Antioxidant and prooxidant properties of ascorbic acid on hepatic dysfunction induced by cold ischemia/reperfusion

Eur J Pharmacol. 2008 Feb 12;580(3):401-6. doi: 10.1016/j.ejphar.2007.11.023. Epub 2007 Nov 23.


Oxidative stress, which has been generated during reperfusion after a liver transplant, has been implicated in the higher rates of postoperative organ dysfunction. The aim of this study was to examine the effect of ascorbic acid on reperfusion injury after hepatic cold preservation. Isolated perfused rat livers were preserved in a University of Wisconsin solution for 30 h at 4 degrees C. The bile output was significantly lower after cold ischemia/reperfusion. In contrast, the portal pressure, lactate dehydrogenase and purine nucleoside phosphorylase activities were elevated by cold ischemia/reperfusion. These changes were attenuated at ascorbic acid concentrations of 0.25 and 0.5 mM. However, they were augmented at a concentration of 2 mM. Cold ischemia/reperfusion decreased the reduced to oxidized glutathione ratio, whereas it increased the level of lipid peroxidation and mitochondrial swelling. These changes were prevented exposing the liver to 0.5 mM ascorbic acid but were augmented at 2 mM ascorbic acid. These results suggest that cold ischemia/reperfusion injury is associated with a higher level of oxidative stress and ascorbic acid may act not only as an antioxidant but also as a prooxidant during cold ischemia/reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Bile / metabolism
  • Cold Ischemia / adverse effects
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / physiopathology
  • Male
  • Malondialdehyde / metabolism
  • Mitochondrial Swelling / drug effects
  • Models, Animal
  • Oxidants / pharmacology*
  • Portal Pressure / drug effects
  • Purine-Nucleoside Phosphorylase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology
  • Reperfusion Injury / physiopathology*
  • Time Factors


  • Antioxidants
  • Oxidants
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Purine-Nucleoside Phosphorylase
  • Glutathione
  • Ascorbic Acid
  • Glutathione Disulfide