TY - JOUR
T1 - Beneficial effects of tempol, a membrane-permeable radical scavenger, in a rodent model of splanchnic artery occlusion and reperfusion
AU - Cuzzocrea, Salvatore
AU - McDonald, Michelle C.
AU - Mazzon, Emanuela
AU - Filipe, Helder Mota
AU - Costantino, Giuseppina
AU - Caputi, Achille P.
AU - Thiemermann, Christoph
PY - 2000/8
Y1 - 2000/8
N2 - The aim of the present study was to investigate the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to splanchnic artery occlusion shock (SAO). Rats subjected to SAO developed a significant decrease in mean arterial blood pressure, a significant increase in tissue myeloperoxidase activity, and a marked injury to the distal ileum. SAO shock resulted in 100% mortality at 2 h after reperfusion. At 60 min after reperfusion, a marked increase in the immunoreactivity to nitrotyrosine and to poly (ADP-ribose) synthetase was observed in the necrotic ileum of rats with SAO. Staining of sections of the ileum obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) and anti-P-selectin antibodies resulted in diffuse staining. Tempol (30 mg/kg bolus injection 5 min prior to reperfusion, followed by an infusion of 30 mg/kg/h intravenously) attenuated 1) the infiltration of the reperfused intestine with neutrophils, 2) the lipid peroxidation, 3) the production of peroxynitrite, 4) the degree of P-selectin and ICAM-1 staining in tissue sections from SAO-shocked rats, 5) histological signs of bowel injury, and 6) mortality at 2 h after reperfusion. Taken together, our results clearly demonstrate that the intracellular radical scavenger tempol reduces the intestinal injury of rats subjected SAO shock.
AB - The aim of the present study was to investigate the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to splanchnic artery occlusion shock (SAO). Rats subjected to SAO developed a significant decrease in mean arterial blood pressure, a significant increase in tissue myeloperoxidase activity, and a marked injury to the distal ileum. SAO shock resulted in 100% mortality at 2 h after reperfusion. At 60 min after reperfusion, a marked increase in the immunoreactivity to nitrotyrosine and to poly (ADP-ribose) synthetase was observed in the necrotic ileum of rats with SAO. Staining of sections of the ileum obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) and anti-P-selectin antibodies resulted in diffuse staining. Tempol (30 mg/kg bolus injection 5 min prior to reperfusion, followed by an infusion of 30 mg/kg/h intravenously) attenuated 1) the infiltration of the reperfused intestine with neutrophils, 2) the lipid peroxidation, 3) the production of peroxynitrite, 4) the degree of P-selectin and ICAM-1 staining in tissue sections from SAO-shocked rats, 5) histological signs of bowel injury, and 6) mortality at 2 h after reperfusion. Taken together, our results clearly demonstrate that the intracellular radical scavenger tempol reduces the intestinal injury of rats subjected SAO shock.
KW - Adhesion molecule
KW - Free radicals
KW - ICAM-1
KW - Lipid peroxidation
KW - P-selectin
KW - Peroxynitrite
KW - Splanchnic artery occlusion (SAO) shock
KW - Tempol
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UR - http://www.scopus.com/inward/citedby.url?scp=0034241630&partnerID=8YFLogxK
M3 - Article
C2 - 10947159
AN - SCOPUS:0034241630
VL - 14
SP - 150
EP - 156
JO - Shock
JF - Shock
SN - 1073-2322
IS - 2
ER -