Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by curosurf and N-acetylcysteine.

Abstract

Airborne exposure to lung-toxic agents may damage the lung surfactant system and epithelial and endothelial cells, resulting in a life-threatening pulmonary edema that is known to be refractory to treatment. The aim of this study was to investigate in rats (1) the respiratory injury caused by nose-only exposure to perfluoroisobutene (PFIB), and (2) the therapeutic efficacy of a treatment at 4 and/or 8 h after exposure consisting of the natural surfactant Curosurf and/or the anti-inflammatory drug N-acetylcysteine (NAC). For that purpose, the following parameters were examined: respiratory frequency (RF), lung compliance (Cdyn), airway resistance (Raw), lung wet weight (LWW), airway histopathology; and in brochoalveolar lavage (BAL) fluid, total protein, total phospholipid, cell count and differentiation, and changes in the surface tension of the BAL fluid. The mean (+/- SEM) surface tension of BAL fluid derived from PFIB-exposed (C . t = 1100-1200 mg min(-1) m(-3), approximately 1LCt50; t = 20 min) animals at 24 h following exposure (11 +/- 3 mN/m) was higher than that of unexposed rats (0.8 +/- 0.4 mN/m), reflecting damage to the surfactant system and justifying treatment with exogenous surfactant. Curosurf treatment (62.5 mg/kg i.t.) decreased pulmonary edema caused by PFIB, reflected by a decreased LWW, and decreased the amount of protein in BAL fluid. NAC treatment (1000 mmol/kg ip) inhibited the interstitial pneumonia reflected by a decreased percentage of neutrophils in the alveolar space. It was concluded that a combined treatment of Curosurf + NAC improved respiration, that is, RF and Cdyn, whereby Curosurf predominantly decreased pulmonary edema and NAC predominantly reduced the inflammatory process. A combined treatment may therefore be considered a promising therapeutic approach in early-stage acute respiratory distress caused by PFIB, although the treatment regimes need further investigation.

• Authors: Herman P M van Helden, Dory van de Meent, John P Oostdijk, Marloes J A Joosen, Joep H M van Esch, Arnold H Hammer, Robert V Diemel
• Journal: Inhalation toxicology (Inhal Toxicol) Vol. 16 Issue 8 Pg. 549-64 (Jul 2004) ISSN: 0895-8378 [Print] England
• PMID: 15204746 (Publication Type: Journal Article)

Chemical References

• Biological Products
• Expectorants
• Fluorocarbons
• Phospholipids
• Proteins
• perfluoroisobutylene
• poractant alfa
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Administration, Inhalation
• Animals
• Animals, Outbred Strains
• Biological Products (therapeutic use)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Drug Therapy, Combination
• Expectorants (therapeutic use)
• Fluorocarbons (administration & dosage, toxicity)
• Inhalation Exposure
• Lung (drug effects, pathology, physiopathology)
• Male
• Organ Size (drug effects)
• Phospholipids (analysis, therapeutic use)
• Proteins (analysis)
• Pulmonary Edema (etiology, physiopathology, prevention & control)
• Rats
• Rats, Wistar
• Respiratory Function Tests
• Specific Pathogen-Free Organisms
• Surface Tension (drug effects)