title: Modulation of normobaric pulmonary oxygen toxicity by hydroxyl radical inhibition.
abstract: 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)
authors.affiliation: Department of Respiratory Medicine, Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: N W
authors.initials: NW
authors.lastname: Boyce
authors.forename: D
authors.initials: D
authors.lastname: Campbell
authors.forename: S R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: 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
chemical_list: D006878:Hydroxides; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D013890:Thiourea; D003676:Deferoxamine; D010100:Oxygen