Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes.

Authors: Kemp, Daniel C; Zamek-Gliszczynski, Maciej J; Brouwer, Kim L R

Published In Toxicol Sci, (2005 Feb)

Abstract: Reports suggest that troglitazone, and to a lesser extent bosentan, may alter bile acid homeostasis by inhibiting the bile salt export pump. The present studies examined the hypothesis that these xenobiotics may modulate multiple hepatic bile acid transport mechanisms. In suspended rat hepatocytes, troglitazone (10 microM) decreased the initial rate of taurocholate uptake approximately 3-fold; the initial uptake rate of estradiol-17beta-D-glucuronide, a substrate of the organic anion transporting polypeptides, also was decreased approximately 4-fold. Bosentan (100 microM) decreased the initial uptake rate of taurocholate and estradiol-17beta-D-glucuronide by approximately 12- and approximately 7-fold, respectively. In sandwich-cultured rat hepatocytes, 10-min accumulation of taurocholate in cells + bile canaliculi (408 +/- 57 pmol/mg protein) was decreased significantly by troglitazone (157 +/- 17 pmol/mg protein, respectively) only in the presence of Na+, the driving force for the sodium taurocholate cotransporting polypeptide. A similar decrease with 10-fold higher concentrations of bosentan was noted. The biliary excretion index of taurocholate (55 +/- 8%) was decreased in the presence of 10 microM troglitazone (27 +/- 2%) and 100 microM bosentan (10 +/- 6%). In conclusion, xenobiotics may alter hepatic bile acid transport by inhibiting both hepatic uptake and biliary excretion.

PubMed ID: 15509663 Exiting the NIEHS site

MeSH Terms: Animals; Bile Canaliculi/drug effects*; Bile Canaliculi/metabolism; Cardiovascular Agents/toxicity*; Cells, Cultured; Chromans/toxicity*; Dose-Response Relationship, Drug; Drug Combinations; Hepatocytes/drug effects*; Hepatocytes/metabolism; Male; Rats; Rats, Wistar; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Sulfonamides/toxicity*; Taurocholic Acid/pharmacokinetics*; Thiazolidinediones/toxicity*

Back
to Top