title: Protective effects of N-acetyl-L-cysteine and platelet activating factor inhibition are not linked to intercellular adhesion molecule-1 expression after intestinal ischemia and reperfusion injury in rats.
abstract: BACKGROUND
  Intestinal ischemia and reperfusion (I/R) injury may result in development of the systemic inflammatory response syndrome (SIRS). The interactions between activated leukocytes and endothelial cells, mediated by adhesion molecules, seem to be pivotal in these conditions, leading as they do to extravasation of circulating leukocytes within the inflamed tissue. The intercellular adhesion molecule-1 (ICAM-1) mediating firm adhesion of activated leukocytes is upregulated in many organs after I/R injury, but the regulatory mechanisms are complex and have not been fully investigated.
  
  
  METHODS
  We evaluated whether ICAM-1 expression was linked with a potential protective effect of N-acetyl-L-cysteine (NAC) and the platelet activating factor (PAF) inhibitor (Lexipafant), administered 15 min after the start of reperfusion, in a model of intestinal ischemia (40 min) and reperfusion (12 h) in the rat.
  
  
  RESULTS
  ICAM-1 expression increased significantly in the ileum, colon, lungs and pancreas after intestinal I/R. Treatments with NAC and the PAF inhibitor did not affect this response. An increased endothelial albumin-leakage was observed in the same organs after I/R. Treatment with NAC reduced the endothelial leakage of albumin in the ileum, colon and lungs, whereas administration of the PAF inhibitor alone demonstrated a protective effect only in the ileum. Furthermore, neutrophil sequestration in the lungs and IL-1beta levels in plasma increased significantly after I/R, and these changes were markedly reduced by both treatment regimes.
  
  
  CONCLUSIONS
  The protective effect of NAC and the PAF inhibitor Lexipafant in intestinal I/R injury is not due to a decreased expression of ICAM-1.
authors.affiliation: Dept. of Anesthesiology, Lund University Hospital, Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Olanders
authors.forename: A
authors.initials: A
authors.lastname: Börjesson
authors.forename: Z W
authors.initials: ZW
authors.lastname: Sun
authors.forename: R
authors.initials: R
authors.lastname: Andersson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D019610:Cytoprotection / Q000276:immunology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects; D007511:Ischemia / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D007093:Imidazoles; D007375:Interleukin-1; D010972:Platelet Activating Factor; D018799:Intercellular Adhesion Molecule-1; D007930:Leucine; C103289:lexipafant; D000111:Acetylcysteine