studies

300A AASLD ABSTRACTS HEPATOLOGY, October, 2015
179
Oxaloacetic Acid Protects the Liver From Warm Ischemia/Reperfusion
Injury
Grégory Merlen, Benoit Lacoste, Benoît Dupont, Valérie-Ann Raymond,
Marc Bilodeau; CRCHUM, Montreal, QC, Canada
Background: Liver ischemia/reperfusion (I/R) is an important
cause of liver damage early after liver transplantation, post
liver resection or during hemorrhagic shock. One of the mechanisms
of cell death occurring in that setting is the disruption of
mitochondrial activity that lead to alterations in cellular energy
metabolism. We hypothesized that oxaloacetic acid (OAA),
which is at the crossroads of gluconeogenesis, amino acid
metabolism and the citric acid cycle, could refuel the energy
metabolism during I/R and therefore protect the liver against
injury. In vitro, we have already demonstrated that OAA was
the most potent citric acid intermediate in its capacity to protect
rat hepatocytes from hypoxia. We have also shown that the
administration of OAA considerably reduces the extent of liver
injury in the left portal vein ligation model of warm liver ischemia
in the rat. We here analyze the potential protective effect
of this compound in a model of hepatic I/R. Methods: Animals
were subjected to 1 hour of left portal pedicle ligation (common
bile duct, left hepatic artery and left portal vein) followed
by reperfusion by unclamping. Animals treated with OAA
[100mg/kg] received a bolus injection through the ileocolic
vein 30 minutes before surgery. The extent of liver I/R injury
was assessed by serum transaminase levels measurements, histological
signs of tissue damage and liver weight (edema).
Results: Treatment with OAA before reperfusion significantly
decreased the AST levels released in blood. After 2 hours of
reperfusion the AST and ALT levels were respectively decreased
by 43%±14% (p