Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2015; 21(23): 7155-7164
Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7155
Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats
Yong-Zhan Zhen, Na-Ren Li, Hong-Wei He, Shuang-Shuang Zhao, Guang-Ling Zhang, Xiao-Fang Hao, Rong-Guang Shao
Yong-Zhan Zhen, Guang-Ling Zhang, Xiao-Fang Hao, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, Hebei United University, Tangshan 063000, Hebei Province, China
Na-Ren Li, Hong-Wei He, Shuang-Shuang Zhao, Rong-Guang Shao, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Author contributions: Zhen YZ and Li NR contributed equally to this work; He HW and Shao RG designed and supervised the study; Zhen YZ, Zhang GL and Hao XF performed animal experiments and collected samples; Li NR, He HW and Zhao SS conducted in-depth research and acquired and analyzed the data; Zhen YZ drafted and revised the manuscript; Li NR, He HW and Shao RG revised the manuscript for important intellectual content; all the authors have read and approved the final version to be published.
Supported by the National Natural Science Foundation of China, No. 81170409, No. 81201281; the National S&T Major Special Project on Major New Drug Innovation, No. 2012ZX09301002-001; and the Wang Bao En Liver Fibrosis Foundation, No. 20110026.
Ethics approval: This study was reviewed and approved by the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Hebei United University.
Conflict-of-interest: The authors declare no conflict of interests.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong-Wei He, Associate Professor, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Tian Tan Xi Li, Dongcheng District, Beijing 100050, China. hehwei@imb.pumc.edu.cn
Telephone: +86-10-83166673 Fax: +86-10-63017302
Received: January 3, 2015
Peer-review started: January 4, 2015
First decision: January 22, 2015
Revised: February 13, 2015
Accepted: April 9, 2015
Article in press: April 9, 2015
Published online: June 21, 2015
Processing time: 168 Days and 0.9 Hours
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.

Keywords: Bicyclol; Rat; Bile duct ligation; Liver fibrosis; Gene expression profile

Core tip: Cholestasis often fails to respond to medical therapy, resulting in liver necrosis, fibrosis, cirrhosis and subsequent liver failure. Bicyclol has significant liver protective effects but little is known about the effect of this drug on cholestatic liver fibrosis. Therefore, the present study was designed to investigate the protective effects of bicyclol in a rat model of liver fibrosis induced by bile duct ligation (BDL). Bicyclol can improve liver function after BDL and decrease bile duct proliferation, inflammation and fibrosis. Bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease.