Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats.

Abstract

AIM:

To evaluate the protective effect of bicyclol against bile duct ligation (BDL)-induced hepatic fibrosis in rats.

METHODS:

Sprague-Dawley male rats underwent BDL and sham-operated animals were used as healthy controls. The BDL rats were divided into two groups which received sterilized PBS or bicyclol (100 mg/kg per day) orally for two consecutive weeks. Serum, urine and bile were collected for biochemical determinations. Liver tissues were collected for histological analysis and a whole genome oligonucleotide microarray assay. Reverse transcription-polymerase chain reaction and Western blotting were used to verify the expression of liver fibrosis-related genes.

RESULTS:

Treatment with bicyclol significantly reduced liver fibrosis and bile duct proliferation after BDL. The levels of alanine aminotransferase (127.7 ± 72.3 vs 230.4 ± 69.6, P < 0.05) and aspartate aminotransferase (696.8 ± 232.6 vs 1032.6 ± 165.8, P < 0.05) were also decreased by treatment with bicyclol in comparison to PBS. The expression changes of 45 fibrogenic genes and several fibrogenesis-related pathways were reversed by bicyclol in the microarray assay. Bicyclol significantly reduced liver mRNA and/or protein expression levels of collagen 1a1, matrix metalloproteinase 2, tumor necrosis factor, tissue inhibitors of metalloproteinases 2, transforming growth factor-β1 and α-smooth muscle actin.

CONCLUSION:

Bicyclol significantly attenuates BDL-induced liver fibrosis by reversing fibrogenic gene expression. These findings suggest that bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease.

• Authors: Yong-Zhan Zhen, Na-Ren Li, Hong-Wei He, Shuang-Shuang Zhao, Guang-Ling Zhang, Xiao-Fang Hao, Rong-Guang Shao
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 23 Pg. 7155-64 (Jun 21 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 26109801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Biphenyl Compounds
• bicyclol

Topics

• Animals
• Bile (metabolism)
• Bile Ducts (surgery)
• Biomarkers (blood, urine)
• Biphenyl Compounds (pharmacology)
• Cell Proliferation (drug effects)
• Cytoprotection
• Disease Models, Animal
• Gene Expression Profiling (methods)
• Gene Expression Regulation
• Ligation
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Biliary (etiology, genetics, metabolism, pathology, prevention & control)
• Male
• Rats, Sprague-Dawley