Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
The Efficacy of 5-Fluorouracil Therapy on Liver Fibrosis in Rats: Experimental Study
Sıçanlarda Karaciğer Fibrozu Üzerine 5-Florourasil Tedavisinin Etkinliği: Deneysel Çalışma
Gökhan OKAYa, Levent DUMANa, İbrahim Metin ÇİRİŞb, İlter İLHANc, Hülya METE ARICANc, Adnan KARAİBRAHİMOĞLUd
aDepartment of Pediatric Surgery, Süleyman Demirel University Faculty of Medicine, Isparta, TURKIYE
bDepartment of Pathology, Süleyman Demirel University Faculty of Medicine, Isparta, TURKIYE
cDepartment of Biochemistry, Süleyman Demirel University Faculty of Medicine, Isparta, TURKIYE
dDepartment of Biostatistics and Medical Informatics, Süleyman Demirel University Faculty of Medicine, Isparta, TURKIYE
Turkiye Klinikleri J Med Sci. 2022;42(1):14-20
doi: 10.5336/medsci.2021-84679
Article Language: EN
Full Text
ABSTRACT
 Objective: Liver fibrosis is a common pathological condition that can lead to liver failure. Previous studies demonstrated that 5-fluorouracil (5-FU) is an effective agent in preventing fibrosis. This experimental study aimed to evaluate the efficacy of 5-FU therapy on liver fibrosis in rats. Material and Methods: Thirty-eight rats were divided into 3 groups: Group 1 (sham-operated, n=10), the bile duct (BD) was exposed but not ligated; Group 2 [bile duct ligation (BDL)-saline, n=14], the BD was ligated and normal saline solution was given; Group 3 (BDL-5-FU, n=14), the BD was ligated and treated with 5-FU. The liver and blood samples were harvested at postoperative day 21. Liver function analyses, tissue hydroxyproline (HP) content, and serum and tissue transforming growth factor beta 1 (TGF-β1) levels were determined. The liver sections were analyzed and percentage of tissue collagen content was measured. Results: There were no significant differences between the groups in terms of tissue (p=0.748) and serum (p=0.123) levels of TGF-β1. Mean HP level in the sham-operated, BDL-saline, and BDL-5-FU groups were 253±42 ng/L, 360±32 ng/L and 305±41 ng/L, respectively. 5-FU significantly decreased HP level (p=0.036). Mean percentage of collagen content in the sham-operated, BDL-saline, and BDL-5-FU groups were 0.99±0.39%, 4.92±1.03%, and 2.62±0.64%, respectively. 5-FU significantly reduced collagen accumulation (p<0.001). Conclusion: 5-FU has a preventive effect on liver fibrosis in rats. This result suggests that 5-FU can be a potential agent for prevention of liver fibrosis in clinical practice.

Keywords: 5-fluorouracil; liver; fibrosis
ÖZET
 Amaç: Karaciğer fibrozu, karaciğer yetersizliğine yol açabilen yaygın bir patolojik durumdur. Önceki çalışmalar, 5-florourasilin (5- FU) fibrozu önlemede etkili bir ajan olduğunu göstermiştir. Bu deneysel çalışmada, sıçanlarda 5-FU tedavisinin karaciğer fibrozu üzerindeki etkinliğinin araştırılması amaçlandı. Gereç ve Yöntemler: Otuz sekiz sıçan 3 gruba ayrıldı: Grup 1 (sham ameliyatı, n=10), safra kanalı (SK) açığa çıkarıldı ancak bağlanmadı; Grup 2 [safra kanalı ligasyonu (SKL)-salin, n=14], SK bağlandı ve normal salin solüsyonu verildi; Grup 3 (SKL-5-FU, n=14), SK bağlandı ve 5-FU ile tedavi edildi. Karaciğer ve kan örnekleri postoperatif 21. günde alındı. Karaciğer fonksiyon analizleri, doku hidroksiprolin (HP) içeriği, serum ve doku dönüştürücü büyüme faktörü beta 1 [transforming growth factor beta 1 (TGF-β1)] düzeyleri biyokimyasal olarak belirlendi. Karaciğer kesitleri analiz edildi ve doku kollajen içeriği yüzdesi ölçüldü. Bulgular: Doku (p=0,748) ve serum (p=0,123) TGF-β1 düzeyleri açısından gruplar arasında anlamlı fark yoktu. Sham ameliyatı, SKL-salin ve SKL-5-FU gruplarında ortalama HP seviyeleri sırasıyla 253±42 ng/L, 360±32 ng/L ve 305±41 ng/L idi. 5-FU tedavisi HP düzeyini anlamlı olarak düşürdü (p=0,036). Sham ameliyatı, SKL-salin ve SKL-5-FU gruplarında ortalama kollajen içeriği yüzdeleri sırasıyla %0,99±0,39, %4,92±1,03 ve %2,62±0,64 idi. 5-FU tedavisi kollajen birikimini önemli ölçüde azalttı (p<0,001). Sonuç: 5-FU, sıçanlarda karaciğer fibrozu üzerinde önleyici bir etkiye sahiptir. Bu sonuç, 5-FU'nun klinik uygulamada karaciğer fibrozunun önlenmesi için potansiyel bir ajan olabileceğini düşündürmektedir.

Anahtar Kelimeler: 5-florourasil; karaciğer; fibrozis
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