The effects of hyperoxia exposure on lung function and pulmonary surfactant in a rat model of acute lung injury.
The objective of this study was to determine if prolonged hyperoxia exposure would deplete antioxidants, resulting in excessive oxidative stress that would lead to oxidation of pulmonary surfactant and contribute to lung dysfunction. Rats were exposed to either hyperoxic (> 95% O(2)) or normoxic (21% O(2)) oxygen concentrations for 48 or 60 hours. Pulmonary compliance, inflammatory cells, and total protein levels were measured as indicators of lung injury. Bronchoalveolar lavage (BAL) samples were analyzed for surfactant composition, antioxidant content, and markers of oxidative stress. Antioxidants were also measured in lung tissue and plasma samples. Hyperoxia exposure for 60 hours resulted in increased protein and inflammatory cells in BAL, and lower pulmonary compliance, compared to all other groups. Total surfactant and surfactant large aggregates were increased following 48 hours of hyperoxia exposure, with a further increase following 60 hours. Animals exposed to 60 hours of hyperoxia also demonstrated lower ascorbate levels in lung tissue, increased lipid peroxides in BAL, and increased oxidation of phosphatidylglycerol species in surfactant. This study demonstrates that the balance of oxidant/antioxidant components is disrupted within the lung during periods of hyperoxia, and that although surfactant lipids may be susceptible to oxidative damage, they do not likely represent a major mechanism for the lung dysfunction observed.
Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
Patrick W
PW
Pace
Li-Juan
LJ
Yao
John X
JX
Wilson
Fred
F
Possmayer
Ruud A W
RA
Veldhuizen
James F
JF
Lewis
D055371:Acute Lung Injury / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology*; D008170:Lung Compliance; D008297:Male; D018384:Oxidative Stress; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014527:Uric Acid / Q000097:blood
D000975:Antioxidants; D015415:Biomarkers; D008054:Lipid Peroxides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D014527:Uric Acid; D001205:Ascorbic Acid