PJ34, a poly-ADP-ribose polymerase inhibitor, modulates visceral mitochondrial activity and CD14 expression following thoracic aortic ischemia-reperfusion.
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.
Stone
David H
DH
Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Albadawi
Hassan
H
Conrad
Mark F
MF
Entabi
Fateh
F
Stoner
Michael C
MC
Casey
Patrick J
PJ
Cambria
Richard P
RP
Watkins
Michael T
MT
D000818:Animals; D001013:Aorta, Thoracic; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury; D013116:Spinal Cord / Q000378:metabolism
D018950:Lipopolysaccharide Receptors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger