title: Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury.
abstract: OBJECTIVE
  Splanchnic artery occlusion shock (SAO) causes an enhanced formation of reactive oxygen species (ROS), which contribute to the pathophysiology of shock. Here we have investigated the effects of n-acetylcysteine (NAC), a free radical scavenger, in rats subjected to SAO shock.
  
  
  RESULTS
  Treatment of rats with NAC (applied at 20 mg/kg, 5 min prior to reperfusion, followed by an infusion of 20 mg/kg/h) attenuated the mean arterial blood and the migration of polymorphonuclear cells (PMNs) caused by SAO-shock. NAC also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase (MPO) and malondialdehyde (MDA) caused by SAO shock in the ileum. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine in the plasma of the SAO-shocked rats after reperfusion. Immunohistochemical analysis for nitrotyrosine and for poly(ADP-ribose) synthetase (PARS) revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from SAO-shocked rats which had received NAC. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localised in the vascular endothelial cells. Ileum tissue section obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. NAC treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats. In addition, in ex vivo studies in aortic rings from shocked rats, we found reduced contractions to noradrenaline and reduced responsiveness to a relaxant effect to acetylcholine (vascular hyporeactivity and endothelial dysfunction, respectively). NAC treatment improved contractile responsiveness to noradrenaline, enhanced the endothelium-dependent relaxations and significantly improved survival.
  
  
  CONCLUSIONS
  Taken together, our results clearly demonstrate that NAC treatment exert a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury.
authors.affiliation: Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario, Via C. Valeria-Gazzi, 98100, Messina, Italy. salvator@www.unime.it
authors.forename: S
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: E
authors.initials: E
authors.lastname: Mazzon
authors.forename: G
authors.initials: G
authors.lastname: Costantino
authors.forename: I
authors.initials: I
authors.lastname: Serraino
authors.forename: A
authors.initials: A
authors.lastname: De Sarro
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007082:Ileum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013157:Splenic Artery; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D000109:Acetylcholine; D000111:Acetylcysteine