Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models

Xiao Fu, James P. Sluka, Sherry G. Clendenon, Kenneth Dunn, Zemin Wang, James E. Klaunig, James A. Glazier

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0198060
JournalPLoS One
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Xenobiotics
xenobiotics
Metabolism
Liver
liver
metabolism
blood flow
Blood
liver function
pipes
blood vessels
transporters
Blood Vessels
Linear Models
Pipe
prediction
dosage

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Fu, X., Sluka, J. P., Clendenon, S. G., Dunn, K., Wang, Z., Klaunig, J. E., & Glazier, J. A. (2018). Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. PLoS One, 13(9), [e0198060]. https://doi.org/10.1371/journal.pone.0198060

Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. / Fu, Xiao; Sluka, James P.; Clendenon, Sherry G.; Dunn, Kenneth; Wang, Zemin; Klaunig, James E.; Glazier, James A.

In: PLoS One, Vol. 13, No. 9, e0198060, 01.09.2018.

Research output: Contribution to journalArticle

Fu, X, Sluka, JP, Clendenon, SG, Dunn, K, Wang, Z, Klaunig, JE & Glazier, JA 2018, 'Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models', PLoS One, vol. 13, no. 9, e0198060. https://doi.org/10.1371/journal.pone.0198060
Fu, Xiao ; Sluka, James P. ; Clendenon, Sherry G. ; Dunn, Kenneth ; Wang, Zemin ; Klaunig, James E. ; Glazier, James A. / Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models. In: PLoS One. 2018 ; Vol. 13, No. 9.
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