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Arch Toxicol (2014) 88:20992133 DOI 10.1007/s00204-014-1410-8
REVIEW ARTICLE
SEURAT1 liver gold reference compounds: a mechanismbased review
Paul Jennings Michael Schwarz Brigitte Landesmann Silvia Maggioni Marina Goumenou David Bower Martin O. Leonard Jeffrey S. Wiseman
Received: 12 September 2014 / Accepted: 1 October 2014 / Published online: 14 November 2014 Springer-Verlag Berlin Heidelberg 2014
are considered under the category of lipid dysregulation.
We focused on four compound classes capable of initiating such events, i.e., chemically reactive compounds, compounds with specic cellular targets, compounds that modulate lipid regulatory networks, and compounds that disrupt the plasma membrane. We describe the molecular mechanisms of these compounds and the cellular response networks which they elicit. This information will be helpful to both improve our understanding of mode of action and help in the selection of appropriate mechanistic biomarkers, allowing us to progress the development of animal-free models with improved predictivity to the human situation.
Keywords SEURAT-1 Hepatotoxin MIE MoA
Nuclear receptor Stress response
Abstract There is an urgent need for the development of alternative methods to replace animal testing for the prediction of repeat dose chemical toxicity. To address this need, the European Commission and Cosmetics Europe have jointly funded a research program for Safety Evaluation Ultimately Replacing Animal Testing. The goal of this program was the development of in vitro cellular systems and associated computational capabilities for the prediction of hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. An essential component of this effort is the choice of appropriate reference compounds that can be used in the development and validation of assays. In this review, we focus on the selection of reference compounds for liver pathologies in the broad categories of cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and apoptosis are considered under the category of cytotoxicity, while steatosis, cholestasis, and phospholipidosis
P. Jennings
Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck, 6020 Innsbruck, Austria
M. Schwarz
Institute of Experimental and Clinical Pharmacologyand Toxicology, Department of Toxicology, Universityof Tuebingen, Wilhelmstr. 56, 72074 Tuebingen, Germany
B. Landesmann
Systems Toxicology Unit and the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Ispra, Italy
S. Maggioni
Department of Environmental Health Sciences, Istituto di...