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Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes

In order to replace the use of animals in toxicity testing, there is a need to predict human in vivo toxic doses from concentrations that cause adverse effects in in vitro test systems. The virtual cell based assay (VCBA) has been developed to simulate intracellular concentrations as a function of t...

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Detalles Bibliográficos
Autores principales: Worth, Andrew P., Louisse, Jochem, Macko, Peter, Sala Benito, J.V., Paini, Alicia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745147/
https://www.ncbi.nlm.nih.gov/pubmed/28911986
http://dx.doi.org/10.1016/j.tiv.2017.09.009
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author Worth, Andrew P.
Louisse, Jochem
Macko, Peter
Sala Benito, J.V.
Paini, Alicia
author_facet Worth, Andrew P.
Louisse, Jochem
Macko, Peter
Sala Benito, J.V.
Paini, Alicia
author_sort Worth, Andrew P.
collection PubMed
description In order to replace the use of animals in toxicity testing, there is a need to predict human in vivo toxic doses from concentrations that cause adverse effects in in vitro test systems. The virtual cell based assay (VCBA) has been developed to simulate intracellular concentrations as a function of time, and can be used to interpret in vitro concentration-response curves. In this study we refine and extend the VCBA model by including additional target-organ cell models and by simulating the fate and effects of chemicals at the organelle level. In particular, we describe the extension of the original VCBA to simulate chemical fate in liver (HepaRG) cells and cardiomyocytes (ICell cardiomyocytes), and we explore the effects of chemicals at the mitochondrial level. This includes a comparison of: a) in vitro results on cell viability and mitochondrial membrane potential (mmp) from two cell models (HepaRG cells and ICell cardiomyocytes); and b) VCBA simulations, including the cell and mitochondrial compartment, simulating the mmp for both cell types. This proof of concept study illustrates how the relationship between intra cellular, intra mitochondrial concentration, mmp and cell toxicity can be obtained by using the VCBA.
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spelling pubmed-57451472018-01-02 Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes Worth, Andrew P. Louisse, Jochem Macko, Peter Sala Benito, J.V. Paini, Alicia Toxicol In Vitro Article In order to replace the use of animals in toxicity testing, there is a need to predict human in vivo toxic doses from concentrations that cause adverse effects in in vitro test systems. The virtual cell based assay (VCBA) has been developed to simulate intracellular concentrations as a function of time, and can be used to interpret in vitro concentration-response curves. In this study we refine and extend the VCBA model by including additional target-organ cell models and by simulating the fate and effects of chemicals at the organelle level. In particular, we describe the extension of the original VCBA to simulate chemical fate in liver (HepaRG) cells and cardiomyocytes (ICell cardiomyocytes), and we explore the effects of chemicals at the mitochondrial level. This includes a comparison of: a) in vitro results on cell viability and mitochondrial membrane potential (mmp) from two cell models (HepaRG cells and ICell cardiomyocytes); and b) VCBA simulations, including the cell and mitochondrial compartment, simulating the mmp for both cell types. This proof of concept study illustrates how the relationship between intra cellular, intra mitochondrial concentration, mmp and cell toxicity can be obtained by using the VCBA. Pergamon Press 2017-12 /pmc/articles/PMC5745147/ /pubmed/28911986 http://dx.doi.org/10.1016/j.tiv.2017.09.009 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Worth, Andrew P.
Louisse, Jochem
Macko, Peter
Sala Benito, J.V.
Paini, Alicia
Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title_full Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title_fullStr Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title_full_unstemmed Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title_short Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
title_sort virtual cell based assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745147/
https://www.ncbi.nlm.nih.gov/pubmed/28911986
http://dx.doi.org/10.1016/j.tiv.2017.09.009
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