Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung injury

Inflamm Res. 2012 Jul;61(7):699-705. doi: 10.1007/s00011-012-0462-6. Epub 2012 Mar 23.

Abstract

Objective: Pulmonary complications are frequent during acute pancreatitis (AP). We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile-pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h before and 1 h after AP.

Methods: Amylase activity was measured in plasma. Lungs were harvested for mRNA expression analysis of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and histological examination.

Results: Hyperamylasemia was reduced by NAC in both AP models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc-induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in severe AP.

Conclusions: Although NAC treatment down-regulated inflammatory mediators in lungs during AP it did not prevent leukocyte infiltration, which could be responsible for maintaining the lung injury. As a result, NAC aggravated the lung damage in severe AP and failed to exert beneficial effects in the mild disease model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Amylases / blood
  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CXCL1 / genetics
  • Disease Models, Animal
  • Free Radical Scavengers / therapeutic use*
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / drug therapy*
  • Lung Injury / etiology
  • Lung Injury / metabolism
  • Lung Injury / pathology
  • Male
  • Pancreatitis / chemically induced
  • Pancreatitis / complications*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Peroxidase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Taurocholic Acid

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • Free Radical Scavengers
  • RNA, Messenger
  • Taurocholic Acid
  • Peroxidase
  • Amylases
  • Acetylcysteine