title: N-acetylcysteine administration confers lung protection in different phases of lung ischaemia-reperfusion injury.
abstract: OBJECTIVE
  To verify the effects of N-acetylcysteine (NAC) administered before and after ischaemia in an animal model of lung ischaemia-reperfusion (IR) injury.
  
  
  METHODS
  Twenty-four Wistar rats were subjected to an experimental model of selective left pulmonary hilar clamping for 45 min followed by 2 h of reperfusion. The animals were divided into four groups: control group (SHAM), ischaemia-reperfusion, N-acetylcysteine-preischaemia (NAC-Pre) and NAC-postischaemia (NAC-Post). We recorded the haemodynamic parameters, blood gas analysis and histology. We measured the thiobarbituric acid reactive substances concentration; the expression of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), nitrotyrosine, cleaved caspase 3, nuclear factor κB (NF-κB), NF-kappa-B inhibitor alpha (IκB-α), tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β); myeloperoxidase activity (MPO).
  
  
  RESULTS
  No significant differences were observed in the haemodynamic parameters, blood gas analysis and SOD activity among the groups. Lipid peroxidation was significantly higher in the IR and NAC-Pre groups (P < 0.01). The expression of nitrotyrosine, cleaved caspase 3, NF-κB, IκB-α, TNF-α and IL-1β were significantly higher in the IR group when compared with the SHAM and NAC groups (P < 0.01). The NAC-Pre group showed a significantly higher expression of these proteins when compared with the SHAM and NAC-Post groups (P < 0.05). After reperfusion, the expression of iNOS increased almost uniformly in all groups when compared with the SHAM group (P < 0.01). The histological analysis showed fewer inflammatory cells in the NAC groups.
  
  
  CONCLUSIONS
  The intravenous administration of NAC demonstrated protective properties against lung IR injury. The use of NAC immediately after reperfusion potentiates its protective effects.
authors.affiliation: Postgraduate Program of Pulmonology (Federal University of Rio Grande do Sul - UFRGS) Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Forgiarini
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Luiz Alberto
authors.initials: LA
authors.lastname: Forgiarini
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Darlan Pase
authors.initials: DP
authors.lastname: da Rosa
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Mariel Barbachan E
authors.initials: MB
authors.lastname: Silva
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Mariano
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Artur de Oliveira
authors.initials: Ade O
authors.lastname: Paludo
authors.affiliation: Department of Thoracic Surgery, Laboratory of Airway and Lung, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil cristianofa@gmail.com.
authors.forename: Cristiano Feijó
authors.initials: CF
authors.lastname: Andrade
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D061605:Administration, Intravenous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D053148:Caspase 3 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D051550:I-kappa B Kinase; C505410:Casp3 protein, rat; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Inflammation; Ischaemia–reperfusion; N-Acetylcysteine