DAMLA BİNNETOĞLU, MUHAMMED YAYLA, TUĞBA NURCAN YÜKSEL

GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİNİN ETKİLERİ: İN VİTRO ÇALIŞMA

Amaç:Çalışmamızda eksitatör bir nörotransmitter olan glutamata bağlı nörotoksisitenin önlenmesi amacıyla güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin etkilerini araştırmayı amaçladık. Materyal ve Metot:Çalışmamızda yeni doğan sıçan korteksi kullanıldı. 10-5 M ve 2x10-5 M konsantrasyonlarında floretin ile 10- 5 M ve 2x10-5 M konsantrasyonlarında florizin ayrı ayrı uygulandıktan 2 saat sonra 3x10-3 M ve 6x10-3 M konsantrasyonlarında glutamat uygulaması gerçekleştirildi. Glutamat uygulamasından 6 saat sonra hücrelerden mRNA izolasyonu yapıldı. 24 saat sonra ise metiltiazol difenil tetrazolium (MTT) testi, total oksidan ve antioksidan kapasite ölçümleri gerçekleştirildi. Bulgular:Çalışmamızda glutamat artan dozlarda hücre canlılığını azaltırken floretin ve florizin uygulaması yüksek dozda en iyi nöroprotektif etkiyi ortaya koydu. Toksisiteye bağlı artan total oksidan düzey floretin ve florizin tarafından anlamlı derecede düzeltildi. Toksisite oluşturulan grupta azalan antioksidan kapasite floretin ve florizin uygulaması ile düzelme gösterdi. Floretin ve florizin tek başlarına uygulandığında hücre canlılığını anlamlı derecede etkilemezken, antioksidan kapasiteyi artırdı, oksidan düzeyi ise azalttı. Glutamat uygulaması sonrası artan tümör nekroz faktör-alfa (TNF-α) mRNA ekspresyonu, floretin ve florizin uygulaması ile anlamlı derecede azaldı. Glutamat uygulamasına bağlı artan kaspaz 9 ve kaspaz 3 mRNA ekspresyonu ise floretin ve florizin uygulaması ile anlamlı derecede düzelmegösterdi. Sonuç:Bu bulgular, güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin glutamata bağlı gelişen nörotoksisitede koruyucu olabileceğini ve glutamatın neden olduğu nörolojik bozuklukların önlenmesi için terapötik ajanlar olarak kullanılabileceğini gösterir.

Effects of Phloretin and Phlorizin on Glutamate-Induced Neuron Injury: in Vitro Study

Aim:In this study, we aimed to investigate the effects of phloretin and phlorizin which are potent antioxidants, anti inflammatory and antiapoptotic agents on the prevention of glutamate-induced neurotoxicity which is an excitatory neurotransmitter. Materials and Methods:In our study, the newly born rat cortex was used. Glutamate was applied in concentration 3x10-3 and 6x10-3 M 2 hours after application of phloretin in concentrations 10-5 M and 2x10-5 M and phlorizin in concentrations 10-5 and 2x10-5 M. mRNA isolation was performed from the cells 6 hours after glutamate administration. 24 hours later, metiltiazol difenil tetrazolium (MTT) test, total oxidant and antioxidant capacity measurements wereperformed. Results:In our study, phloretin and phlorizin showed the best neuroprotective effect in high dose, while glutamate reduced cell viability in increased doses. Increased total oxidant capacity due to toxicity has been significantly improved by phloretin and phlorizin. Decreased antioxidant capacity in the toxicity group showed improvement with the application of phloretin and phlorizin. When phloretin and phlorizin were applied alone, they did not affect cell viability significantly, they increased antioxidant capacity and decreased oxidant capacity. İncreased tumor necrosis factor-alpha (TNF-α) mRNA expression after glutamate administration decreased significantly with the application of phloretin and phlorizin. Increased caspase 9 and caspase 3 mRNA expression due to glutamate showed improvement with the application of phloretin andphlorizin. Conclusion:These ﬁndings suggest that phloretin and phlorizin, potent antioxidant, antiinflammatory and antiapoptotic agents, may be protective in glutamate-induced neurotoxicity and can be used as therapeutic agents for preventing glutamate-induced neurologicaldisorders.

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