Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers-Reference-Cited by-同舟云学术

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers

Published:2024-09-01 Issue:3 Volume:327 Page:G424-G437
ISSN:0193-1857
Container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology
language:en
Short-container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology

Author:

Monti Christopher E.¹²,Hong Seung-Keun³,Audi Said H.¹⁴^ORCID,Lee Whayoung⁵,Joshi Amit¹,Terhune Scott S.²,Kim Joohyun³^ORCID,Dash Ranjan K.¹⁴⁶^ORCID

Affiliation:

1. Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

2. Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

3. Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

4. Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States

5. Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

6. Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Abstract

We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpgi.00048.2024

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