Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion

Emanuela Mazzon, Laura Dugo, Angelina De Sarro, Jia He Li, Achille P. Caputi, Jie Zhang, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)222-227
Number of pages6
JournalShock
Volume17
Issue number3
StatePublished - Mar 2002
Externally publishedYes

Fingerprint

Viscera
Reperfusion
Arteries
Arterial Pressure
Intercellular Adhesion Molecule-1
Shock
P-Selectin
Ileum
Superior Mesenteric Artery
Poly(ADP-ribose) Polymerases
Neutrophil Infiltration
Constriction
Abdomen
Peroxidase
Intestines
Poly(ADP-ribose) Polymerase Inhibitors
GPI 6150
Mortality
Wounds and Injuries

Keywords

  • Neutrophil infiltration
  • Nitric oxide
  • Shock

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Mazzon, E., Dugo, L., De Sarro, A., Li, J. H., Caputi, A. P., Zhang, J., & Cuzzocrea, S. (2002). Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion. Shock, 17(3), 222-227.

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 journalArticle

Mazzon, E, Dugo, L, De Sarro, A, Li, JH, Caputi, AP, Zhang, J & Cuzzocrea, S 2002, 'Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion', Shock, vol. 17, no. 3, pp. 222-227.
Mazzon, Emanuela ; Dugo, Laura ; De Sarro, Angelina ; Li, Jia He ; Caputi, Achille P. ; Zhang, Jie ; Cuzzocrea, Salvatore. / Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion. In: Shock. 2002 ; Vol. 17, No. 3. pp. 222-227.
@article{b5406aa8a5ed49d891f87445aaccc65d,
title = "Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion",
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.",
keywords = "Neutrophil infiltration, Nitric oxide, Shock",
author = "Emanuela Mazzon and Laura Dugo and {De Sarro}, Angelina and Li, {Jia He} and Caputi, {Achille P.} and Jie Zhang and Salvatore Cuzzocrea",
year = "2002",
month = "3",
language = "English (US)",
volume = "17",
pages = "222--227",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

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 -