Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers

Shaoguang Sui, Atsushi Kudo, Makoto Suematsu, Shinji Tanaka, Noriaki Nakamura, Koji Ito, Shigeki Arii

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Previously, decreased organic anion transport through multidrug resistance protein 2 (Mrp2) was observed without any notable cell lysis, even when the livers were stored for 8 hours in University of Wisconsin solution (UW). The aim of this study was to examine the bile flow and its constituents, markers of graft dysfunction without necrosis in cold ischemic livers, using the following preservation media: UW, ET-Kyoto solution (ET-K) and histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Rat livers were stored at 4°C for 8 hours in the preservation media, and reperfused to collect the bile and determine their constituents. Glycyrrhizin (GL) and/or glutathione (GSH) were added to the media as necessary. The transport efficiency of Mrp2 was assessed by the biliary excretion of 5-carboxyfluorescein (CF), a fluoroprobe excreted from Mrp2. The Intracellular distribution of Mrp2 was determined by immunostaining. Results: Livers stored for 8 hours exhibited significantly decreased bile production and biliary glutathione (GSH) levels without notable cell lysis. CF excretion was significantly delayed in all solutions. However, these markers were remarkably improved by the redistribution of Mrp2 from the cytoplasm to the canalicular membrane, when the livers were exposed to UW in the presence of GL. Moreover, livers exposed to the Kyoto and HTK solutions increased their bile production and organic anion transport in the presence of GL and GSH. Conclusion: These results suggest that the addition of GL and GSH to preservation solutions improves bile production and biliary organic anion transport by increasing Mrp2 localization to the bile canaliculi in post-cold ischemic livers. (248 words).

Original languageEnglish
Pages (from-to)572-581
Number of pages10
JournalJournal of Surgical Research
Volume159
Issue number1
DOIs
Publication statusPublished - 2010 Mar

Fingerprint

Bile
Glycyrrhizic Acid
Liver
Anions
Glutathione
Bile Canaliculi
P-glycoprotein 2
Cytoplasm
Necrosis
Transplants
Membranes

Keywords

  • cold ischemia-reperfusion injury
  • ET-Kyoto solution
  • histidine-tryptophan-ketoglutarate solution
  • Mrp2, liver function
  • University of Wisconsin solution

ASJC Scopus subject areas

  • Surgery

Cite this

Sui, S., Kudo, A., Suematsu, M., Tanaka, S., Nakamura, N., Ito, K., & Arii, S. (2010). Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers. Journal of Surgical Research, 159(1), 572-581. https://doi.org/10.1016/j.jss.2008.12.043

Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers. / Sui, Shaoguang; Kudo, Atsushi; Suematsu, Makoto; Tanaka, Shinji; Nakamura, Noriaki; Ito, Koji; Arii, Shigeki.

In: Journal of Surgical Research, Vol. 159, No. 1, 03.2010, p. 572-581.

Research output: Contribution to journalArticle

Sui, S, Kudo, A, Suematsu, M, Tanaka, S, Nakamura, N, Ito, K & Arii, S 2010, 'Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers', Journal of Surgical Research, vol. 159, no. 1, pp. 572-581. https://doi.org/10.1016/j.jss.2008.12.043
Sui, Shaoguang ; Kudo, Atsushi ; Suematsu, Makoto ; Tanaka, Shinji ; Nakamura, Noriaki ; Ito, Koji ; Arii, Shigeki. / Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers. In: Journal of Surgical Research. 2010 ; Vol. 159, No. 1. pp. 572-581.
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abstract = "Background: Previously, decreased organic anion transport through multidrug resistance protein 2 (Mrp2) was observed without any notable cell lysis, even when the livers were stored for 8 hours in University of Wisconsin solution (UW). The aim of this study was to examine the bile flow and its constituents, markers of graft dysfunction without necrosis in cold ischemic livers, using the following preservation media: UW, ET-Kyoto solution (ET-K) and histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Rat livers were stored at 4°C for 8 hours in the preservation media, and reperfused to collect the bile and determine their constituents. Glycyrrhizin (GL) and/or glutathione (GSH) were added to the media as necessary. The transport efficiency of Mrp2 was assessed by the biliary excretion of 5-carboxyfluorescein (CF), a fluoroprobe excreted from Mrp2. The Intracellular distribution of Mrp2 was determined by immunostaining. Results: Livers stored for 8 hours exhibited significantly decreased bile production and biliary glutathione (GSH) levels without notable cell lysis. CF excretion was significantly delayed in all solutions. However, these markers were remarkably improved by the redistribution of Mrp2 from the cytoplasm to the canalicular membrane, when the livers were exposed to UW in the presence of GL. Moreover, livers exposed to the Kyoto and HTK solutions increased their bile production and organic anion transport in the presence of GL and GSH. Conclusion: These results suggest that the addition of GL and GSH to preservation solutions improves bile production and biliary organic anion transport by increasing Mrp2 localization to the bile canaliculi in post-cold ischemic livers. (248 words).",
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