Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion.
The aim of the present study was to investigate the effects of GPI 6150, a new poly(ADP-ribose) polymerase (PARP) inhibitor, in the pathogenesis of splanchnic artery occlusion (SAO) shock. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by reperfusion. At 60 min after reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure, significant increase of tissue myeloperoxidase activity (111 +/- 4.3 U/100 mg wet tissue vs. 28 +/- 3.2 U/100 mg wet tissue of sham-operated rats), and marked histological injury to the distal ileum and a significant mortality (0% survival at 2 h after reperfusion). Immuno-histochemical examination demonstrated a marked increase in the immunoreactivity to PARP, P-selectin, and intercellular adhesion molecule (ICAM-1) in the necrotic ileum. GPI 6150 treatment significantly improved mean arterial blood pressure, prevented the infiltration of neutrophils (72 +/- 3.6 U/100 mg wet tissue) into the reperfused intestine, improved the histological status of the reperfused tissues, markedly reduced the intensity of P-selectin and ICAM-1 in tissue section from SAO-shocked rats, and improved survival. In conclusion, our study demonstrates that GPI 6150 exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock.
Mazzon
Emanuela
E
Department of Biomorphology, School of Medicine, University of Messina, Italy.
Dugo
Laura
L
De
Sarro Angelina
SA
Li
Jia-He
JH
Caputi
Achille P
AP
Zhang
Jie
J
Cuzzocrea
Salvatore
S
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000601:surgery; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects; D015996:Survival Rate
D001578:Benzopyrans; D004791:Enzyme Inhibitors; C417259:GPI 6150; D007546:Isoquinolines; D019007:P-Selectin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase