Effect of tracheal insufflation of deferoxamine on acute ozone toxicity in rats.
To test the hypothesis that deferoxamine (DFO) may protect the lung against the acute toxicity of ozone (O3), male Sprague-Dawley rats (250 to 300 gm) were tracheally insufflated before exposure to O3 (2 ppm for 4 hours) with DFO (25 mg/kg), ferric-DFO, or sterile water. Measurements of bronchoalveolar lavage fluid (BALF) protein, ascorbate, hydrogen peroxide, and lipid hydroperoxides were made immediately after O3 exposure and 12 and 24 hours later. DFO (25 mg/kg) decreased BALF protein concentration (p < 0.05) and was associated with higher BALF ascorbate concentrations (p < 0.01) in O3-exposed animals. Ferric-DFO did not show these protective effects. No peroxides were found in BALF from any control or O3-exposed animals (detection limit: H2O2, 1 pmol; lipid hydroperoxides, 0.3 pmol). Higher DFO doses (50 mg/kg and 100 mg/kg) did not decrease BALF protein concentration immediately after O3 exposure or 12 hours later. Indeed, the highest dose was toxic to O3-exposed animals. Although DFO is able to protect against O3-induced lung damage in rats, apparently by chelating iron, its effect dose range appears to be narrow.
Louie
S
S
Department of Internal Medicine, School of Medicine, University of California, Davis 95616-8542.
Arata
M A
MA
Offerdahl
S D
SD
Halliwell
B
B
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003676:Deferoxamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007327:Insufflation; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects*; D008297:Male; D010126:Ozone / Q000378:metabolism / Q000633:toxicity*; D011506:Proteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011506:Proteins; D010126:Ozone; D003676:Deferoxamine