Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice

Autor: Yves Berthiaume, Mélissa Aubin Vega, Cécile Chupin, Emmanuelle Brochiero, Mihai Pascariu, Anik Privé, André Dagenais
Rok vydání: 2019
Předmět:
Male
ARDS
Physiology
Alveolar Epithelium
Immunology
Anti-Inflammatory Agents
dexamethasone
Inflammation
030204 cardiovascular system & hematology
Pharmacology
Lung injury
Bleomycin
lcsh:Physiology
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Physiology (medical)
Edema
Animals
Outbred Strains
Acute lung injury
medicine
Animals
Diffuse alveolar damage
Lung
Dexamethasone
Original Research
Respiratory Distress Syndrome
Respiratory Conditions Disorder and Diseases
bleomycin
lcsh:QP1-981
business.industry
Pneumonia
acute respiratory distress syndrome
respiratory system
medicine.disease
respiratory tract diseases
3. Good health
Disease Models
Animal
chemistry
inflammation
Alveolar Epithelial Cells
repair
Inflammation Mediators
medicine.symptom
business
edema
030217 neurology & neurosurgery
medicine.drug
Zdroj: Physiological Reports, Vol 7, Iss 21, Pp n/a-n/a (2019)
Physiological Reports
ISSN: 2051-817X
DOI: 10.14814/phy2.14253
Popis: Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and experimental models of ALI. These studies produced contradictory results. Therefore, our aim was to investigate the effects of dexamethasone in an animal model of bleomycin‐induced acute lung injury and then to determine if the lack of response could be related to an impairment in repair ability of alveolar epithelial cells after injury. NMRI mice were challenged with bleomycin and then treated daily with dexamethasone or saline. Bronchoalveolar lavages (BAL) and lungs were collected for assessment of the inflammatory response and wet/dry ratio (lung edema) and for histological analyses. The effect of bleomycin and dexamethasone on wound repair was also evaluated in vitro on primary alveolar epithelial cell (ATII) cultures. Our data first showed that dexamethasone treatment did not reduce the weight loss or mortality rates induced by bleomycin. Although the TNF‐α level in BAL of bleomycin‐treated mice was reduced by dexamethasone, the neutrophil infiltration remained unchanged. Dexamethasone also failed to reduce lung edema and damage scores. Finally, bleomycin elicited a time‐ and dose‐dependent reduction in repair rates of ATII cell cultures. This inhibitory effect was further enhanced by dexamethasone, which also affected the expression of β3‐ and β6‐integrins, key proteins of alveolar repair. Altogether, our data indicate that the inability of dexamethasone to improve the resolution of ALI might be due to his deleterious effect on the alveolar epithelium repair.
Our data indicates that the inability of dexamethasone to improve the resolution of bleomycin outcomes, in particular, mortality rates, neutrophil infiltration and lung edema, may be due to the remaining alveolar damage observed at day 7 and repair impairment induced by dexamethasone.
Databáze: OpenAIRE
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