Doğan YILDIRIM, Okan Murat AKTÜRK, Ahmet KOCAKUŞAK, Mikail ÇAKIR, Oğuzhan SUNAMAK, Adnan HUT, Abdullah Kağan ZENGİN, Murat ÖZCAN, Hilal AKI, Huriye BALCI

Skolosidal Ajanlardan Kaynaklanan Sklerozan Kolanjitin Önlenmesinde Halofuginon ve Ursodeoksikolik Asidin Etkileri

Amaç: Biliyer skleroz, otoimmünite, operatif travma, toksik ajanlar, kanser ve kronik inflamatuvar koşulların neden olduğu yaşamı tehdit eden durumdur. Karaciğer dokusu, fibrotik skar dokusunun ilerlemesi ile belirgin siroza doğru ilerleyebilir. Alkaloid febrifugine bitkisinin aktif bileşeni olan halofuginonun, fibrozisi inhibe ettiği gösterilmiştir.Gereç ve Yöntemler: Elli sıçan, bir tanesi salin infüzyonu içeren bir kontrol grubu da içinde olmak üzere beş gruba randomize edilerek, koledoka skolosidal bir ajan olan povidon iyot (PI) enjeksiyonu ile bir biliyer skleroz modeli oluşturuldu. PI grupları (kontrol hariç tüm gruplar) daha sonra ya halofuginon, ya ursodeoksikolik asit (UDCA), ya ikisi beraber, ya da hiçbir madde verilmeyerek 90 gün takip edildi. Takip sonunda sıçanlar, intrahepatik ve hiler fibrozis tespiti için sakrifiye edildi. Karaciğer hasarının laboratuvar parametreleri ve kollajen degradasyonunu göstermek üzere hidroksiprolin düzeyleri serumda çalışıldı. Fibrotik değişikliklerin analizi için karaciğer ve koledokun histolojik incelemesi yapıldı.Bulgular: Ursodeoksikolik asit kullanılmış olsun veya olmasın, halofuginon kullanılan grupların histolojik analizinde diğer gruplara göre istatistiksel açıdan alamlı derecede az skleroz mevcut idi. SGOT, SGPT ve ALP'nin serum analizleri incelendiğinde; "sadece PI kullanılan grup" ve halofuginon grupları arasında anlamlı farklılıklar vardı. GGT sadece PI kullanılan grup için anlamlı derecede yüksekti. Bilirubin düzeyleri açısından gruplar arasında anlamlı fark yoktu. Hidroksiprolin serum düzeyleri "sadece PI kullanılan grup" için en yüksek olup, bunu sadece UDCA kulanılan grup ve ardından halofuginon grupları izledi.Sonuç: Halofuginon, sıçanlarda indüklenen bir sklerozan kolanjit modelinde UDCA'ya ek bir tıbbi tedavi olarak karaciğer ve safra yollarında fibrozun önlenmesinde etkili olmuştur.

Anahtar Kelimeler:

Halofuginon, siroz, ursodeoksikolik asit, sklerozan kolanjit, fibrozis, skolosidal

The Effects of Halofuginone and Ursodeoxycholic Acid in Prevention of Sclerosing Cholangitis Caused by Scolocidal Agents

Aim: Biliary sclerosis is a life treatening condition caused by auto-immunity, operative trauma, toxic agents, cancer and chronic inflammatory conditions. The liver tissue may progress into overt cirrhosis by the progression of fibrotic scar tissue. Halofuginone, which is the active component of the plant alkaloid febrifugine, has been shown to inhibit fibrosis. Material and Method: Fifty rats were randomized on 5 groups to form a biliary sclerosis model by a scolocidal agent povidone iodine(PI) injection into the common bile duct with a control group of saline infusion included. The four PI groups were later treated by halofuginone, ursodeoxycholic acid (UDCA), with both and none. The rats were sacrificed 90 days later for intrahepatic and hilar fibrosis. Laboratory parameters of liver damage and levels of hydroxypryroline to show collagen degradation were obtained and histological examination of the liver and the common bile duct for fibrotic changes were carried out. Results: With or without application of ursodeoxycholic acid, the halofuginone groups showed significantly less sclerosis according to histological analysis. In regard to serum analysis of SGOT, SGPT and ALP; there were significant differences between “PI only” group and halofuginone groups. GGT was significantly high in “PI only” group. There was not any significant difference between the groups in regard to bilirubin levels. Hydroxyproline serum levels were highest in “PI only” group, followed by “UDCA only” group and then halofuginone groups.Conclusion: Halofuginone was effective in preventing fibrosis as an additional medical therapy to UDCA in an induced sclerosing cholangitis model in rats.

Keywords:

Halofuginone, cirrhosis, ursodeoxycholic acid, sclerosing cholangitis, fibrosis, scolocidal,

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