TY - JOUR T1 - The Effects of Halofuginone and Ursodeoxycholic Acid in Prevention of Sclerosing Cholangitis Caused by Scolocidal Agents TT - Skolosidal Ajanlardan Kaynaklanan Sklerozan Kolanjitin Önlenmesinde Halofuginon ve Ursodeoksikolik Asidin Etkileri AU - Kocakuşak, Ahmet AU - Yıldırım, Doğan AU - Aktürk, Okan Murat AU - Çakır, Mikail AU - Sunamak, Oğuzhan AU - Hut, Adnan AU - Zengin, Abdullah Kağan AU - Özcan, Murat AU - Akı, Hilal AU - Balcı, Huriye PY - 2020 DA - May Y2 - 2019 DO - 10.17944/mkutfd.425288 JF - The Medical Journal of Mustafa Kemal University JO - mkutfd PB - Hatay Mustafa Kemal Üniversitesi WT - DergiPark SN - 2149-3103 SP - 26 EP - 30 VL - 11 IS - 39 LA - en AB - Aim:Biliarysclerosis is a life treatening condition caused by auto-immunity, operativetrauma, toxic agents, cancer and chronic inflammatory conditions. The liver tissue may progress into overt cirrhosisby the progression of fibrotic scar tissue. Halofuginone, which is the active component of theplant alkaloid febrifugine, has been shown to inhibit fibrosis.Material and Method:Fifty rats were randomizedon 5 groups to form a biliary sclerosis model by a scolocidal agent povidoneiodine(PI) injection into the common bile duct with a control group of salineinfusion included. The four PI groups were later treated by halofuginone, ursodeoxycholicacid (UDCA), with both and none. The rats were sacrificed 90 days later for intrahepaticand hilar fibrosis. Laboratory parameters of liver damage and levels ofhydroxypryroline to show collagen degradation were obtained and histologicalexamination of the liver and the common bile duct for fibrotic changes werecarried out.Results:With or without applicationof ursodeoxycholic acid, the halofuginone groups showed significantly lesssclerosis according to histological analysis. In regard to serum analysis of SGOT,SGPT and ALP; there were significantdifferences between “PI only” group and halofuginone groups. GGT was significantlyhigh in “PI only” group. There was not any significant difference between thegroups in regard to bilirubin levels. Hydroxyproline serum levels were highestin “PI only” group, followed by “UDCAonly” group and then halofuginone groups.Conclusion:Halofuginone was effectivein preventing fibrosis as an additional medical therapy to UDCA in an inducedsclerosing cholangitis model in rats. KW - Halofuginone KW - cirrhosis KW - ursodeoxycholic acid KW - sclerosing cholangitis KW - fibrosis KW - scolocidal N2 - Amaç:Biliyer skleroz,otoimmünite, operatif travma, toksik ajanlar, kanser ve kronik inflamatuvarkoşulların neden olduğu yaşamı tehdit eden durumdur. Karaciğer dokusu, fibrotikskar dokusunun ilerlemesi ile belirgin siroza doğru ilerleyebilir. Alkaloidfebrifugine bitkisinin aktif bileşeni olan halofuginonun, fibrozisi inhibe ettiğigösterilmiştir.Gereç ve Yöntemler:Elli sıçan, bir tanesisalin infüzyonu içeren bir kontrol grubu da içinde olmak üzere beş grubarandomize edilerek, koledoka skolosidal bir ajan olan povidon iyot (PI)enjeksiyonu ile bir biliyer skleroz modeli oluşturuldu. PI grupları (kontrolhariç tüm gruplar) daha sonra ya halofuginon, ya ursodeoksikolik asit (UDCA),ya ikisi beraber, ya da hiçbir madde verilmeyerek 90 gün takip edildi. Takipsonunda sıçanlar, intrahepatik ve hiler fibrozis tespiti için sakrifiye edildi.Karaciğer hasarının laboratuvar parametreleri ve kollajen degradasyonunugöstermek üzere hidroksiprolin düzeyleri serumda çalışıldı. Fibrotikdeğişikliklerin analizi için karaciğer ve koledokun histolojik incelemesiyapıldı.Bulgular:Ursodeoksikolik asitkullanılmış olsun veya olmasın, halofuginon kullanılan grupların histolojikanalizinde diğer gruplara göre istatistiksel açıdan alamlı derecede az sklerozmevcut idi. SGOT, SGPT ve ALP'nin serum analizleri incelendiğinde; "sadecePI kullanılan grup" ve halofuginon grupları arasında anlamlı farklılıklarvardı. GGT sadece PI kullanılan grup için anlamlı derecede yüksekti. Bilirubindüzeyleri açısından gruplar arasında anlamlı fark yoktu. Hidroksiprolin serumdüzeyleri "sadece PI kullanılan grup" için en yüksek olup, bunu sadeceUDCA kulanılan grup ve ardından halofuginon grupları izledi.Sonuç:Halofuginon, sıçanlardaindüklenen bir sklerozan kolanjit modelinde UDCA'ya ek bir tıbbi tedavi olarak karaciğerve safra yollarında fibrozun önlenmesinde etkili olmuştur. CR - Portmann B, Zen Y. 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Inhibition of collagen synthesis, smooth muscle cell proliferation, and injury-induced intimal hyperplasia by halofuginone. Arterioscler Thromb Vasc Biol 1997; 17: 194-202. UR - https://doi.org/10.17944/mkutfd.425288 L1 - https://dergipark.org.tr/tr/download/article-file/1110907 ER -