Computational Toxicology

Chapter 6Transporters in Hepatotoxicity

Eleni Kotsampasakou, Sankalp Jain, Daniela Digles and Gerhard F. Ecker

Department of Pharmaceutical Chemistry, University of Vienna, Wien, Austria

Chapter Menu

1. Introduction
2. Basolateral Transporters
3. Canalicular Transporters
4. Data Sources for Transporters in Hepatotoxicity
5. In Silico Transporters Models
6. Ligand-Based Approaches
7. OATP1B1 and OATP1B3
8. NTCP
9. OCT1
10. OCT2
11. MRP1, MRP3, and MRP4
12. BSEP
13. MRP2
14. MDR1/P-gp
15. MDR3
16. BCRP
17. MATE1
18. ASBT
19. Structure-Based Approaches
20. Complex Models Incorporating Transporter Information
21. In Vitro Models
22. Multiscale Models
23. Outlook

6.1 Introduction

Transmembrane transporters are essential for regulation of the uptake and efflux of endobiotics and xenobiotics at the cellular level as well as in barrier tissues (e.g., blood–brain barrier, kidney, liver, enterocytes). Among them, hepatic transporters possess a vital role, as the liver is the main organ of metabolism and detoxification [1, 2]. Figure 6.1 depicts the main hepatic transporters and their respective location in the hepatocyte. In the following section, we will briefly introduce their significance in selected liver toxicity manifestations.

Figure 6.1 Transporters located in the hepatocyte. The medium grey symbols represent the canalicular transporters and dark grey ones the basolateral transporters. Cycles represent uptake transporters and ellipses refer to efflux transporters. ...