The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2002-2003

Development of an In Vitro System to Test the Effects and Toxicity of Anti-Inflammatory and Anti-Fibrotic Drugs in the Human Liver

Geny Groothuis, PhD
University of Groningen, Groningen, The Netherlands

Liver cirrhosis is a fatal liver disease and belongs to the top ten causes of death in the Western World. Cirrhosis is characterized by, among others, excessive deposition of connective tissue (fibrosis) leading to loss of liver function. To date, no adequate drug therapy is available due to the fact that the potential drugs show either lack of effect or serious side effects. The only effective treatment is liver transplantation.

In addition the pathogenesis of the disease process, being the onset and progression of fibrosis and its reversibility, are only partially understood. Research concerning the pathogenesis and the development of drugs is usually performed in animal experiments, which is accompanied by relatively high discomfort for the animals.

In this project an in vitro system using liver slices will be developed in order to be able to investigate the pathogenesis of the disease without treatment of the animals, thereby reducing the number and the discomfort of the animals used. Moreover, the system will allow us to test drugs, developed in our institute for efficacy and toxicity in vitro and in vivo, as is currently the case. In addition, such an in vitro system can be applied to human liver tissue, enabling us to study human specific features of the pathogenesis of liver fibrosis and cirrhosis. This will contribute to a safer first administration of newly developed drugs in man and to a reduction, replacement and refinement of animal experiments.