SEURAT-1 liver gold reference compounds: a mechanism-based review
| العنوان: | SEURAT-1 liver gold reference compounds: a mechanism-based review |
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| المؤلفون: | David Bower, Jeffrey S. Wiseman, Michael Schwarz, Brigitte Landesmann, Martin O. Leonard, Marina Goumenou, Silvia Maggioni, Paul Jennings |
| المصدر: | Archives of Toxicology. 88:2099-2133 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Phospholipidosis, Alternative methods, Health, Toxicology and Mutagenesis, Drug Evaluation, Preclinical, Mechanism based, General Medicine, Computational biology, In Vitro Techniques, Reference Standards, Biology, Pharmacology, Animal Testing Alternatives, Toxicology, medicine.disease, Human situation, Cell Line, Liver, Animal Testing Alternative, medicine, Animals, Humans, Steatosis, Animal testing, Mode of action |
| الوصف: | 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 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 specific 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. |
| تدمد: | 1432-0738 0340-5761 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f53d18cda20f60b18f589f0fa2ac649e https://doi.org/10.1007/s00204-014-1410-8 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....f53d18cda20f60b18f589f0fa2ac649e |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320738 03405761 |
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