.: ORİJİNAL ARAŞTIRMA
The Efficacy of 5-Fluorouracil Therapy on Liver Fibrosis in Rats: Experimental Study
Sıçanlarda Karaciğer Fibrozu Üzerine 5-Florourasil Tedavisinin Etkinliği: Deneysel Çalışma
Turkiye Klinikleri J Med Sci. 2022;42(1):14-20
doi: 10.5336/medsci.2021-84679
Makale Dili: EN
Tam Metin
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
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
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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