Skolosidal Ajanlardan Kaynaklanan Sklerozan Kolanjitin Önlenmesinde Halofuginon ve Ursodeoksikolik Asidin Etkileri

Yıl 2020, Cilt: 11 Sayı: 39, 26 - 30, 19.05.2020

Doğan Yıldırım Okan Murat Aktürk , Ahmet Kocakuşak , Mikail Çakır Oğuzhan Sunamak , Adnan Hut , Abdullah Kağan Zengin Murat Özcan Hilal Akı Huriye Balcı

https://doi.org/10.17944/mkutfd.425288

Öz

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

Öz

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.

Anahtar Kelimeler

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

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