In vitro interaction of drugs with canalicular lipid transporters
The liver is an essential organ for lipid homeostasis and metabolism as well as detoxification. Bile formation and biliary elimination of lipids (e.g., cholesterol) are key elements in lipid homeostasis and detoxification. Interference with bile formation (e.g., by drugs) may lead to acquired forms of liver disease. The major aim of Stieger’s project 12 is to establish an in vitro system for biliary lipid (phosphatidylcholine and cholesterol) secretion to test the hypothesis that selected drugs can interfere with biliary lipid secretion and consequently can cause (cholestatic) liver disease. The establishment of an in vitro model system based on a polar cell line is necessary as there is no experimental access to the canaliculus in vivo. The in vitro model for testing this hypothesis will be LLC-PK1 cells stably transfected with the hepatocellular sodium-taurocholate cotransporting polypeptide (NTCP), the bile salt export pump (BSEP), the phosphatidylcholine translocator multidrug resistance protein 3 (MDR3) and the cholesterol efflux mediator ABCG5/ABCG8. This cell line will be cultured in the Transwell® system.
University Hospital Zurich, Department of Clinical Pharmacology and Toxicology
|Mahdi Zainab (Ph.D. Student)
Stieger Bruno (PI)