Anti-inflammatory and anti-fibrotic treatment in a rodent model of acute lung injury induced by sulfur dioxide.
Clin Toxicol (Phila)
; 56(12): 1185-1194, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-29923422
ABSTRACT
CONTEXT Inhalation of sulfur dioxide (SO2) affects the lungs and exposure to high concentrations can be lethal. The early pulmonary response after inhaled SO2 involves tissue injury, acute neutrophilic lung inflammation and airway hyperresponsiveness (AHR). In rats, long-term pulmonary fibrosis is evident 14 days post-exposure as indicated by analysis of collagen deposition in lung tissue. Early treatment with a single dose of dexamethasone (DEX,10 mg/kg) significantly attenuates the acute inflammatory response in airways. However, this single DEX-treatment is not sufficient for complete protection against SO2-induced injuries. METHODS:
Female Sprague-Dawley rats exposed to SO2 (2200 ppm, nose-only exposure, 10 min) were given treatments (1, 5 and 23 h after SO2-exposure) with the anti-fibrotic and anti-inflammatory substance Pirfenidone (PFD, 200 mg/kg) or DEX (10 mg/kg) to evaluate whether the inflammatory response, AHR and lung fibrosis could be counteracted.RESULTS:
Both treatment approaches significantly reduced the total leukocyte response in bronchoalveolar lavage fluid and suppressed pulmonary edema. In contrast to DEX-treatment, PFD-treatment reduced the methacholine-induced AHR to almost control levels and partially suppressed the acute mucosal damage whereas multiple DEX-treatment was the only treatment that reduced collagen formation in lung tissue.CONCLUSIONS:
To enable an accurate extrapolation of animal derived data to humans, a detailed understanding of the underlying mechanisms of the injury, and potential treatment options, is needed. The findings of the present study suggest that treatments with the capability to reduce both AHR, the inflammatory response, and fibrosis are needed to achieve a comprehensive mitigation of the acute lung injury caused by SO2.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Dióxido de Enxofre
/
Poluentes Ocupacionais do Ar
/
Lesão Pulmonar Aguda
/
Anti-Inflamatórios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Clin Toxicol (Phila)
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suécia