Rationale for the research area
The liver is one of the main targets of toxicants such as drugs and other chemicals. The main reasons are that after oral ingestion, chemicals can reach high concentrations in the liver and metabolites can be produced, which may be toxic. Drug-associated liver injury is one of the most important reasons for unsuccessful drug development or withdrawal from the market.
The main objectives of this project are:
- Development and characterization of cell systems and animal models to test drugs and chemicals for hepatotoxicity
- Investigation of mechanisms and susceptibility factors for non-immune-mediated hepatotoxicity for specific compounds
- Characterization of the cellular uptake and toxicity of nanoparticles
As stated above, hepatotoxicity is an important concern during drug development. In the preclinical phase, potential hepatotoxicity can be detected using cell models or in animals. Unfortunately, the mechanisms remain often unclear with this approach. We propose to construct cell models which allow conclusions concerning mechanisms and which can be used as routine tools in early drug development. Concerning nanotoxicology, reliable cell and animal models have to be characterized.