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Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters
Tomomichi Iwaki1, Kaoru Ishizaki, Shuji Kinoshita
1Research 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
Insights
Ursodeoxycholic acid (UDCA) protects hamsters from liver injury caused by chenodeoxycholic acid (CDCA). UDCA reduces toxic bile acid accumulation, improving liver health.
Area of Science:
- Hepatology
- Toxicology
- Gastroenterology
Background:
- Chenodeoxycholic acid (CDCA) is a hydrophobic bile acid that can induce liver injury.
- Elevated levels of hydrophobic bile acids are associated with liver damage and cytotoxicity.
- Understanding the protective mechanisms of bile acids is crucial for managing liver diseases.
Purpose of the Study:
- To evaluate the protective effects of ursodeoxycholic acid (UDCA) against CDCA-induced liver injury in a hamster model.
- To investigate the correlation between liver injury markers and bile acid profiles in the liver.
- To elucidate the mechanism by which UDCA mitigates CDCA-induced hepatotoxicity.
Main Methods:
- Liver injury was induced in hamsters by oral administration of 0.5% CDCA in feed for 7 days.
- Ursodeoxycholic acid (UDCA) was administered at doses of 50 mg/kg and 150 mg/kg for the final 3 days of the experiment.
- Liver histology and serum alanine aminotransferase (ALT) levels were assessed to confirm and quantify liver injury. Bile acid profiles in the liver were analyzed.
Main Results:
- CDCA administration significantly increased serum ALT levels (over 10-fold) and caused histological evidence of liver injury.
- A marked increase in total and hydrophobic bile acids, including CDCA and lithocholic acid (LCA), was observed in the liver.
- UDCA treatment dose-dependently reduced serum ALT levels and improved liver histology, with significant reductions observed at both 50 mg/kg and 150 mg/kg doses.
- UDCA decreased the hepatic concentrations of hydrophobic bile acids, leading to a reduction in overall liver bile acid levels.
Conclusions:
- Ursodeoxycholic acid (UDCA) demonstrates significant protective effects against oral CDCA-induced liver damage in hamsters.
- The hepatoprotective mechanism of UDCA involves the reduction of cytotoxic hydrophobic bile acids, such as CDCA and LCA, in the liver.
- These findings highlight UDCA's potential therapeutic role in managing liver conditions associated with bile acid dysregulation.
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.