Muhammed YAYLA, Harun ÜN, Damla BİNNETOĞLU

Floretin ve floridzin'in primer nöron hücrelerinde paklitaksel ile indüklenen nöron hasarındaki koruyucu etkileri

Amaç: Kemoterapide sıklıkla kullanılan paklitaksel, nötropeni ve periferik nöropati gibi bazı ciddi yan etkilerle nöron hasarına neden olur. Biz bu çalışmada, floretin ve floridzin’ in paklitaksel kaynaklı nöronal hasar üzerindeki nöroprotektif etkilerini araştırdık. Gereç ve Yöntem: Floretin ve floridzin’ in nöroprotektif etkileri primer nöron hücreleri üzerindeki etkileri, hücre canlılığı, total oksidan ve antioksidan kapasiteleri ve kaspaz-3, kaspaz-9 ve TNF-α ekspresyonu test edilerek değerlendirilmiştir. Bulgular: Paklitaksel uygulaması hücre ölümüne, toplam oksidan seviyelerinin önemli ölçüde artmasına ve kaspaz-3, kaspaz-9 ve TNF-α gibi apoptotik genlerin aktivasyonuna neden oldu. Mikromolar konsantrasyonlardaki floretin ve floridzin tedavileri, toplam antioksidan seviyelerini artırarak paklitaksel kaynaklı hücre ölümünü azalttı. Ayrıca bu iki flavonoid, kaspaz-3, kaspaz-9 ve TNF-α gen ekspresyonlarını azaltarak nöron hücrelerini apoptozdan korudu. Bu nedenle, bu moleküller oksidatif hasardan geri kazanımı indükleyebilir ve normal hücresel koşulları düzenleyebilir. Sonuç: Bu çalışma, floretin ve floridzin’ in nöron hücrelerini paklitaksel kaynaklı hücre hasarından koruyabilen, antioksidan kapasitesini aktif olarak arttıran, oksidan seviyelerini normalleştiren ve sonuç olarak hücre ölümünü önlemede umut verici nöroprotektif potansiyelini göstermektedir.

Neuroprotective effects of phloretin and phloridzin on paclitaxel-induced neuronal damage in primary neuron cells

Purpose: Paclitaxel, is one of the most commonly used chemotherapeutic, causes neuron damage with some serious side effects such as neutropenia and peripheral neuropathy. In current study, we used phloretin and phloridzin to investigate their neuroprotective effects on paclitaxel-induced neuronal damage. Materials and Methods: The neuroprotective effects of phloretin and phloridzin has been analyzed on cell culture of primary neuron cells and evaluated by testing cell viability, total oxidant and total antioxidant capacities and expression of caspase-3, caspase-9 and TNF-α. Paclitaxel administration caused cell death and significant increase of total oxidant levels and activation of apoptotic genes such as caspase-3, caspase-9 and TNF-α. Results: Phloretin and phloridzin treatments at micromolar concentrations reduced paclitaxel-induced cell death by increasing total antioxidant levels. Also these two flavonoids protect neuron cells from apoptosis by decreasing caspase-3, caspase-9 and TNF-α gene expression. For this reason, these molecules may recover the oxidative damage, and restore normal cellular conditions. Conclusion: This study shows the promising neuroprotective ability of the phloretin and phloridzin able to protect neuron cells from injury induced by paclitaxel, actively increasing antioxidant capacity, normalizing oxidant levels and consequently avoiding cell death.

Keywords:

Paclitaxel phloretin, phloridzin, primary neuron cell,

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