Effect of N-acetylcysteine on cisplatin induced apoptosis in rat kidney

Yıl 2022, Cilt: 47 Sayı: 2, 519 - 525, 30.06.2022

Inayet Gunturk Gönül Şeyda Seydel Fatma Dağlı Arzu Yay Cevat Yazıcı Kader Köse

Öz

Purpose: Cisplatin is one of the most potent and widely used chemotherapeutic agents for the treatment of a wide variety of solid organ cancers. However, due to various side-effects such as nephrotoxicity, its therapeutic applications are limited. In the current study, it was aimed to investigate the effects of N-acetylcysteine (NAC), which is an effective antioxidant and anti-inflammatory agent, on cisplatin-induced apoptosis in rat kidneys.
Materials and Methods: Twentyfour male Wistar rats were separated into 4 equal groups: Control, NAC-250, cisplatin (CP), and CP+NAC groups. Rats in the experimental groups were treated with intraperitoneally (i.p.) single-dose cisplatin (10 mg/kg) and NAC (i.p., 250 mg/kg) for 3 days.
Results: At the end of the experiment, nephrotoxicity was confirmed by blood urea nitrogen and creatinine levels, and the apoptotic changes were demonstrated by TdT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3 levels in rat kidneys. The number of TUNEL-positive cells and caspase-3 levels were significantly increased by cisplatin. Treating the rats with NAC significantly decreased TUNEL-positive cells and caspase-3 levels.
Conclusion: These data suggest that apoptotic cell death is involved in the pathogenesis of cisplatin-induced nephrotoxicity, and that the inhibition of apoptosis plays a central role in the beneficial effects of NAC.

Anahtar Kelimeler

Cisplatin, N-acetylcysteine, Apoptosis

Proje Numarası

TDK-2014-5056

N-asetilsisteinin rat böbreklerinde sisplatin ile indüklenen apoptoz üzerine etkisi

Öz

için en güçlü ve yaygın olarak kullanılan kemoterapötik ajanlardan biridirAncak nefrotoksisite gibi çeşitli yan etkileri nedeniyle terapötik uygulamaları sınırlıdır. Bu çalışmada, etkili bir antioksidan ve antienflamatuar ajan olan N-asetilsistein (NAC)’in rat böbreklerinde sisplatin kaynaklı apoptoz üzerindeki etkilerinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: Wistar cinsi erkek ratlar eşit sayıda olacak şekilde 4 gruba ayrıldı: Kontrol, NAC-250, sisplatin (CP) ve CP+NAC. Gruplardaki ratlara tek doz sisplatin (10 mg/kg) ve 3 gün NAC (250 mg/kg) intraperitoneal (i.p.) olarak uygulandı.
Bulgular: Deneyin sonunda, nefrotoksisite, kan üre nitrojen ve kreatinin seviyeleri ile doğrulandı ve apoptotik değişiklikler, sıçan böbreklerinde TdT aracılı deoksiüridin trifosfat nick-end etiketleme (TUNEL) ve kaspaz-3 seviyeleri ile gösterildi. TUNEL pozitif hücre sayısı ve kaspaz-3 seviyeleri sisplatin ile önemli ölçüde arttı. Sıçanları NAC ile tedavi etmek, TUNEL pozitif hücreleri ve kaspaz-3 seviyelerini önemli ölçüde azalttı.
Sonuç: Bu veriler, apoptotik hücre ölümünün sisplatin ile indüklenen nefrotoksisitenin patogenezinde etkili olduğunu ve apoptoz inhibisyonunun NAC'ın faydalı etkilerinde merkezi bir rol oynadığını göstermektedir.

Anahtar Kelimeler

Sisplatin, N-asetilsistein, Apoptoz

Destekleyen Kurum

Erciyes Üniversitesi

Proje Numarası

TDK-2014-5056

Kaynakça

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