ISSN: 2161-0495
+44 1478 350008
Jos C S Kleinjans
England
Research Article
In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein
Expression Profiles
Author(s): Freek G Bouwman, Anke Van Summeren, Anne Kienhuis, Leo van der Ven, Ewoud N Speksnijder, Jean-Paul Noben, Johan Renes, Jos C S Kleinjans and Edwin C M Mariman
Freek G Bouwman, Anke Van Summeren, Anne Kienhuis, Leo van der Ven, Ewoud N Speksnijder, Jean-Paul Noben, Johan Renes, Jos C S Kleinjans and Edwin C M Mariman
To reduce the amount of laboratory animals which are used to analyze hepatotoxic properties of chemicals and drugs, the development of alternative in vitro models is necessary. Ideally these in vitro models reflect the in vivo toxicological response and cholestasis. In this study the protein expression in livers from C57BL/6 mice after cyclosporin A-induced cholestasis was analyzed. After 25 days of a daily cyclosporine A treatment the cholestatic phenotype was established. An in vitro to this in vivo study comparison was made by using the results of our previous studies with HepG2 and primary mouse hepatocytes. The in vivo proteomics data show cyclosporin Ainduced oxidative stress and mitochondrial dysfunction was actually induced, leading to a decreased mitochondrial ATP production and an altered urea cycle. These processes were also altered by cyclosporin A in the in vitro models H.. View More»
DOI:
10.4172/2161-0495.1000299