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. Ferrlc-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 effective dose range appears to be narrow.