Beneficial effects of tempol, a membrane-permeable radical scavenger, in a rodent model of splanchnic artery occlusion and reperfusion.
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.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
McDonald
M C
MC
Mazzon
E
E
Filipe
H M
HM
Costantino
G
G
Caputi
A P
AP
Thiemermann
C
C
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D002445:Celiac Artery; D002463:Cell Membrane Permeability; D003250:Constriction; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction; D016166:Free Radical Scavengers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007082:Ileum / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D017538:Mesenteric Artery, Superior; D009566:Nitrates / Q000378:metabolism; D019007:P-Selectin / Q000032:analysis; D009195:Peroxidase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013113:Spin Labels; D013152:Splanchnic Circulation
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009566:Nitrates; D019007:P-Selectin; D013113:Spin Labels; D018799:Intercellular Adhesion Molecule-1; C039642:peroxynitric acid; D008315:Malondialdehyde; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; C001803:tempol