%0 Journal Article %1 Worth2017 %A Worth, Andrew P. %A Louisse, Jochem %A Macko, Peter %A Sala Benito, Jose Vicente %A Paini, Alicia %D 2017 %J Toxicology in Vitro %K HepaRG ICell_cardiomyocyte In_silico In_vitro Mitochondrial_membrane_potential VCBA %R 10.1016/j.tiv.2017.09.009 %T Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes %X 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.

@article{Worth2017, abstract = {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.}, added-at = {2019-06-17T23:34:05.000+0200}, author = {Worth, Andrew P. and Louisse, Jochem and Macko, Peter and {Sala Benito}, Jose Vicente and Paini, Alicia}, biburl = {https://www.bibsonomy.org/bibtex/2928f3e66c404732cb1131e45eb2254e9/fcdi}, doi = {10.1016/j.tiv.2017.09.009}, interhash = {021b2f0f84664d02d15e9c98b1e0b5b3}, intrahash = {928f3e66c404732cb1131e45eb2254e9}, issn = {18793177}, journal = {Toxicology in Vitro}, keywords = {HepaRG ICell_cardiomyocyte In_silico In_vitro Mitochondrial_membrane_potential VCBA}, timestamp = {2019-06-18T22:58:44.000+0200}, title = {{Virtual Cell Based Assay simulations of intra-mitochondrial concentrations in hepatocytes and cardiomyocytes}}, year = 2017 }