alexa In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein Expression Profiles
ISSN: 2161-0495

Journal of Clinical Toxicology
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Research Article

In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein Expression Profiles

Freek G Bouwman1#, Anke Van Summeren1,2#, Anne Kienhuis3, Leo van der Ven3, Ewoud N Speksnijder4, Jean-Paul Noben5, Johan Renes1, Jos C S Kleinjans2 and Edwin C M Mariman1*

1Department of Human Biology, Maastricht University, P.O. box 616, 6200 MD Maastricht, The Netherlands

2Department of Toxicogenomics, Maastricht University, P.O. box 616, 6200 MD Maastricht, The Netherlands

3Laboratory for Health Protection Research, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands

4Department of Toxicogenetics, Leiden University Medical Center, 2300 RC, Leiden, the Netherlands

5Hasselt University, Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium

#Both authors contributed equally to this manuscript

*Corresponding Author:
Dr. Edwin C. M. Mariman
Department of Human Biology, Maastricht University
P.O. box 616, 6200 MD Maastricht, The Netherlands
Tel: +31 (0) 43 38
Fax: +31 (0) 43 3670976
E-mail: [email protected]

Received Date April 07, 2016; Accepted Date May 12, 2016; Published Date May 19, 2016

Citation: Bouwman FG, Summeren AV, Kienhuis A, Ven LVD, Speksnijder EN et al. (2016) In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein Expression Profiles. J Clin Toxicol 6:299. doi: 10.4172/2161-0495.1000299

Copyright: © 2016 Bouwman FG, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 HepG2 and primary mouse hepatocytes. In addition, detoxification enzymes like methyl- and glutathione-Stransferases were differentially expressed after cyclosporin A treatment. Changes in these detoxification enzymes were mainly detected in vivo, though primary mouse hepatocytes show a differential expression of some of these enzymes. By means of a functional classification of differentially expressed proteins we demonstrated similarities and differences between in vitro and in vivo models in the proteome response of cyclosporin A-induced hepatotoxicity.


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