Protective effect of exogenous transferrin against hyperoxia: a study on premature rabbits

We hypothesized that an increase in plasma iron binding capacity would decrease the generation of oxygen radicals and of lipid peroxides. To test this hypothesis, we studied whether supplementation of transferrin (TF) in premature rabbits would modify the degree of hyperoxic lung injury. Animals, delivered prematurely at 29 days of gestation (term 31 days), were randomized and given either 0.5 g/kg of albumin (Alb) (n = 116) or 0.5 g/kg of iron-free TF (n = 132) intravenously within 2 hours after birth. Another group was randomized to receive saline (n = 15), or either 0.35 g/kg (n = 12) or 0.70 g/kg of iron-free TF (n = 8). After exposure to a 100% oxygen environment for 2 or 4 days, the animals were killed, and plasma and bronchoalveolar lavage (BAL) fluid was recovered. Infusion of TF caused a dose-dependent increase in the concentration of TF and an increase in the unsaturated iron-binding capacity. Administration of TF at birth increased the gradient of TF between serum and alveolar epithelial lining fluid on day 4, suggesting decreased alveolar-capillary permeability. BAL fluid and plasma from TF-supplemented animals contained less lipid peroxidation products and more inhibitor of lipid peroxidation than BAL fluid or plasma from Alb-treated animals. In TF-treated animals, the recovery of protein in BAL fluid (TF group, 1.26 +/- 0.07 mg; Alb group, 1.78 +/- 0.10 mg; P = 0.02) and the water content of the extravascular lung tissue (TF group, 78.5 +/- 1.4%; Alb group, 83.2 +/- 1.3%; P = 0.05) were lower than in Alb-treated animals. We propose that supplementation of iron-free TF decreases iron-catalyzed redox reactions and may decrease hyperoxic lung injury in the premature.