Model Systems for Studying the Role of Canalicular Efflux Transporters in Drug-Induced Cholestatic Liver Disease

J Pharm Sci. 2017 Sep;106(9):2295-2301. doi: 10.1016/j.xphs.2017.03.023. Epub 2017 Apr 3.

Abstract

Bile formation is a key function of the liver. Disturbance of bile flow may lead to liver disease and is called cholestasis. Cholestasis may be inherited, for example, in progressive familial intrahepatic cholestasis or acquired, for example, by drug-mediated inhibition of bile salt export from hepatocytes into the canaliculi. The key transport system for exporting bile salts into the canaliculi is the bile salt export pump. Inhibition of the bile salt export pump by drugs is a well-established cause of drug-induced cholestasis. Investigation of the role of the multidrug resistance protein 3, essential for biliary phospholipid secretion, is emerging now. This overview summarizes current concepts and methods with an emphasis on in vitro model systems for the investigation of drug-induced cholestasis in the general context of drug-induced liver injury.

Keywords: ABC transporters; Bile acid transporters; Drug interactions; Hepatic transport; Transporters.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Cholestasis / metabolism*
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism*
  • Membrane Transport Proteins / metabolism*

Substances

  • Membrane Transport Proteins