Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7155
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
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.
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.