Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by Curosurf and N-acetylcysteine
article
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, ∼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.
Topics
Antiinflammatory agentIsobutyleneLung surfactantPerfluoroisobutenePhospholipidPoractantProteinToxic substanceUnclassified drugAirway resistanceAnimal experimentAnimal modelAnimal tissueBreathing rateCell countCell differentiationControlled studyDrug efficacyDrug indicationExposureHistopathologyInterstitial pneumoniaLung alveolus epitheliumLung complianceLung edemaLung endotheliumLung lavageLung weightMaleRatRespiratory distressRespiratory tract diseaseSurface tensionAdministration, InhalationAnimalsAnimals, outbred strainsBiological productsBronchoalveolar lavage lluidDrug therapy, combinationExpectorantsFluorocarbonsInhalation exposureLungMaleOrgan sizePhospholipidsPulmonary EdemaRats, wistarRespiratory function testsSpecific pathogen-free organismsSurface tensionAnimaliaAcetylcysteine, 616-91-1Isobutylene, 115-11-7Lung surfactant, 99732-49-7Protein, 67254-75-5Perfluoroisobutylene, 382-21-8Poractant alfa, 129069-19-8
TNO Identifier
237892
ISSN
08958378
Source
Inhalation Toxicology, 16(8), pp. 549-564.
Pages
549-564
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