Modulation of normobaric pulmonary oxygen toxicity by hydroxyl radical inhibition.
The effects of hydroxyl radical inhibition on an experimental model of normobaric pulmonary oxygen toxicity have been studied. The metal ion chelator, desferrioxamine (which inhibits hydroxyl-radical generation) or the hydroxyl-radical scavenger, dimethylthiourea (DMTU), were administered in an attempt to block hydroxyl-radical-mediated tissue injury. Lung injury was monitored in Sprague-Dawley rats by examining lung histology and bronchoalveolar lavage and by assessing pulmonary capillary permeability using the 125I-albumin lung permeability index and the lung weight:body weight ratio. Control animals had lung permeability indices 0.183 +/- 0.005 and lung weight to body weight ratio of 4.50 +/- 0.10 (all as mean +/- SEM). With increased duration of exposure to hyperoxia, there was a progressive increase in pulmonary inflammation, with thickening of alveolar membranes and atelectasis and a progressive increase in lung permeability indices (0.434 +/- 0.088 at 24 hrs; 0.954 +/- 0.165 at 48 hrs; and 1.55 +/- 0.214 at 60 hrs); and lung weight to body weight ratio (5.28 +/- 0.11 at 24 hrs; 6.54 +/- 0.23 at 48 hrs; and 8.91 +/- 0.51 at 60 hrs). Treatment with desferrioxamine provided significant protection from lung injury after 24 hrs of hyperoxia (eg., lung permeability indices 0.250 +/- 0.018; lung weight to body weight ratio 4.68 +/- 0.14, both p less than 0.025; cf. 24-hr hyperoxia controls) but no reduction in pulmonary injury was observed after 48 and 60 hrs of hyperoxia exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Boyce
N W
NW
Department of Respiratory Medicine, Queen Elizabeth Hospital, Adelaide, Australia.
Campbell
D
D
Holdsworth
S R
SR
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003676:Deferoxamine / Q000627:therapeutic use*; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D006878:Hydroxides; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D013890:Thiourea; D003676:Deferoxamine; D010100:Oxygen