The Ocular Endothelin System: A Novel Target for the Treatment of Endotoxin-Induced Uveitis With Bosentan

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dc.contributor.authorKeles, Sadullah
dc.contributor.authorHalici, Zekai
dc.contributor.authorAtmaca, Hasan Tarik
dc.contributor.authorYayla, Muhammed
dc.contributor.authorYildirim, Kenan
dc.contributor.authorEkinci, Metin
dc.contributor.authorBayraktutan, Zafer
dc.date.accessioned2020-06-25T18:12:12Z
dc.date.available2020-06-25T18:12:12Z
dc.date.issued2014
dc.departmentKırıkkale Üniversitesi
dc.descriptionYayla, Muhammed/0000-0002-0659-3084; ATMACA, HASAN TARIK/0000-0001-8379-4114
dc.description.abstractPURPOSE. We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS. Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 mu g) in Wistar rats. Rats were divided randomly into 10 groups (n=6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-alpha level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS. The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-alpha levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS. Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.en_US
dc.description.sponsorshipAtaturk University Scientific Experimental Project OfficeAtaturk University [2012/5]en_US
dc.description.sponsorshipSupported by Ataturk University Scientific Experimental Project Office to Project Number 2012/5.en_US
dc.identifier.citationclosedAccessen_US
dc.identifier.doi10.1167/iovs.14-14193
dc.identifier.endpage3524en_US
dc.identifier.issn0146-0404
dc.identifier.issn1552-5783
dc.identifier.issue6en_US
dc.identifier.pmid24833743
dc.identifier.scopus2-s2.0-84902245892
dc.identifier.scopusqualityQ1
dc.identifier.startpage3517en_US
dc.identifier.urihttps://doi.org/10.1167/iovs.14-14193
dc.identifier.urihttps://hdl.handle.net/20.500.12587/5796
dc.identifier.volume55en_US
dc.identifier.wosWOS:000339485800020
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAssoc Research Vision Ophthalmology Incen_US
dc.relation.ispartofInvestigative Ophthalmology & Visual Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectendotoxin-induced uveitisen_US
dc.subjectbosentanen_US
dc.subjectTNF-alphaen_US
dc.subjectiNOSen_US
dc.subjectendothelin-1en_US
dc.titleThe Ocular Endothelin System: A Novel Target for the Treatment of Endotoxin-Induced Uveitis With Bosentanen_US
dc.typeArticle

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