title: N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by Hemorrhagic Shock in a Porcine Model.
abstract: OBJECTIVE
  To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock.
  
  
  METHODS
  Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period. During shock, the mean arterial pressure (MAP) was maintained at 30-40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and colloids (18 mL/kg) targeting to MAP normalization (baseline values ± 10%). In addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls and glutathione peroxidase (GPx) activity were determined in lung tissue homogenates. Also, histological examination of pulmonary tissue specimens was performed.
  
  
  RESULTS
  TBARS were higher in Group-B than in Group-A or Group-C: 2.90 ± 0.47, 0.57 ± 0.10, 1.78 ± 0.47 pmol/μg protein, respectively (p < 0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group-C: 3.22 ± 0.68, 0.89 ± 0.30, 1.95 ± 0.54 nmol/mg protein, respectively (p > 0.05). GPx activity did not differ significantly between the three groups (p > 0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar collapse, interstitial edema and inflammation.
  
  
  CONCLUSIONS
  NAC plus DFX prevented the increase of pulmonary oxidative stress markers and protein damage after resuscitated hemorrhagic shock and had beneficial effect on lung histology. NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock, since it may significantly prevent free radical injury in the lung.
authors.affiliation: a 1st Department of Anesthesiology, Aretaieio Hospital , University of Athens, School of Medicine , Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mani
authors.affiliation: a 1st Department of Anesthesiology, Aretaieio Hospital , University of Athens, School of Medicine , Greece.
authors.forename: Chryssoula
authors.initials: C
authors.lastname: Staikou
authors.affiliation: b 4th Department of Surgery, Attikon Hospital , School of Medicine , Greece.
authors.forename: Iosifina
authors.initials: I
authors.lastname: Karmaniolou
authors.affiliation: b 4th Department of Surgery, Attikon Hospital , School of Medicine , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Orfanos
authors.affiliation: b 4th Department of Surgery, Attikon Hospital , School of Medicine , Greece.
authors.forename: Anastassios
authors.initials: A
authors.lastname: Mylonas
authors.affiliation: c Department of Science of Nutrition-Dietetics , Harokopio University of Athens , Greece.
authors.forename: Tzortzis
authors.initials: T
authors.lastname: Nomikos
authors.affiliation: d 1st Department of Pathology, Aretaieio Hospital , University of Athens, School of Medicine , Greece.
authors.forename: Agathi
authors.initials: A
authors.lastname: Pafiti
authors.affiliation: e Experimental-Research Center ELPEN Pharmaceuticals , Athens , Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: b 4th Department of Surgery, Attikon Hospital , School of Medicine , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.affiliation: b 4th Department of Surgery, Attikon Hospital , School of Medicine , Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
authors.affiliation: a 1st Department of Anesthesiology, Aretaieio Hospital , University of Athens, School of Medicine , Greece.
authors.forename: Kassiani
authors.initials: K
authors.lastname: Theodoraki
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003102:Colloids; D000077324:Crystalloid Solutions; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005440:Fluid Therapy / Q000379:methods; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D007552:Isotonic Solutions / Q000008:administration & dosage; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D011897:Random Allocation; D015532:Rehydration Solutions / Q000008:administration & dosage; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy*; D017262:Siderophores / Q000627:therapeutic use*; D013552:Swine; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D015415:Biomarkers; D003102:Colloids; D000077324:Crystalloid Solutions; D016166:Free Radical Scavengers; D007552:Isotonic Solutions; D015532:Rehydration Solutions; D017262:Siderophores; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D003676:Deferoxamine; D000111:Acetylcysteine
keywords: N-Acetylcysteine; desferoxamine; hemorrhagic shock; lungs; oxidative stress