Sıçanlarda 5-Fluorourasil ile Oluşturulmuş Gastrointestinal Mukozitte Berberinin Terapötik Etkisi

Öz

Çalışmamızda, sıçanlara 5-florourasil uygulanması ile oluşturulan gastrointestinal mukoza hasarına karşı berberinin terapötik potansiyelinin araştırılması. Gereç ve Yöntem: Çalışmada 6-8 haftalık Wistar Albino erkek sıçanlar kontrol, 5FU, BER75, BER150 ve BER300 olarak 5 gruba ayrılmıştır (n=8/grup). 5FU, BER75, BER150 ve BER300 gruplarına 0-7. günler arasında gün aşırı 5-FU (60 mg/kg, ip) uygulanarak mukozit oluşturuldu. BER75, BER150 ve BER300 gruplarına sırasıyla 75, 150 ve 300 mg/kg/gün dozlarda berberin yine 0-7. günler arasında hergün po uygulandı. Deneyin başında ve sonunda hayvanların vücut ağırlıkları ölçüldü. Total antioksidan aktivite (TAS), total oksidan aktivite (TOS), TNF-α, IL-6 ve NF-κB düzeylerinin serumda tayinleri için ELISA yöntemi kullanıldı. Jejenum ve ileum doku kesitlerinde histopatolojik değerlendirme yapıldı. Bulgular: Deneyin sonunda hayvanların vücut ağırlıklarındaki yüzde değişimi (%VA) tedavi gruplarında kontrol grubuna göre anlamlı derecede daha düşüktü (her biri için p ˂0,001), ancak berberin tedavisi 5-FU’in oluşturduğu kilo kaybını düzeltmemiştir. Oksidatif stres indeks değerleri açısından gruplar arasında anlamlı fark bulunamadı (p >0,05). IL-6 düzeyi 5FU grubuna kıyasla BER75 grubunda hafif, BER150 ve BER300 gruplarında anlamlı derecede azaldı (sırasıyla, p>0,05; p=0,002 ve p=0,002). TNF-α düzeyi 5-FU grubuna kıyasla BER75, BER150 ve BER300 gruplarında azaldı (sırasıyla p> 0,05; p=0,003; p> 0,05). NF-κB düzeyi kontrol grubuna kıyasla 5FU grubunda bir miktar yüksek bulunmuştur (p> 0,05). BER75, BER150 ve BER300 gruplarında ise anlamlı derecede azaldı (sırasıyla p<0.05, p<0,001 ve p<0.05). Histopatolojik olarak 5-FU grubunda yoğun epitel hasarı, inflamatuvar hücre infiltrasyonu, kanama ve ödem odakları görüldü. Tedavi gruplarında ise berberinin doz bağımlı bir şekilde bu hasarı azalttığı tespit edildi. Sonuç: Berberinin doz bağımlı olarak sıçanlarda 5-florourasil ile oluşturulan gastrointestinal mukozitte potansiyel bir terapötik ajan olabileceği düşünülmektedir.

Anahtar Kelimeler

• 5-Florourasil
• Berberin
• gastrointestinal mukozit
• invivo

The Potential Effect of Berberine on 5-Fluorouracil Induced Gastrointestinal Mucositis in Rats

Öz

5-Fluorouracil (5-FU), an antineoplastic agent, causes intestinal mucositis (IM) that limits the drug efficacy. The aim of this study was to reveal the protective and/or therapeutic effects of berberine (BER), an isoquinoline quaternary alkaloid, on IM induced by 5-FU in rats. Forty Wistar albino male rats were randomly divided into five groups: Control, 5-FU, 5-FU+BER75 (75 mg/kg/day), 5-FU+BER150 (150 mg/kg/day) and 5-FU+BER300 (300 mg/kg/day). 5-FU was intraperitoneally (i.p) injected at a dose of 60 mg/kg on alternate days for 4 days, while other groups were orally received BER daily for 7 days. By the end of study, intracardiac blood samples were collected and intestinal tissues were removed for histological examination. TNF-α, IL-6 and NF-κB levels were measured in serum using commercial ELISA kits. Results showed that BER at increasing doses ameliorated body weight loss and histopathological damage. It was concluded that BER may be effective in the treatment and/or prophylaxis of the damage in the gastrointestinal system caused by 5-FU in a dose-dependent manner.

Anahtar Kelimeler

• 5-Fluorouracil
• Berberine
• gastrointestinal mucositis
• in vivo

Kaynakça

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