Irmak FERAH OKKAY, Ufuk OKKAY, Yeşim YENİ, Özge BALPINAR, Ahmet HACIMÜFTÜOĞLU

Etanersept glutamat ile indüklenen nörotoksisiteye karşı nöronları korur: Bir in vitro çalışma

Mevcut çalışma, etanerseptin glutamat eksitotoksisitesinde koruyucu etkilerini, anti-inflamatuar ve anti-oksidan mekanizmalar yoluyla sıçan nöron kültüründe araştırmak için tasarlanmıştır. Sıçan kortikal nöronları glutamata maruz bırakıldı ve ardından etanerseptin glutamat toksisitesindeki etkisini değerlendirmek için etanersept çeşitli dozlarda (0.1, 0.5, 1, 10 μg/ml) uygulandı. Daha sonra nöronal hücre canlılığı, oksidatif stres ve inflamatuvar değişiklikleri inceledik. Etanerseptin, hücreleri glutamat eksitotoksisitesinden korudu. Hücre canlılığı analizlerimiz (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ve laktat dehidrogenaz), etanersept’in glutamat tarafından hasarlanan nöronların canlılık oranını belirgin şekilde arttırdığını ortaya koydu. Ayrıca, etanerseptin potansiyel antioksidan özellikleri MDA ve TOS gibi oksidatif stres parametrelerinin incelenmesi ve TAS ve SOD olarak ölçülen antioksidan parametreleri ile değerlendirildi. Ayrıca etanerseptin antiinflamatuar etkilerini değerlendirmek için TNF-α seviyeleri ölçüldü. Elde edilen veriler, etanercept’in inflamasyonu ve oksidatif parametreleri azaltırken antioksidatif parametrelerini arttırdığını kanıtladı. Bu çalışma, etanerseptin glutamat kaynaklı nöronal hücre ölümünü güçlü bir şekilde önlediğini göstermiştir. Bu çalışma, glutamat eksitotoksisitesine maruz kalan nöronlarda etanerseptin potansiyel koruyucu etkisini gösteren ilk çalışmadır ve etanerseptin terapötik potansiyeli hakkında yeni kapılar açmaktadır.

Anahtar Kelimeler:

Etanercept, glutamate, in vitro, neuroprotection, oxidative stress

Etanercept Protects Neurons Against Glutamate-Induced Neurotoxicity: An In Vitro Study

Current study was designed to investigate the protective effects of etanercept in glutamate excitotoxicity in rat neuronal culture through anti-inflammatory and anti-oxidant mechanisms. Rat cortical neurons were exposed to glutamate and to assess the effect of etanercept in glutamate toxicity, etanercept was applied at various doses (0.1, 0.5, 1, 10 μg/ml). Then we examined the changes in neuronal cell viability, oxidative stress and inflammation. Etanercept preserved cultured cells from glutamate excitotoxicity. Our cell viability analysis (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase) revealed that etanercept markedly increased the viability ratio of neurons injured by glutamate. In addition, the potential antioxidant property of etanercept was evaluated via the examination of oxidative stress parameters, such as MDA and TOS, and antioxidant parameters measured as TAS and SOD. Moreover, TNF-? levels were measured to evaluate anti-inflammatory effects of etanercept. Obtained data proved that etanercept increases the activity of the antioxidative parameters while decreased oxidative parameters and inflammation. The current study demonstrated that etanercept strongly prevents glutamate- induced neuronal cell death. This study is the first to demonstrate a potential protective effect of etanercept in neurons exposed to glutamate excitotoxicity and opens new doors on the therapeutic potential of etanercept.

Keywords:

Etanercept, glutamate, in vitro, neuroprotection, oxidative stress,

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