title: Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant.
abstract: In respiratory failure, transferrin (TF) with variable iron saturation accumulates in the alveolar space. Binding free iron to TF may inhibit metal-catalyzed formation of free radicals. The aim of this study was to evaluate whether the degree of the iron-saturation of TF influences the severity of respiratory failure and surfactant responsiveness. Surfactant deficiency and lung edema was induced in 42 paralyzed and ventilated young rabbits by bronchoalveolar lavage (BAL); 19 of these animals were preexposed to 100% O2 for 40 hours. The animals received (1) exogenous surfactant intratracheally (100 mg/kg in 4 ml/kg saline); (2) surfactant and Fe(3+)-TF (50 or 25 mg/kg); or (3) surfactant and iron-free TF (50 mg/kg). One hour after administration of TF, 13-25% of exogenous TF was recovered by BAL. Administration of Iron-free TF significantly decreased the iron saturation of TF in BAL. In acute respiratory failure induced by BAL, Fe(3+)-TF decreased the efficacy of exogenous surfactant in improving the gas exchange, and increased surfactant inhibition, while iron-free TF had no effect. By contrast, in respiratory failure induced by hyperoxia and BAL, iron-free TF improved the efficacy of exogenous surfactant, but Fe(2+)-TF had no effect. After administration of iron-free TF, surfactant isolated from BAL was more surface-active than surfactant from BAL of the other hyperoxia-treated animals. In animals exposed to hyperoxia, treatment with iron-free TF decreased malondialdehyde content of BAL. We propose that low iron saturation of TF decreases oxidant stress and favors the recovery from respiratory failure.
authors.affiliation: Department of Pediatrics, University of California, Irvine 92717-4475, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hallman
authors.forename: V
authors.initials: V
authors.lastname: Chundu
authors.forename: M
authors.initials: M
authors.lastname: Barsotti
authors.forename: K
authors.initials: K
authors.lastname: Bry
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D018893:Bronchoalveolar Lavage / Q000009:adverse effects; D004195:Disease Models, Animal; D011817:Rabbits; D012016:Reference Values; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D013501:Surface-Active Agents / Q000009:adverse effects* / Q000494:pharmacology; D014168:Transferrin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013501:Surface-Active Agents; D014168:Transferrin