Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

Thorling, Camilla A., Liu, Xin, Burczynski, Frank J., Fletcher, Linda M., Roberts, Michael S. and Sanchez, Washington Y. (2013) Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury. Journal of Biomedical Optics, 18 10: 1-12. doi:10.1117/1.JBO.18.10.101306

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Author Thorling, Camilla A.
Liu, Xin
Burczynski, Frank J.
Fletcher, Linda M.
Roberts, Michael S.
Sanchez, Washington Y.
Title Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury
Journal name Journal of Biomedical Optics   Check publisher's open access policy
ISSN 1083-3668
1560-2281
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1117/1.JBO.18.10.101306
Open Access Status File (Publisher version)
Volume 18
Issue 10
Start page 1
End page 12
Total pages 12
Place of publication Bellingham, WA United States
Publisher S P I E - International Society for Optical Engineering
Collection year 2014
Language eng
Abstract The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein.
Keyword Multiphoton Microscopy
Intravital imaging
Ischemia reperfusion injury
Biliary excretion
Drug transport
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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