English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

During liver transplantation, ischemia-reperfusion injury (IRI) is inevitableand decreases the overall success of the surgery. While guidelines exist, thereis no reliable way to quantitatively assess the degree of IRI present in theliver. Our recent study has shown a correlation between the bile-to-plasmaratio of FDA-approved sodium fluorescein (SF) and the degree of hepatic IRI,presumably due to IRI-induced decrease in the activity of the hepatic multidrugresistance-associated protein 2 (MRP2); however, the contribution of SF bloodclearance via the bile is still convoluted with other factors, such as renalclearance. In this work, we sought to computationally model SF blood clearancevia the bile. First, we converted extant SF fluorescence data from rat wholeblood, plasma, and bile to concentrations using calibration curves. Next, basedon these SF concentration data, we generated a liver-centric,physiologically-based pharmacokinetic (PBPK) model of SF liver uptake andclearance via the bile. Model simulations show that SF bile concentration ishighly sensitive to a change in the activity of hepatic MPR2. These simulationssuggest that SF bile clearance along with the PBPK model can be used toquantify the effect of IRI on the activity of MRP2.

Physiologically-Based Pharmacokinetic Modeling of Blood Clearance of  Liver Fluorescent Markers for the Assessment of the Degree of Hepatic  Ischemia-Reperfusion Injury