Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

作     者：Tomomichi Iwaki Kaoru Ishizaki Shuji Kinoshita Hideki Tanaka Atsushi Fukunari Makoto Tsurufuji Teruaki Imada 

作者机构：Research Laboratory Ⅲ (Immunology) Pharmaceuticals Research Division Mitsubishi Pharma Corporation Yokohama Japan Pharmacokinetics Laboratory Pharmaceuticals Research Division Mitsubishi Pharma Corporation Chiba Japan Discovery Technology Laboratory Pharmaceuticals Research Division Mitsubishi Pharma Corporation Yokohama Japan 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第37期

页      面：5003-5008页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Chenodeoxycholic acid Hamster Liver bileacids Ursodeoxycholic acid 

摘      要：AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver. METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment. RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved. CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.