title: In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice.
abstract: We describe a two-photon microscopy-based method to evaluate the in vivo systemic transport of compounds. This method comprises imaging of the intact liver, kidney and intestine, the main organs responsible for uptake and elimination of xenobiotics and endogenous molecules. The image quality of the acquired movies was sufficient to distinguish subcellular structures like organelles and vesicles. Quantification of the movement of fluorescent dextran and fluorescent cholic acid derivatives in different organs and their sub-compartments over time revealed significant dynamic differences. Calculated half-lives were similar in the capillaries of all investigated organs but differed in the specific sub-compartments, such as parenchymal cells and bile canaliculi of the liver, glomeruli, proximal and distal tubules of the kidney and lymph vessels (lacteals) of the small intestine. Moreover, tools to image immune cells, which can influence transport processes in inflamed tissues, are described. This powerful approach provides new possibilities for the analysis of compound transport in multiple organs and can support physiologically based pharmacokinetic modeling, in order to obtain more precise predictions at the whole body scale.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany. reif@ifado.de.
authors.forename: Raymond
authors.initials: R
authors.lastname: Reif
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany. ghallab@ifado.de.|Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt. ghallab@ifado.de.
authors.forename: Ahmed
authors.identifier: http://orcid.org/0000-0003-0695-3403
authors.initials: A
authors.lastname: Ghallab
authors.affiliation: Centre for Immunology and Infection, University of York, York, UK.|Immunology and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Günther
authors.affiliation: Computational Systems Biology, Bayer Technology Services GmbH, Leverkusen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kuepfer
authors.affiliation: Centre for Immunology and Infection, University of York, York, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany. hengstler@ifado.de.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods*; D014741:Video Recording; D015262:Xenobiotics / Q000032:analysis* / Q000493:pharmacokinetics*
chemical_list: D015262:Xenobiotics; D000082:Acetaminophen
keywords: Bile canaliculi; Drug transport; Glomerulus; Hepatocyte; Intravital imaging; Lacteal; Renal tubules