Oxidative stress and matrix metalloproteinase-9 activity in the liver after hypoxia and reoxygenation with 21% or 100% oxygen in newborn piglets.

Abstract

We designed a randomized controlled study to identify and compare the liver tissue responses in systemic hypoxia and resuscitation with 21% and 100% oxygen using an animal model of neonatal hypoxia and reoxygenation. Twenty-seven piglets (1-3 days old, weight 1.5-2.0 kg) were acutely instrumented and mechanically ventilated. The animals underwent 2 h of normocapnic alveolar hypoxia (10-15% oxygen) then reoxygenation with 21% or 100% oxygen for 1 h, then 1 h with 21% oxygen. Controls were sham-operated without hypoxia-reoxygenation. After 2 h of reoxygenation liver tissue samples were immediately processed for histological and biochemical analyses of markers of oxidative stress and tissue injury. Two hours of hypoxia caused a significant reduction in mean arterial pressure with cardiogenic shock and metabolic acidemia, with similar recovery upon resuscitation with 21% and 100% oxygen. After 2 h of reoxygenation, the hepatic GSSG:total glutathione ratio and matrix metalloproteninase-9 activity, which correlated with the portal venous oxygenation at 15 min of reoxygenation, were greater in the 100% group and hepatic lactate level was higher in the 21% group than the controls (all P<0.05). Both hypoxic-reoxygenated groups had similarly elevated hepatic Bcl-2 levels. Apart from more non-distinct mitochondria identified in the 100% group, hepatic tissue adenylate energy charge and plasma transaminases levels did not differ among groups. We concluded that in this acute model of neonatal hypoxia and reoxygenation, resuscitation using 21% oxygen avoids the excess oxidative stress and elevated matrix metalloproteninase-9 activity in the liver when 100% oxygen was used. The study supports the conservative use of oxygen in optimizing post-hypoxic hepatic recovery.

• Authors: Jonathan P Stevens, Thomas Churchill, Karien Fokkelman, Erika Haase, Halliday Idikio, Gregory Korbutt, David L Bigam, Po-Yin Cheung
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 580 Issue 3 Pg. 385-93 (Feb 12 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18154950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Lactic Acid
• Adenosine Monophosphate
• Adenosine Diphosphate
• Adenosine Triphosphate
• Aspartate Aminotransferases
• Alanine Transaminase
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Glutathione
• Oxygen
• Glutathione Disulfide

Topics

• Adenosine Diphosphate (metabolism)
• Adenosine Monophosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Alanine Transaminase (blood)
• Animals
• Animals, Newborn
• Aspartate Aminotransferases (blood)
• Female
• Glutathione (metabolism)
• Glutathione Disulfide (metabolism)
• Hypoxia (blood, physiopathology)
• Lactic Acid (metabolism)
• Liver (drug effects, metabolism, pathology)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Oxidative Stress (drug effects)
• Oxygen (blood, pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Random Allocation
• Swine
• Time Factors
• bcl-2-Associated X Protein (metabolism)