Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition

dc.authorid0000-0002-8284-8317
dc.authorscopusid8529768100
dc.authorscopusid49763173800
dc.authorscopusid57222464081
dc.authorscopusid57223639849
dc.authorscopusid55367802000
dc.authorscopusid54973672700
dc.authorscopusid55607621300
dc.contributor.authorKeskin, Halil
dc.contributor.authorKeskin, Filiz
dc.contributor.authorTavaci, Taha
dc.contributor.authorHalıcı, Hamza
dc.contributor.authorYüksel, Tuğba Nurcan
dc.contributor.authorÖzkaraca, Mustafa
dc.contributor.authorHalıcı, Zekai
dc.date.accessioned2022-05-11T14:41:12Z
dc.date.available2022-05-11T14:41:12Z
dc.date.issued2021
dc.departmentFakülteler, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.description.abstractThis study aims to investigate the protective effect of roflumilast, a phosphodiesterase (PDE)-4 enzyme inhibitor, and demonstrate its possible role in the development prevention of cerebral ischemia/reperfusion injury (CI/RI) after stroke induced by carotid artery ligation in juvenile rats. The rats were randomly divided into five groups: healthy group without any treatment, healthy group administered with 1 mg/kg roflumilast, CI group not administered with roflumilast, CI group administered with 0.5 mg/kg roflumilast, and CI group administered with 1 mg/kg roflumilast. In the CI groups, reperfusion was achieved 2h after ischemia induction; in the roflumilast groups, this drug was intraperitoneally administered immediately after reperfusion and at the 12(th) hour. At the end of 24h, the rats were sacrificed and their brain tissues removed for examination. The mRNA expressions obtained with real-time PCR of IL-1 beta, TNF-alpha, and NLRP3 significantly increased in the CI/RI-induced groups compared with the control group, and this increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Moreover, ELISA revealed that both IL-1 beta and IL-6 brain levels were significantly higher in the CI/RI-induced groups than in the controls. This increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Histopathological studies revealed that the values closest to those of the healthy group were obtained from the roflumilast groups. Nissl staining revealed that the Nissl bodies manifested normal density in the healthy and roflumilast-administered healthy groups, but were rare in the CI/RI-induced groups. Roflumilast treatment increased these decreased Nissl bodies with increasing doses. Observations indicated that the Nissl body density was close to the value in the healthy group in the CI/RI-induced group administered with 1 mg/kg roflumilast. Overall, roflumilast reduced cellular damage caused by CI/RI in juvenile rats, and this effect may be mediated by NLRP3.
dc.identifier.doi10.1111/1440-1681.13493
dc.identifier.endpage1110
dc.identifier.issn0305-1870
dc.identifier.issn1440-1681
dc.identifier.issue8en_US
dc.identifier.pmid33686709
dc.identifier.scopus2-s2.0-85105924925
dc.identifier.scopusqualityQ2
dc.identifier.startpage1103
dc.identifier.urihttps://doi.org/10.1111/1440-1681.13493
dc.identifier.urihttps://hdl.handle.net/20.500.11776/9105
dc.identifier.volume48
dc.identifier.wosWOS:000648739300001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorYüksel, Tuğba Nurcan
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofClinical and Experimental Pharmacology and Physiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectcerebral ischaemia
dc.subjectreperfusion injury
dc.subjectIL&#8208
dc.subject1&#946
dc.subjectIL&#8208
dc.subject6
dc.subjectjuvenile rat
dc.subjectNLRP3
dc.subjectroflumilast
dc.subjectstroke
dc.subjectTNF&#8208
dc.subject&#945
dc.subjectIschemic-Stroke
dc.subjectRisk-Factors
dc.subjectPhosphodiesterase-4 Inhibitor
dc.subjectReperfusion Injury
dc.subjectRolipram
dc.subjectSildenafil
dc.subjectMechanisms
dc.subjectChildren
dc.subjectTherapy
dc.subjectTargets
dc.titleNeuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition
dc.typeArticle

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