The Effect of Erythropoietin on Methotrexate-Induced Renal Damage in Rats: Biochemical and Histopathological Studies

Year 2015, , 98 - 106, 09.09.2015

Betül Kabakcı Ergül Kurutaş , Sevgi Bakariş Meltem Güngör

https://doi.org/10.17826/cutf.23047

Cited By: 2

Abstract

Purpose: Methotrexate (MTX), a folic acid antagonist, is widely used as a cytotoxic chemotherapeutic agent for several malignancies and various inflammatory diseases. However, the efficacy of this agent often is limited by severe side effects and toxic conditions. In our study, it was aimed to investigate the effect of erythropoietin (EPO) which is a potent antioxidant substance in oxidative damage induced-MTX. Material and Methods: Twenty-four female Sprague-Dawley sıçans were equally divided into three groups: Sham animals were administered subcutaneous injections of 0.2 mL of 0.9% NaCl, group MTX were administered subcutaneous injections of methotrexate (5 mg/kg), and MTX+EPO-treated animals were administered subcutaneous injections of methotrexate (5 mg/kg) and EPO (2000 IU/kg) once daily for 4 consecutive days. At the fifth day, the Araştırma Makalesi / Research Article 98 Cilt/Volume 40 Yıl/Year 2015 Metotreksat -Eritropoetinin animals were sacrified, and kidneys were excised. Catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney tissue homogenates were measured as spectrophotometric. Tissues were evaluated as histopathologic with ligh microscope. Results: MDA levels in the Sham and MTX+EPO groups were significantly lower than those in the MTX group of both tissues (p<0.05). CAT and SOD activities in the Sham and MTX+EPO groups were significantly higher than those in the MTX group (p<0.05). Both tissues damage was significantly less in the MTX+EPO group than that in the MTX (p<0.05). EPO treatment reduced these histological damages. Conclusion: These data indicate that EPO may be useful therapeutic use in preventing kidney injury in patients receiving chemotherapeutic agents

Keywords

Erythropoietin, methotrexate, liver, kidney, oxidative stress biomarkers

Metotreksat ile İndüklenmiş Sıçanlarda Böbrek Hasarı Üzerine Eritropoetinin Etkisi: Biyokimyasal ve Histopatolojik Çalışma

Abstract

Amaç: Metotreksat (MTX) çeşitli inflamatuvar hastalıklarda ve bazı kanserler de çok yaygın olarak kullanılan sitotoksik bir ajan olup folik asit antagonistidir. Etkili bir ilaç olmasına rağmen, sıklıkla yan etki ve toksik etkileri nedeni ile kullanımı kısıtlanmaktadır. Çalışmamızda, güçlü bir antioksidan madde olan Eritropoetin (EPO)’in MTX’e bağlı olarak oluşan oksidatif hasara karşı etkisinin araştırılması amaçlandı. Materyal ve Metod: Yirmi dört adet dişi Sprague-Dawley sıçan üç gruba ayrıldı. Gruplar; % 0,9’luk NaCI’den 0,2 mL subkutan enjeksiyon uygulanan Sham grubu; subkutan MTX (5mg/kg) enjeksiyonu uygulanan grup ve subkutan MTX (5mg/kg) ile EPO (2000 IU/kg) enjeksiyonu uygulanan grup olarak belirlendi. İşlem günde bir kez olmak üzere 4 gün boyunca uygulandı. Beşinci günde sıçanlar öldürüldü, böbrek dokuları çıkarıldı. Böbrek dokularında katalaz (CAT), süperoksit dismutaz (SOD) ve malondialdehit (MDA) düzeyleri spektrofotometrik olarak ölçüldü. Dokuların histopatolojik incelemesi ışık mikroskopisinde yapıldı. Bulgular: Böbrek dokusunda MDA düzeyleri, Sham grubu ve MTX+EPO grubunda, MTX grubuna göre önemli ölçüde düşük bulundu (p<0,05). Buna karşın, Sham grubu ve MTX+EPO grubunda CAT ve SOD aktiviteleri anlamlı derecede yüksek bulundu (p<0,05). MTX+EPO grubunda hem karaciğer hem de böbrek doku hasarının MTX grubu ile kıyaslandığında önemli ölçüde azaldığı gözlendi (p<0,05). Histopatolojik olarak sadece metotreksat verilen grupta belirgin tübül hasarı ve enflamasyon varken EPO uygulanan gruplarda bu hasarlar azalmıştı. Sonuç: Bu veriler, EPO’ nun kemoterapötik ilaçlara bağlı oluşan böbrek hasarına karşı koruyucu olarak kullanılabileceğini ortaya koymaktadır

Keywords

eritropoetin, metotreksat, karaciğer, böbrek, oksidatif stres biyobelirteçleri

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