title: Model Systems for Studying the Role of Canalicular Efflux Transporters in Drug-Induced Cholestatic Liver Disease.
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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland. Electronic address: bruno.stieger@uzh.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
authors.forename: Zainab M
authors.initials: ZM
authors.lastname: Mahdi
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D002779:Cholestasis / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins
keywords: ABC transporters; Bile acid transporters; Drug interactions; Hepatic transport; Transporters