Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic animal model.
Evidence suggests that activated protein C (APC) attenuates acute lung injury (ALI) through antithrombotic and anti-inflammatory mechanisms. The aim of this study was to determine the effects of APC on ALI in adult rats exposed to hyperoxic environment. Rats were divided into control, hyperoxia, hyperoxia + APC, and APC. Hyperoxia and hyperoxia + APC were exposed to 1, 3, and 5 days of hyperoxia. Hyperoxia + APC and APC were injected with APC (5 mg/kg, i.p.) every 12 h. Control and hyperoxia received isotonic sodium chloride solution injection. Measurement of wet to dry ratio and albumin leak demonstrated significant improvement in hyperoxia + APC when compared with hyperoxia. Apoptosis, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, was significantly reduced in hyperoxia + APC when compared with hyperoxia. Histological evaluation of lung sections showed significant reduction in inflammation, edema, and in the number of marginating neutrophils in hyperoxia + APC as compared with hyperoxia. Transcriptional expression of lung inflammatory mediators demonstrated a time-dependent surge in the levels TNF-alpha, IL-1beta, and IL-6 in response to hyperoxia that was attenuated with APC administration in the presence of hyperoxia. In this rat model, APC attenuates lung injury and the expression of inflammatory mediators in ALI secondary to hyperoxia.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. ah51@aub.edu.lb
Ahmad W
AW
Husari
Aline
A
Khayat
Haitham
H
Awdeh
Hadi
H
Hatoum
Michel
M
Nasser
Salman M
SM
Mroueh
Ghazi
G
Zaatari
Marwan
M
El-Sabban
Ghassan S
GS
Dbaibo
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004789:Enzyme Activation; D018496:Hyperoxia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D011486:Protein C / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats
D018836:Inflammation Mediators; D011486:Protein C