Abstract
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), Immunohistochemical 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 222-227 |
| Number of pages | 6 |
| Journal | Shock |
| Volume | 17 |
| Issue number | 3 |
| State | Published - Mar 2002 |
| Externally published | Yes |
Fingerprint
Keywords
- Neutrophil infiltration
- Nitric oxide
- Shock
ASJC Scopus subject areas
- Physiology
- Critical Care and Intensive Care Medicine
Cite this
Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion. / Mazzon, Emanuela; Dugo, Laura; De Sarro, Angelina; Li, Jia He; Caputi, Achille P.; Zhang, Jie; Cuzzocrea, Salvatore.
In: Shock, Vol. 17, No. 3, 03.2002, p. 222-227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion
AU - Mazzon, Emanuela
AU - Dugo, Laura
AU - De Sarro, Angelina
AU - Li, Jia He
AU - Caputi, Achille P.
AU - Zhang, Jie
AU - Cuzzocrea, Salvatore
PY - 2002/3
Y1 - 2002/3
N2 - 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), Immunohistochemical 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.
AB - 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), Immunohistochemical 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.
KW - Neutrophil infiltration
KW - Nitric oxide
KW - Shock
UR - http://www.scopus.com/inward/record.url?scp=0036517412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036517412&partnerID=8YFLogxK
M3 - Article
C2 - 11900342
AN - SCOPUS:0036517412
VL - 17
SP - 222
EP - 227
JO - Shock
JF - Shock
SN - 1073-2322
IS - 3
ER -