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

被引:14
作者
Iwaki, Tomomichi
Ishizaki, Kaoru
Kinoshita, Shuji
Tanaka, Hideki
Fukunari, Atsushi
Tsurufuji, Makoto
Imada, Teruaki
机构
[1] Mitsubishi Pharma Corp, Div Pharmaceut Res, Aoba Ku, Res Lab Immunol 3, Yokohama, Kanagawa 2270033, Japan
[2] Mitsubishi Pharma Corp, Div Pharmaceut Res, Pharmacokinet Lab, Yokohama, Kanagawa 2270033, Japan
[3] Mitsubishi Pharma Corp, Div Pharmaceut Res, Discovery Technol Lab, Yokohama, Kanagawa 2270033, Japan
关键词
chenodeoxycholic acid; hamster; liver bile acids; ursocleoxycholic acid;
D O I
10.3748/wjg.v13.i37.5003
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To investigate the effects of ursocleoxycholic 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 (ALT) 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. (c) 2007 WJG. All rights reserved.
引用
收藏
页码:5003 / 5008
页数:6
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