title: Beneficial effects of colchicine on 17alpha-ethynylestradiol-induced cholestasis in rats.
abstract: Colchicine (CAS 64-86-8) is considered to have a hepatoprotective effect and play a role in biliary excretion. 17alpha-Ethynylestradiol (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 7alpha-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.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Wang
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002779:Cholestasis / Q000139:chemically induced* / Q000188:drug therapy*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D003078:Colchicine / Q000627:therapeutic use*; D004798:Enzymes / Q000097:blood; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol; D006074:Gout Suppressants / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D003078:Colchicine; D004798:Enzymes; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol; D006074:Gout Suppressants; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C490548:Abcb11 protein, rat; C423013:Abcc2 protein, rat; C532838:CYP7A1 protein, rat