Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

Abstract

Objective: Methotrexate (MTX) is known to have deleterious side effects on lung tissue. We aimed to investigate the effects of erythropoietin (EPO) and N-acetyl-cysteine (NAC) on MTX-induced lung injury in rats. Study Design: Animal experiment. Material and Methods: Twenty-six female Sprague-Dawley rats were divided into 4 groups. Sham group, 0.3 mL saline; MTX group, 5 mg/kg MTX; EPO group, 5mg/kg MTX and 2000 IU/kg EPO; NAC group, 5 mg/kg MTX and 200 mg/kg NAC were administered once daily for 4 consecutive days. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and inflammation and congestion scores in lung tissues were evaluated. Results: In MTX group MDA were significantly higher, CAT and SOD were significantly lower than in sham, EPO and NAC groups (p<0.005). In EPO group MDA, CAT, and SOD were higher, but not significant than those in group NAC (p>0.005). In group MTX both scores were significantly higher than in sham (p<0.005). The congestion score of group MTX was significantly higher than those of group EPO and NAC (p<0.005). Conclusion: EPO and NAC have significant preventive effects on MTX-induced lung injury in rats. Decreased antioxidant capacity and increased MDA level may cause the oxidative damage in MTX group. Also, higher antioxidant capacity and lower MDA level may be a response to oxidative stress in EPO and NAC groups. Turkish Başlık: Eritropoietin ve N-Asetilsistein'in Ratlarda, Metotreksat ile Oluşturulan Akciğer Hasarı Üzerine Koruyucu Etkisi Anahtar Kelimeler: Metotreksat, akciğer, oksidatif hasar, eritropoetin, N-asetil-sistein Amaç: Metotreksat (MTX)'ın akciğer dokusu üzerine zararlı etkileri olduğu bilinmektedir. Biz sıçanlarda MTX ile oluşturulan akciğer hasarı üzerine, eritropoietin (EPO) ve N-asetil-sistein (NAC)' in etkilerini araştırmayı amaçladık. Gereç ve Yöntemler: Yirmi altı dişi Sprague-Dawley sıçan 4 gruba ayrıldı. Sham grubuna, 0.3 ml serum fizyolojik; MTX grubuna, 5 mg/kg MTX; EPO grubuna, 5mg/kg MTX ve 2000 IU/kg EPO; NAC grubuna, 5 mg/kg MTX ile 200 mg/kg NAC 4 gün boyunca hergün, günde bir kez uygulandı. Malondialdehit (MDA), süperoksit dismutaz (SOD), katalaz (CAT) ve akciğer dokusunda inflamasyon ve konjesyon skorları değerlendirildi. Bulgular: MTX grubunda sham, EPO ve NAC gruplarındakine göre MDA anlamlı olarak yüksek, CAT ve SOD ise anlamlı olarak düşük idi. MDA, CAT ve SOD EPO grubunda, NAC grubundakine göre anlamlı olmayarak yüksek idi. Her iki skor MTX grubunda, sham grubundakine göre anlamlı olarak yüksek bulunmuştur. Konjesyon skoru MTX grubunda EPO ve NAC gruplarındakine göre anlamlı olarak yüksek saptandı. Sonuç: EPO ve NAC sıçanlarda MTX ile oluşturulan akciğer hasarı üzerine önemli koruyucu etkileri var. MTX grubunda azalmış antioksidan kapasite ve yüksek MDA düzeyi oksidatif hasara neden olmuş olabilir. Ayrıca, EPO ve NAC gruplarında yüksek antioksidan kapasite ve düşük MDA düzeyi oksidatif strese karşı oluşan bir yanıt olabilir.

Keywords

• Methotrexate, lung, oxidative damage, erythropoietin, N-acetyl-cysteine

Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

Öz

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