Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2007; 13(37): 5003-5008
Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.5003
Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters
Tomomichi Iwaki, Kaoru Ishizaki, Shuji Kinoshita, Hideki Tanaka, Atsushi Fukunari, Makoto Tsurufuji, Teruaki Imada
Tomomichi Iwaki, Kaoru Ishizaki, Teruaki Imada, Research Laboratory III (Immunology), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, Yokohama 227-0033, Japan
Shuji Kinoshita, Pharmacokinetics Laboratory, Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, Chiba, Japan
Hideki Tanaka, Atsushi Fukunari, Makoto Tsurufuji, Discovery Technology Laboratory, Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, Yokohama 227-0033, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Tomomichi Iwaki, Research Laboratory III (Immunology), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. iwaki.tomomichi@mh.m-pharma.co.jp
Telephone: +81-45-9634739 Fax: +81-45-9634641
Received: April 5, 2007
Revised: July 12, 2007
Accepted: July 26, 2007
Published online: October 7, 2007
Abstract

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 (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.

Keywords: Chenodeoxycholic acid; Hamster; Liver bile acids; Ursodeoxycholic acid