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Arzneimittelforschung 2011; 61(3): 173-179
DOI: 10.1055/s-0031-1296185
Liver Therapeutics
Editio Cantor Verlag Aulendorf (Germany)

Beneficial effects of colchicine on 17α-ethynylestradiol-induced cholestasis in rats

Zhi-Xing Zhou
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
5   These authors contributed equally to this work.
,
Tao Wang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
2   Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China
5   These authors contributed equally to this work.
,
Zhen-Zhou Jiang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
3   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
,
Jing Shang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Li Liu
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
4   Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, P. R. China
,
Yue Zhang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Dan Zhu
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Xiao Huang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Shuang Zhang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Yue Hu
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Jia-Ying Wang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Lu-Yong Zhang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
2   Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China
› Author Affiliations
Further Information

Publication History

Publication Date:
28 November 2011 (online)

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Abstract

Colchicine (CAS 64-86-8) is considered to have a hepatoprotective effect and play a role in biliary excretion. 17a-Ethynyl-estradiol (EE) (5 mg/kg, subcutaneously, daily, for 5 days) causes intrahepatic cholestasis by reducing both the influx and efflux of bile acid in hepatocytes, resulting in a decrease in bile flow. The objective of this study was to evaluate whether colchicine has any effect on EE-induced cholestasis. The effects of colchicine treatment on EE-induced cholestasis in rats for 5 consecutive days were evaluated. The serum components and enzymatic activity were assayed. In addition, the bile flow and biliary excretion were determined. Furthermore, western blot analysis was used to measure the expression of farnesoid X receptor (FXR), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and cholesterol 7α-hydroxylase (CYP7A1). Colchicine not only significantly inhibited the elevation of cholestasis-related serum components and enzyme activity but also significantly attenuated the decrease of the bile flow and biliary excretion. Colchicine also remarkably increased the hepatic expression of FXR, BSEP and MRP2, but decreased that of CYP7A1. Our data indicates that colchicine treatment attenuated EE-induced cholestasis in rats, most likely by promoting bile flow and biliary excretion, and reduced the synthesis of bile acids.

Key words

Bile salt export pump - CAS 64-86-8 - Cholestasis - Cholesterol 7α-hydroxylase - Colchicine - Farnesoid X receptor - Multidrug resistance-associated protein 2
 

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