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Liver Cold Storage and Transplantation in the Cold-Adaptive Daurian Ground Squirrels
Published on: July 3, 2025
Preservation solutions alter Mrp2-dependent bile flow in cold ischemic rat livers
Shaoguang Sui1, Atsushi Kudo, Makoto Suematsu
1Department of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
The Journal of Surgical Research
|July 7, 2009
Summary
Adding glycyrrhizin and glutathione to preservation solutions improves bile production and organic anion transport in cold-stored livers by enhancing multidrug resistance-associated protein 2 (Mrp2) function. This supports graft viability without causing cell lysis.
Area of Science:
- Hepatology and Transplant Surgery
- Organ Preservation and Perfusion
- Biomarkers of Graft Dysfunction
Background:
- Cold ischemia impairs liver graft function, specifically decreasing organic anion transport via multidrug resistance-associated protein 2 (Mrp2).
- Previous studies noted Mrp2 dysfunction without significant cell lysis after 8-hour cold storage in University of Wisconsin (UW) solution.
- Graft dysfunction markers in cold-stored livers require investigation across different preservation media.
Purpose of the Study:
- To evaluate bile flow and constituents in cold-ischemic rat livers preserved in UW, ET-Kyoto (ET-K), and histidine-tryptophan-ketoglutarate (HTK) solutions.
- To assess the impact of glycyrrhizin (GL) and glutathione (GSH) on Mrp2 function and bile transport.
- To identify strategies for improving graft viability post-cold ischemia.
Main Methods:
- Rat livers were cold-stored for 8 hours in UW, ET-K, or HTK solutions.
- Bile production and constituents were analyzed post-reperfusion.
- Multidrug resistance-associated protein 2 (Mrp2) transport efficiency was measured using 5-carboxyfluorescein (CF) biliary excretion.
- Intracellular Mrp2 distribution was assessed via immunostaining.
Main Results:
- All preservation solutions led to decreased bile production and biliary glutathione (GSH) levels without cell lysis.
- Biliary excretion of CF, a marker for Mrp2 transport, was significantly delayed in all tested solutions.
- Addition of GL to UW solution, and GL with GSH to ET-K and HTK solutions, improved bile production and CF transport.
- These improvements correlated with enhanced Mrp2 localization to the canalicular membrane.
Conclusions:
- Glycyrrhizin (GL) and glutathione (GSH) significantly enhance bile production and organic anion transport in post-cold ischemic livers.
- The addition of GL and GSH promotes Mrp2 redistribution to the canalicular membrane, restoring transport function.
- These findings suggest a promising strategy for improving liver graft quality and outcomes after cold storage.
