PJ34, a poly-ADP-ribose polymerase inhibitor, modulates visceral mitochondrial activity and CD14 expression following thoracic aortic ischemia-reperfusion.

Abstract

BACKGROUND:

Visceral ischemia-reperfusion injury (VI) contributes to adverse outcomes following the repair of thoracoabdominal aneurysms. Experiments were designed to determine whether a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor modulates indexes of metabolic function (mitochondrial activity), inflammatory cell activation, and tissue inflammation (lipopolysaccharide receptor CD14 messenger ribonucleic acid) following VI.

METHODS:

129S1/SvImj mice were subjected to thoracic aortic occlusion followed by 48 hours of reperfusion. Normal saline was administered to 25 untreated control mice and PJ34 to 21 mice before and immediately after thoracic aortic ischemia-reperfusion. Sham mice (n = 13) underwent median sternotomy alone. At 48 hours, all animals were euthanized and tissues harvested for quantitative analysis.

RESULTS:

PJ34 improved intestinal (P < .05) but not hepatic mitochondrial activity following reperfusion. CD14 messenger ribonucleic acid levels in liver (P < .004), kidney (P < .003), and spinal cord (P < .03) tissue were less in PJ34-treated mice.

CONCLUSIONS:

PJ34 preserved the metabolic function of intestinal but not hepatic tissue during reperfusion. PJ34 uniformly decreased the expression of an important marker of inflammatory cell activation and tissue inflammation in visceral tissue following VI. PARP inhibitors may serve as a therapeutic modality to abrogate the stress response to VI.

• Authors: David H Stone, Hassan Albadawi, Mark F Conrad, Fateh Entabi, Michael C Stoner, Patrick J Casey, Richard P Cambria, Michael T Watkins
• Journal: American journal of surgery (Am J Surg) Vol. 198 Issue 2 Pg. 250-5 (Aug 2009) ISSN: 1879-1883 [Electronic] United States
• PMID: 19268911 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharide Receptors
• N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
• Phenanthrenes
• Poly(ADP-ribose) Polymerase Inhibitors
• RNA, Messenger

Topics

• Animals
• Aorta, Thoracic
• Intestinal Mucosa (metabolism)
• Kidney (metabolism)
• Lipopolysaccharide Receptors (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mitochondria (drug effects, metabolism)
• Phenanthrenes (pharmacology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Polymerase Chain Reaction
• RNA, Messenger (metabolism)
• Reperfusion Injury
• Spinal Cord (metabolism)