Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant

Pediatr Pulmonol. 1996 Jul;22(1):14-22. doi: 10.1002/(SICI)1099-0496(199607)22:1<14::AID-PPUL3>3.0.CO;2-K.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Antioxidants / metabolism
  • Bronchoalveolar Lavage / adverse effects
  • Disease Models, Animal
  • Rabbits
  • Reference Values
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / physiopathology
  • Severity of Illness Index
  • Surface-Active Agents / adverse effects*
  • Surface-Active Agents / pharmacology
  • Transferrin / administration & dosage
  • Transferrin / pharmacology*


  • Antioxidants
  • Surface-Active Agents
  • Transferrin