title: Intravenous dexamethasone attenuated inflammation and influenced apoptosis of lung cells in an experimental model of acute lung injury.
abstract: Acute lung injury (ALI) is characterized by diffuse alveolar damage, inflammation, and transmigration and activation of inflammatory cells. This study evaluated if intravenous dexamethasone can influence lung inflammation and apoptosis in lavage-induced ALI. ALI was induced in rabbits by repetitive saline lung lavage (30 ml/kg, 9+/-3-times). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with dexamethasone i.v. (0.5 mg/kg, Dexamed; ALI+DEX), and healthy non-ventilated controls (Control). After following 5 h of ventilation, ALI animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated. Lung edema was expressed as wet/dry weight ratio. Concentrations of IL-1beta, IL-8, esRAGE, S1PR3 in the lung were analyzed by ELISA methods. In right lung, apoptotic cells were evaluated by TUNEL assay and caspase-3 immunohistochemically. Dexamethasone showed a trend to improve lung functions and histopathological changes, reduced leak of neutrophils (P<0.001) into the lung, decreased concentrations of pro-inflammatory IL-1beta (P<0.05) and marker of lung injury esRAGE (P<0.05), lung edema formation (P<0.05), and lung apoptotic index (P<0.01), but increased immunoreactivity of caspase-3 in the lung (P<0.001). Considering the action of dexamethasone on respiratory parameters and lung injury, the results indicate potential of this therapy in ALI.
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic. mokra@jfmed.uniba.sk.
authors.forename: P
authors.initials: P
authors.lastname: Kosutova
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.forename: S
authors.initials: S
authors.lastname: Balentova
authors.forename: M
authors.initials: M
authors.lastname: Adamkov
authors.forename: M
authors.initials: M
authors.lastname: Kolomaznik
authors.forename: A
authors.initials: A
authors.lastname: Calkovska
authors.forename: D
authors.initials: D
authors.lastname: Mokra
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007262:Infusions, Intravenous; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D003907:Dexamethasone