Ratlarda Siklofosfamid ile İndüklenen Hepatotoksisite Üzerine Kuersetinin Etkileri
Amaç: Siklofosfamid (CYP), karaciğer ve akciğer gibi birçok organda toksisiteye neden olur. Pek çok çalışmada bazıantioksidanların CYP'nin yan etkilerine karşı koruyucu etkileri olduğu gösterilmiştir. Bu çalışmada, kuersetininhistolojik ve biyokimyasal yöntemler kullanılarak sıçanlarda CYP ile indüklenen hepatotoksisite üzerindeki koruyucuetkisinin araştırılması amaçlanmıştır.Yöntemler: Otuz Sprague-Dawley erkek sıçan 5 gruba ayrıldı. Kontrol grubuna 7 gün boyunca intragastrik olarakmısıryağı verildi. CYP grubuna 7 gün intragastrik olarak mısır yağı verildi ve 7. günde intraperitoneal olarak CYP (200mg/kg) uygulandı. 7 gün boyunca Q50+CYP ve Q100+CYP gruplarına sırasıyla kuersetin verildi ve 7. günde tek dozCYP (200 mg/kg) uygulandı. Q100 grubuna günde 100 mg/kg dozda kuersetin verildi. 8. günde biyokimyasal vehistopatolojik incelemeler için kan örnekleri ve karaciğer dokuları alındı.Bulgular: MDA seviyesinin kontrol grubu ile karşılaştırıldığında CYP grubunda belirgin olarak yüksek olduğunu vekuersetin uygulaması ile azaldığını tespit ettik. SOD ve GSH düzeyleri CYP grubunda kontrol, Q50+CYP, Q100+CYP veQ100 gruplarına göre azalmıştı. Histolojik analizlerde CYP grubunda sinüsoidal dilatasyon, mononükleer hücreinfiltrasyonu ve vasküler konjesyon gözlenirken, bu dejeneratif değişikliklerin kuersetin uygulaması ile azaldığı tespitedildi. 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 etkiyesahip olduğunu göstermektedir.
The Effects Of Quercetin On Cyclophosphamide Induced Hepatotoxicity In The Rats
Objective: Cyclophosphamide (CYP) causes toxicity in many organs, as liver and lung. Several studies have shown that some antioxidants have protective effects against CYP’ side effects. This study aimed to investigate the protective effect of quercetin-Q on CYP-induced hepatotoxicity in rats using histological and biochemical methods. Methods: Thirty Sprague-Dawley male rats were divided into 5 groups. Control group was given corn oil intragastrically for 7 days. CYP group was given intragastric corn oil for 7 days and CYP (200 mg/kg) was administered intraperitoneally on the 7th day. For 7 days, Q50+CYP and Q100+CYP groups were given quercetin and single dose CYP (200 mg/kg) was administered on the 7th day. Q100 group was given quercetin 100 mg/kg dose per day. On the 8th day, blood samples and liver tissues were taken for biochemical and histopathological examinations. Results: When MDA level was compared with the control group, it was higher in the CYP group and decreased with the administration of quercetin. SOD and GSH levels were lower in the CYP group compared to the other groups. Histological analysis revealed that sinusoidal dilatation and mononuclear cell infiltration were observed in the CYP group, and these degenerative changes were reduced by quercetin administration. In the TUNEL method, a large number of TUNEL positive hepatocytes were detected in the CYP group. Bcl-2 immunopositivities were lower in the CYP group, while Bax and Caspase-3 immunopositivities were higher in the CYP group than other groups. Conclusion: Our results show that quercetin has protective effect on cyclophosphamide-induced hepatotoxicity.
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