 alpha were lower in the samples treated with donepezil and memantine at 72 h (p < 0.05). The protein expression levels of NLRP3, STAT3, ser727 and HIF-1 alpha were higher in the samples treated with the combination of donepezil and memantine (p < 0.05). CONCLUSIONS: The combined administration of memantine a NMDAR antagonist which can prevent neurodegeneration and donepezil an AChEI used for pain relief increased the protein expression levels in the anabolic pathway. However, it did not reduce the protein expression levels in the catabolic pathway. Therefore, further studies are needed to provide extensive insight into whether it may be among the potential targets for the therapy of intervertebral disc (IVD) diseases.en_US
dc.identifier.endpage4419en_US
dc.identifier.issn1128-3602
dc.identifier.issue12en_US
dc.identifier.pmid35776042en_US
dc.identifier.scopus2-s2.0-85133541368en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage4409en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14034/699
dc.identifier.volume26en_US
dc.identifier.wosWOS:000823313800001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherVerduci Publisheren_US
dc.relation.journalEuropean Review For Medical And Pharmacological Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectDonepezilen_US
dc.subjectHIF-1 alphaen_US
dc.subjectMemantineen_US
dc.subjectNLRP3en_US
dc.subjectser727en_US
dc.subjectSTAT3en_US
dc.subjectIntervertebral Disc Degenerationen_US
dc.subjectNlrp3 Inflammasomeen_US
dc.subjectHippocampal Tissueen_US
dc.subjectCellsen_US
dc.subjectPathwayen_US
dc.subjectActivationen_US
dc.subjectMemantineen_US
dc.subjectApoptosisen_US
dc.subjectDonepezilen_US
dc.subjectProtectsen_US
dc.titleEffects of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist on inflammation and degeneration of the nucleus pulposusen_US
dc.typeArticleen_US

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