作者
Patricio Godoy, Nicola J Hewitt, Ute Albrecht, Melvin E Andersen, Nariman Ansari, Sudin Bhattacharya, Johannes Georg Bode, Jennifer Bolleyn, Christoph Borner, Jan Boettger, Albert Braeuning, Robert A Budinsky, Britta Burkhardt, Neil R Cameron, Giovanni Camussi, Chong-Su Cho, Yun-Jaie Choi, J Craig Rowlands, Uta Dahmen, Georg Damm, Olaf Dirsch, María Teresa Donato, Jian Dong, Steven Dooley, Dirk Drasdo, Rowena Eakins, Karine Sa Ferreira, Valentina Fonsato, Joanna Fraczek, Rolf Gebhardt, Andrew Gibson, Matthias Glanemann, Chris EP Goldring, María José Gómez-Lechón, Geny MM Groothuis, Lena Gustavsson, Christelle Guyot, David Hallifax, Seddik Hammad, Adam Hayward, Dieter Haeussinger, Claus Hellerbrand, Philip Hewitt, Stefan Hoehme, Hermann-Georg Holzhuetter, J Brian Houston, Jens Hrach, Kiyomi Ito, Hartmut Jaeschke, Verena Keitel, Jens M Kelm, B Kevin Park, Claus Kordes, Gerd A Kullak-Ublick, Edward L LeCluyse, Peng Lu, Jennifer Luebke-Wheeler, Anna Lutz, Daniel J Maltman, Madlen Matz-Soja, Patrick McMullen, Irmgard Merfort, Simon Messner, Christoph Meyer, Jessica Mwinyi, Dean J Naisbitt, Andreas K Nussler, Peter Olinga, Francesco Pampaloni, Jingbo Pi, Linda Pluta, Stefan A Przyborski, Anup Ramachandran, Vera Rogiers, Cliff Rowe, Celine Schelcher, Kathrin Schmich, Michael Schwarz, Bijay Singh, Ernst HK Stelzer, Bruno Stieger, Regina Stoeber, Yuichi Sugiyama, Ciro Tetta, Wolfgang E Thasler, Tamara Vanhaecke, Mathieu Vinken, Thomas S Weiss, Agata Widera, Courtney G Woods, Jinghai James Xu, Kathy M Yarborough, Jan G Hengstler
发表日期
2013/8
来源
Archives of toxicology
卷号
87
页码范围
1315-1530
出版商
Springer Berlin Heidelberg
简介
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro …
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P Godoy, NJ Hewitt, U Albrecht, ME Andersen… - Archives of toxicology, 2013