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 language | English |
|---|---|
| Pages (from-to) | 894-901 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 44 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2006 |
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Keywords
- BCECF
- Confocal microscopy
- Hepatocytes
- Lactate dehydrogenase
- Mannitol
- Monensin
- Osmotic stress
- pH
- Sinusoidal cells
ASJC Scopus subject areas
- Gastroenterology
Cite this
Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers. / Vairetti, Mariapia; Richelmi, Plinio; Bertè, Francantonio; Currin, Robert T.; Lemasters, John J.; Imberti, Roberto.
In: Journal of Hepatology, Vol. 44, No. 5, 05.2006, p. 894-901.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers
AU - Vairetti, Mariapia
AU - Richelmi, Plinio
AU - Bertè, Francantonio
AU - Currin, Robert T.
AU - Lemasters, John J.
AU - Imberti, Roberto
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - BCECF
KW - Confocal microscopy
KW - Hepatocytes
KW - Lactate dehydrogenase
KW - Mannitol
KW - Monensin
KW - Osmotic stress
KW - pH
KW - Sinusoidal cells
UR - http://www.scopus.com/inward/record.url?scp=33645758042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645758042&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2005.08.007
DO - 10.1016/j.jhep.2005.08.007
M3 - Article
VL - 44
SP - 894
EP - 901
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 5
ER -