Sıçanlarda ursodeoksikolik asidin hepatik yağlanma üzerine etkisi

Abstract

Oz Ursodeoksikolik asid (UDKA)'in çeşitli karaciğer hastalıklarında hepatoprotektif etkilere sahip olduğu gösterilmiştir. Bu ilacın, hepatik yağlanma (HY)'yı azaltarak nonalkolik steatohepatitli hastalarda da etkili olduğu bulunmuştur. Bu çalışmanın amacı UDKA'nın sıçanlarda hem HY'yı önlemede, hem de oluşmuş yağlanmayı geriletmede etkili olup olmadığını araştırmaktı. Karaciğerde yağlı değişiklikleri indüklemek için `kolinden eksik diyet` diyet (KED) kullanıldı. UDKA verilecek sıçanlar için, %1.5'luk UDKA solüsyonu oral bir `feeding` tfibü kullanarak 25 mg/kg/gün dozunda verildi. HY'nın değerlendirilmesi, lipid vakuolleri içeren hepatositlerin yüzdesinin hesaplanmasıyla yapıldı. 43 wistar tipi erkek sıçan rasgele olarak iki protokole ayrıldı. Protokol I'de 7 sıçana 30 gün süreyle bazal diyet (BD) + UDKA verildi [kontrol grubu]. Protokol H'de; 30 gün süreyle 19 sıçan KED ile, 17 sıçan ise KED + UDKA ile beslendi. Bu sürenin sonunda sıçanlara karaciğer biyopsileri uygulandıktan sonra; hem KED, hem de KED + UDKA verilenlerde gelişen steatoz dereceleri bilinmeksizin 30 gün süreyle ya BD, ya da BD + UDKA'ya başlandı. Bu sürenin sonunda, UDKA'nın HY'yı geriletmede etkisinin olup olmadığını değerlendirmek için karaciğer biyopsileri tekrarlandı. Protokol I'de 30 gün sonunda karaciğerin histolojik muayenesinde spesifik bulgular yoktu. Protokol Il'de; KED ile beslenen 19 sıçanın 7'sinde %10'un üzerinde HY gelişmişken, KED + UDKA ile beslenen 17 sıçanın yalnızca 3'ünde %10'un üzerinde HY gelişmişti. KED + UDKA ile beslenen sıçanlarda HY yüzdesi aynı periyod sonunda yalnızca KED ile beslenen sıçanlardan anlamlı bir şekilde daha düşüktü (HY%'si; ortalama+standart sapma: sırasıyla, 12.2+29.6'ya karşı 23.2+34.1, p=0.0201). Karaciğerinde yağlı değişiklikler gelişen tüm sıçanlarda; hem BD, hem de BD + UDKA başlandıktan 30 gün sonra HYhemen hemen tamamen gerilemişti. Sonuç olarak UDKA, sıçanlarda HY'yı önlüyor gibi gözükmektedir; BD'e UDKA ilavesi HY'yı geriletmede ek bir katkı sağlamamaktadır. Anahtar kelimeler: Hepatik yağlanma, ursodeoksikolik asid Abstract Ursodeoxycholic acid (UDCA) has been shown to have hepatoprotective effects in various liver diseases. This drug has also been found to be effective in patients with nonalcoholic steatohepatitis, improving hepatic steatosis (HS) significantly. The aim of this study was to evaluate whether UDCA has an effect in both preventing and regressing HS in rats. To induce fatty liver, choline deficient diet (CDD) was used. For the rats assigned to receive UDCA, l.S % UDCA solution was administered in a dose of 25 mg/kg/day using an oral feeding tube. Assesment of HS was based on the quantification of percentage of hepatocytes containing lipid vacuoles. Forty-three male wistar rats were randomly divided into two protocols. In the protocol I, 7 rats were fed with a basal diet (BD) plus UDCA for 30 days (control group]. In the protocol H, 19 rats were fed with CDD and 17 rats were fed with CDD plus UDCA for 30 days. At the end of this period, after performing liver biopsies, either BD or BD plus UDCA was started in both CDD-fed rats and CDD plus UDCA-fed rats for 30 days at random without knowing their degree of steatosis developed. At the end of this period, the liver biopsies were repeated in order to evaluate whether UDCA has an effect on the regression of HS. In protocol I, there were not specific findings on the histological examination of the livers at 30 days. In protocol II, HS over 10% developed in 7 of 19 CDD fed-rats, while developing in only 3 of 17 CDD plus UDCA-fed rats, and the percentage of HS in CDD plus UDCA-fed rats was significantly lower than CDD-fed rats at the end of the same period (% of steatosis, mean+standard deviation: 12.2+29.6 to 23.2+34.1 respectively, p=0.0201); after starting either BD or BD plus UDCA, steatosis was almost completely

hemen hemen tamamen gerilemişti. Sonuç olarak UDKA, sıçanlarda HY'yı önlüyor gibi gözükmektedir; BD'e UDKA ilavesi HY'yı geriletmede ek bir katkı sağlamamaktadır. Anahtar kelimeler: Hepatik yağlanma, ursodeoksikolik asid Abstract Ursodeoxycholic acid (UDCA) has been shown to have hepatoprotective effects in various liver diseases. This drug has also been found to be effective in patients with nonalcoholic steatohepatitis, improving hepatic steatosis (HS) significantly. The aim of this study was to evaluate whether UDCA has an effect in both preventing and regressing HS in rats. To induce fatty liver, choline deficient diet (CDD) was used. For the rats assigned to receive UDCA, l.S % UDCA solution was administered in a dose of 25 mg/kg/day using an oral feeding tube. Assesment of HS was based on the quantification of percentage of hepatocytes containing lipid vacuoles. Forty-three male wistar rats were randomly divided into two protocols. In the protocol I, 7 rats were fed with a basal diet (BD) plus UDCA for 30 days (control group]. In the protocol H, 19 rats were fed with CDD and 17 rats were fed with CDD plus UDCA for 30 days. At the end of this period, after performing liver biopsies, either BD or BD plus UDCA was started in both CDD-fed rats and CDD plus UDCA-fed rats for 30 days at random without knowing their degree of steatosis developed. At the end of this period, the liver biopsies were repeated in order to evaluate whether UDCA has an effect on the regression of HS. In protocol I, there were not specific findings on the histological examination of the livers at 30 days. In protocol II, HS over 10% developed in 7 of 19 CDD fed-rats, while developing in only 3 of 17 CDD plus UDCA-fed rats, and the percentage of HS in CDD plus UDCA-fed rats was significantly lower than CDD-fed rats at the end of the same period (% of steatosis, mean+standard deviation: 12.2+29.6 to 23.2+34.1 respectively, p=0.0201); after starting either BD or BD plus UDCA, steatosis was almost completelyregressed at 30 days in all rats developed steatogenic changes. In conclusion, UDCA seems to prevent HS in rats; addition of UDCA to BD does not cause a further contribution in regressing HS. Key words: Hepatic steatosis, ursodeoxycholic acid