title: Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Yong-Zhan
authors.initials: YZ
authors.lastname: Zhen
authors.affiliation: 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.
authors.forename: Na-Ren
authors.initials: NR
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: He
authors.affiliation: 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.
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Guang-Ling
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Hao
authors.affiliation: 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.
authors.forename: Rong-Guang
authors.initials: RG
authors.lastname: Shao
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001713:Biphenyl Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D001713:Biphenyl Compounds; C477843:bicyclol
keywords: Bicyclol; Bile duct ligation; Gene expression profile; Liver fibrosis; Rat