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2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake.
- Source :
-
American Journal of Physiology: Gastrointestinal & Liver Physiology . Sep2007, Vol. 293, pG623-G630. 8p. 1 Chart, 5 Graphs. - Publication Year :
- 2007
-
Abstract
- Ischemia-reperfusion (l/R) injury is a commonly encountered clinical problem in liver surgery and transplantation. The pathogenesis of I/R injury is multifactorial, but mitochondrial Ca2+ overload plays a central role. We have previously defined a novel pathway for mitochondrial Ca2+ handling and now further characterize this pathway and investigate a novel Ca2+-channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB), for preventing hepatic I/R injury. The effect of 2-APB on cellular and mitochondrial Ca2+ uptake was evaluated in vitro by using 45Ca2+. Subsequently, 2-APB (2 mg/kg) or vehicle was injected into the portal vein of anesthetized rats either before or following 1 h of inflow occlusion to 70% of the liver. After 3 h of reperfusion, liver injury was assessed enzymatically and histologically. Hep O2 cells transfected with green fluorescent protein-tagged cytochrome c were used to evaluate mitochondrial permeability. 2-APB dose-dependently blocked Ca2+ uptake in isolated liver mitochondria and reduced cellular Ca2+ accumulation in Hep G2 cells. In vivo I/R increased liver enzymes 10-fold, and 2-APB prevented this when administered pre- or postischemia. 2-APB significantly reduced cellular damage determined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of liver tissue. In vitro I/R caused a dissociation between cytochrome c and mitochondria in Hep G2 cells that was prevented by administration of 2-APB. These data further establish the role of cellular Ca2+ uptake and subsequent mitochondrial Ca2+ overload in I/R injury and identify 2-APB as a novel pharmacological inhibitor of liver I/R injury even when administered following a prolonged ischemic insult. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ISCHEMIA
*CALCIUM
*LIVER surgery
*MITOCHONDRIA
*PROTOPLASM
*CYTOCHROMES
*CELLS
Subjects
Details
- Language :
- English
- ISSN :
- 01931857
- Volume :
- 293
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Gastrointestinal & Liver Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 26640752
- Full Text :
- https://doi.org/10.1152/ajpgi.00521.2006