Reif, Raymond, Ghallab, Ahmed, Beattie, Lynette et al. (4 more authors) (2017) In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice. Archives of toxicology. pp. 1335-1352. ISSN 0340-5761
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2016. |
Keywords: | Acetaminophen,Animals,Chemical and Drug Induced Liver Injury,Hepatocytes,Intestines,Kidney,Kupffer Cells,Liver,Male,Mice, Transgenic,Microscopy,Video Recording,Xenobiotics,Journal Article |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 12 Apr 2017 10:40 |
Last Modified: | 26 Nov 2024 00:33 |
Published Version: | https://doi.org/10.1007/s00204-016-1906-5 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1007/s00204-016-1906-5 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115000 |
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Description: In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice