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    In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice

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    Author
    Reif, R; Ghallab, A; Beattie, L; Guenther, G; Kuepfer, L; Kaye, PM; Hengstler, JG
    Date
    2017-03-01
    Source Title
    Archives of Toxicology
    Publisher
    SPRINGER HEIDELBERG
    University of Melbourne Author/s
    Beattie, Lynette
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Reif, R., Ghallab, A., Beattie, L., Guenther, G., Kuepfer, L., Kaye, P. M. & Hengstler, J. G. (2017). In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice. ARCHIVES OF TOXICOLOGY, 91 (3), pp.1335-1352. https://doi.org/10.1007/s00204-016-1906-5.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255849
    DOI
    10.1007/s00204-016-1906-5
    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.

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