Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers

Mariapia Vairetti, Plinio Richelmi, Francantonio Bertè, Robert T. Currin, John J. Lemasters, Roberto Imberti

Research output: Contribution to journalArticle

Abstract

Background/Aims: The purpose of the present study was to characterize the role of Na+, pH and cellular swelling in the pathogenesis of hypoxic injury to rat livers. Methods and Results: When livers were perfused with hypoxic Krebs-Henseleit bicarbonate buffer (KHB) containing 143 mM Na+, release of LDH began after 30 min and was maximal after 60 min. In livers perfused with choline-substituted low-Na+ KHB (25 mM Na+), LDH release began after 60 min and peaked after 120 min or longer. Supplementation of KHB with mannitol, a permeant sugar with antioxidant properties, suppressed LDH release, whereas sucrose, an impermeant disaccharide, did not afford protection. At the end of hypoxic perfusions with KHB and low-Na+ KHB, liver weight was not different, whereas mannitol but not sucrose increased liver weight after hypoxia. At pH 7.4, monensin, a Na+-H+ ionophore, reversed protection against hypoxia by low-Na+ KHB (10 mM Na+) but had no effect at pH 6.8. As measured directly by confocal microscopy of biscarboxyethylcarboxyfluorescein fluorescence, pH was lower during perfusion with low-Na+ KHB than KHB. Conclusions: Cytoprotection by low Na+ was not mediated by prevention of Na+-dependent tissue swelling. Rather, promotion of intracellular acidification likely mediates cytoprotection in low-Na+ buffer.

Original languageEnglish
Pages (from-to)894-901
Number of pages8
JournalJournal of Hepatology
Volume44
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • BCECF
  • Confocal microscopy
  • Hepatocytes
  • Lactate dehydrogenase
  • Mannitol
  • Monensin
  • Osmotic stress
  • pH
  • Sinusoidal cells

ASJC Scopus subject areas

  • Gastroenterology

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