Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species.
Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury.
Okuda
M
M
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia.
Lee
H C
HC
Chance
B
B
Cohen
P J
PJ
Kumar
C
C
D000166:Acridines / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D011312:Pressure; D011651:Pulmonary Artery / Q000503:physiopathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000166:Acridines; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin