Ratlarda Siklofosfamid ile İndüklenen Hepatotoksisite Üzerine Kuersetinin Etkileri

Yıl 2019, Cilt: 46 Sayı: 1, 41 - 50, 03.03.2019

Semin Gedikli , Emin Şengül

https://doi.org/10.5798/dicletip.534825

Cited By: 3

Öz

Amaç: Siklofosfamid (CYP), karaciğer ve akciğer gibi birçok
organda toksisiteye neden olur. Pek çok çalışmada bazı antioksidanların CYP'nin
yan etkilerine karşı koruyucu etkileri olduğu gösterilmiştir. Bu çalışmada,
kuersetinin histolojik ve biyokimyasal yöntemler kullanılarak sıçanlarda CYP
ile indüklenen hepatotoksisite üzerindeki koruyucu etkisinin araştırılması
amaçlanmıştır.

Yöntemler: Otuz Sprague-Dawley erkek sıçan 5 gruba ayrıldı.
Kontrol grubuna 7 gün boyunca intragastrik olarak mısıryağı verildi. CYP
grubuna 7 gün intragastrik olarak mısır yağı verildi ve 7. günde
intraperitoneal olarak CYP (200 mg/kg) uygulandı. 7 gün boyunca Q50+CYP ve
Q100+CYP gruplarına sırasıyla kuersetin verildi ve 7. günde tek doz CYP (200
mg/kg) uygulandı. Q100 grubuna günde 100 mg/kg dozda kuersetin verildi. 8.
günde biyokimyasal ve histopatolojik incelemeler için kan örnekleri ve
karaciğer dokuları alındı.

Bulgular: MDA seviyesinin kontrol grubu ile
karşılaştırıldığında CYP grubunda belirgin olarak yüksek olduğunu ve kuersetin
uygulaması ile azaldığını tespit ettik. SOD ve GSH düzeyleri CYP grubunda
kontrol, Q50+CYP, Q100+CYP ve Q100 gruplarına göre azalmıştı. Histolojik
analizlerde CYP grubunda sinüsoidal dilatasyon, mononükleer hücre infiltrasyonu
ve vasküler konjesyon gözlenirken, bu dejeneratif değişikliklerin kuersetin
uygulaması ile azaldığı tespit edildi. TUNEL yönteminde, CYP grubunda kontrol
grubuna kıyasla fazla sayıda TUNEL pozitif hepatosit tespit edildi. Ayrıca Bax
ve Caspase-3 immunpozitivitesi açısından CYP grubunda diğer gruplara oranla
imünpozitiflik fazla iken, Bcl-2 immunpozitivitesi CYP grubunda diğer
gruplardan daha düşüktü.

Sonuç: Elde ettiğimiz sonuçlar, kuersetinin siklofosfamidle
indüklenen hepatotoksisite üzerinde koruyucu etkiye sahip olduğunu
göstermektedir.

Anahtar Kelimeler

Siklofosfamid, Kuersetin, Karaciğer

Kaynakça

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