Serine antiproteinase administration preserves innate superoxide dismutase levels after acid aspiration and hyperoxia but does not decrease lung injury.
Acute lung injury after acid aspiration and increased ambient oxygen result in significant oxidative damage to the lungs. Lung antioxidant levels are also reduced. Because levels of serine proteinases in the airspaces are also dramatically increased, we hypothesized that these enzymes play a role in degrading lung antioxidants. Rats were treated with a serine proteinase inhibitor, aprotinin, before pulmonary aspiration of acid in the presence of increased ambient oxygen (hyperoxia). Lung Cu/Zn and Mn superoxide dismutase (SOD) activity (by colorimetric assay) and Cu/Zn SOD immune reactive protein (enzyme-linked immunosorbent assay) were assayed. The effects of antiproteinase treatment on acute lung injury were also assessed. Total SOD, Cu/Zn SOD, and Cu/Zn SOD antigenic protein levels were decreased in animals after acid aspiration and hyperoxia. However, Mn SOD activity was unchanged. The decrease in Cu/Zn SOD was attenuated in animals, where serine proteinase activity was inhibited. However, antiproteinase treatment did not decrease acute pulmonary injury, as assessed by leakage of radiolabeled albumin into the lung (permeability index), arterial blood gases, and markers of acute inflammation (pulmonary myeloperoxidase activity, a surrogate neutrophilic marker, and inflammatory cytokine profiles). We conclude that production of serine proteinases play a major role in degrading Cu/Zn SOD, thereby decreasing pulmonary antioxidant capacity. However, the role this plays in the pathogenesis of the acute lung injury is not clear.
Department of Anesthesiology, State University of New York at Buffalo, Buffalo, NY 14215, USA. nnader@buffalo.edu
Nader D
ND
Nader
Bruce A
BA
Davidson
Alan R
AR
Tait
Bruce A
BA
Holm
Paul R
PR
Knight
D000818:Animals; D006863:Hydrogen-Ion Concentration; D018496:Hyperoxia / Q000201:enzymology*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011015:Pneumonia, Aspiration / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D018836:Inflammation Mediators; D015842:Serine Proteinase Inhibitors; D009195:Peroxidase; D013482:Superoxide Dismutase