| Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: Application to acetaminophen injury. | |
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MedLine Citation:
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PMID: 22230336 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We have analyzed transcriptomic, proteomic and metabolomic profiles of hepatoma cells cultivated inside a microfluidic biochip with or without acetaminophen (APAP). Without APAP, the results show an adaptive cellular response to the microfluidic environment, leading to the induction of anti-oxidative stress and cytoprotective pathways. In presence of APAP, calcium homeostasis perturbation, lipid peroxidation and cell death are observed. These effects can be attributed to APAP metabolism into its highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). . That toxicity pathway was confirmed by the detection of GSH-APAP, the large production of 2-hydroxybutyrate and 3-hydroxybutyrate, and methionine, cystine, and histidine consumption in the treated biochips. Those metabolites have been reported as specific biomarkers of hepatotoxicity and glutathione depletion in the literature. In addition, the integration of the metabolomic, transcriptomic and proteomic collected profiles allowed a more complete reconstruction of the APAP injury pathways. To our knowledge, this work is the first example of a global integration of microfluidic biochip data in toxicity assessment. Our results demonstrate the potential of that new approach to predictive toxicology. |
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Authors:
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Jean-Matthieu Prot; Andrei Bunescu; Bénédicte Elena-Hermann; Caroline Aninat; Leila Choucha Snouber; Laurent Griscom; Florence Razan; Frederic Bois; Cécile Legallais; Céline Brochot; Anne Corlu; Marc Emmanuel Dumas; Eric Leclerc |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-24 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: - ISSN: 1096-0333 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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CNRS UMR 6600, Laboratoire de Biomécanique et Bio ingénierie, Université de Technologie de Compiègne, Centre de Recherche de Royallieu, BP20529, F-60205, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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