RENAL HÜCRELERDE METOTREKSAT KAYNAKLI SİTOTOKSİSİTE: KURKUMİN’İN KORUYUCU ROLÜ

Yıl 2020, , 281 - 292, 21.06.2020

Bilal Çiğ

https://doi.org/10.33715/inonusaglik.727031

Cited By: 1

Öz

Metotreksat (MET), akciğer, meme kanserleri ve lenfoma gibi çeşitli malignitelerin tedavisinde kullanılmaktadır. Bu neoplastik ajanın hepatorenal toksisite gibi çeşitli komplikasyonlara neden olması onun tedavide kullanımını sınırlamaktadır. Antiinflamatuvar etkileri çok iyi bilinen kurkumin (KUR)’in hepatorenal toksisite üzerindeki koruyucu etkileri literatürde ifade edilmiştir. Bu çalışmada metotreksat ile indüklenen oksidatif stres, proinflamatuar yanıtın kurkumin ile baskılanabileceğini varsaydık. Bu çalışma, metotreksat kaynaklı sitotoksisite ve oksidatif strese karşı kurkuminin koruyucu rolünü araştırmak için planlandı. Bu çalışmada metotreksat kaynaklı renal toksisite ve sonrasında gelişen moleküler olayları in-vitro araştırmak üzere fare böbrek kortikal toplama kanal hücreleri (mpkCCDc14) kullanıldı. Gruplar, Kontrol, KUR (10 μM ve 24 saat), MET (5 μM ve 24 saat) ve MET+KUR olarak dizayn edildi. Metotreksat kaynaklı oksidatif stres, mpkCCDc14 hücrelerinde mitokondriyal membran depolarizasyonu (MMD), sitozolik reaktif oksijen türleri (ROS) üretimi, apopitoz ve kaspaz-3, kaspaz-9 aktivasyon düzeyleri belirlenerek değerlendirildi. MET, oksidatif stresin hücre içinde artmasına neden olmasına rağmen, bu kurkumin tarafından azaltılmıştır. Kurkumin tedavisi, mitokondriyal disfonksiyonu düzenleyerek hücrelerde ROS oluşumunu bastırdı. Metotreksata maruz kalan hücrelerde apoptoz, kaspaz-3 ve kaspaz-9 aktiviteleri artmıştır. Bununla birlikte bu durum, kurkumin tedavisi ile modüle edildi. Sonuç olarak, metotreksat ile indüklenen oksidatif stres hücre hasarına ve proenflamatuar yanıta yol açarak kronik böbrek hastalığının ilerlemesinde mpkCCDc14 hücrelerinin rolünü güçlendirir. Kurkumin antioksidan, antienflamatuar ve anti-apopitotik etki ederek metotreksat kaynaklı sitozolik toksisiteye karşı yardımcı bir tedavi olabilir.

Anahtar Kelimeler

Apoptoz, Kurkumin, Metotreksat, Oksidatif stress

Methotrexate-Induced Cytotoxicity in Renal Cells: The Protective Role of Curcumin

Öz

Methotrexate (MET) is used in the treatment of various malignancies such as lung, breast cancers and lymphoma. The fact that it causes various complications such as hepatorenal toxicity limits its usage in treatment. The hepatorenal toxicity protective effects of Curcumin (CUR), whose anti-inflammatory effects are well known, have been expressed in the literature. In this study, we assumed that methotrexate-induced oxidative stress and proinflammatory response can be suppressed with curcumin treatment. This study was planned to investigate the protective role of curcumin against methotrexate-induced cytotoxicity and oxidative stress. In this study, mouse kidney cortical collection duct cells (mpkCCDc14) were used to investigate methotrexate-induced renal toxicity and subsequent molecular events in-vitro. The groups were designed as Control, CUR (10 μM and 24 hours), MET (5 μM and 24 hours) and MET+CUR. MET-induced oxidative stress was evaluated by determining mitochondrial membrane depolarization (MMD), cytosolic reactive oxygen species (ROS) production, apoptosis and caspase-3, caspase-9 activation levels in mpkCCDc14 cells. Although MET caused intracellular oxidative stress increase, this has been reduced by curcumin. Curcumin therapy regulated mitochondrial dysfunction and suppressed ROS formation in cells. Apoptosis, caspase-3 and caspase-9 activities have been increased in MET exposed cells. However, this condition was modulated by CUR therapy. As the result, MET-induced oxidative stress strengthens the role of mpkCCDc14 cells in the progression of chronic kidney disease, by leading to cell damage and creating a proinflammatory response. Curcumin can be an adjunctive therapy against methotrexate-induced cytosolic toxicity by antioxidant, anti-inflammatory and anti-apoptotic effects.

Anahtar Kelimeler

Apoptosis, Curcumin, Cytotoxicity, Methotrexate

Kaynakça

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