Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models.
Computational models of normal liver function and xenobiotic induced liver damage are increasingly being used to interpret in vitro and in vivo data and as an approach to the de novo prediction of the liver's response to xenobiotics. The microdosimetry (dose at the level of individual cells) of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6136710?pdf=render |
| _version_ | 1818175137534443520 |
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| author | Xiao Fu James P Sluka Sherry G Clendenon Kenneth W Dunn Zemin Wang James E Klaunig James A Glazier |
| author_facet | Xiao Fu James P Sluka Sherry G Clendenon Kenneth W Dunn Zemin Wang James E Klaunig James A Glazier |
| author_sort | Xiao Fu |
| collection | DOAJ |
| description | Computational models of normal liver function and xenobiotic induced liver damage are increasingly being used to interpret in vitro and in vivo data and as an approach to the de novo prediction of the liver's response to xenobiotics. The microdosimetry (dose at the level of individual cells) of xenobiotics vary spatially within the liver because of both compound-independent and compound-dependent factors. In this paper, we build model liver lobules to investigate the interplay between vascular structure, blood flow and cellular transport that lead to regional variations in microdosimetry. We then compared simulation results obtained using this complex spatial model with a simpler linear pipe model of a sinusoid and a very simple single box model. We found that variations in diffusive transport, transporter-mediated transport and metabolism, coupled with complex liver sinusoid architecture and blood flow distribution, led to three essential patterns of xenobiotic exposure within the virtual liver lobule: (1) lobular-wise uniform, (2) radially varying and (3) both radially and azimuthally varying. We propose to use these essential patterns of exposure as a reference for selection of model representations when a computational study involves modeling detailed hepatic responses to xenobiotics. |
| first_indexed | 2024-12-11T19:55:31Z |
| format | Article |
| id | doaj.art-77faf0bce05e48aab4de960dd826f832 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T19:55:31Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-77faf0bce05e48aab4de960dd826f8322022-12-22T00:52:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e019806010.1371/journal.pone.0198060Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models.Xiao FuJames P SlukaSherry G ClendenonKenneth W DunnZemin WangJames E KlaunigJames A GlazierComputational models of normal liver function and xenobiotic induced liver damage are increasingly being used to interpret in vitro and in vivo data and as an approach to the de novo prediction of the liver's response to xenobiotics. The microdosimetry (dose at the level of individual cells) of xenobiotics vary spatially within the liver because of both compound-independent and compound-dependent factors. In this paper, we build model liver lobules to investigate the interplay between vascular structure, blood flow and cellular transport that lead to regional variations in microdosimetry. We then compared simulation results obtained using this complex spatial model with a simpler linear pipe model of a sinusoid and a very simple single box model. We found that variations in diffusive transport, transporter-mediated transport and metabolism, coupled with complex liver sinusoid architecture and blood flow distribution, led to three essential patterns of xenobiotic exposure within the virtual liver lobule: (1) lobular-wise uniform, (2) radially varying and (3) both radially and azimuthally varying. We propose to use these essential patterns of exposure as a reference for selection of model representations when a computational study involves modeling detailed hepatic responses to xenobiotics.http://europepmc.org/articles/PMC6136710?pdf=render |
| spellingShingle | Xiao Fu James P Sluka Sherry G Clendenon Kenneth W Dunn Zemin Wang James E Klaunig James A Glazier Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. PLoS ONE |
| title | Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. |
| title_full | Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. |
| title_fullStr | Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. |
| title_full_unstemmed | Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. |
| title_short | Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. |
| title_sort | modeling of xenobiotic transport and metabolism in virtual hepatic lobule models |
| url | http://europepmc.org/articles/PMC6136710?pdf=render |
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