Divalent Cation-Chelator Complexes Protect Surface Active Properties of Pulmonary Surfactant Against Oxidative Injury by Reactive Oxygen Species

Abstract 1852 Poster Session IV, Tuesday, 5/4 (poster 337)

Little is known about in vitro antioxidant properties of divalent cation-chelator complexes, such as iron-deferoxamine and calcium-EDTA. However, these complexes may have antioxidant properties by stabilizing the surfactant protein moities against attack by reactive oxygen species (ROS). We hypothesized that inactivation of surface active properties of pulmonary surfactant (PS) by ROS could be prevented by iron-deferoxamine or calcium-EDTA complexes. We prepared 0.5 mg phospholipid/mL suspension of modified bovine pulmonary surfactant (Newfactan, Yuhan Pharm, Korea) and reacted with 1 mM H₂O₂ or NaOCl either in presence or absence of 1 mM iron-deferoxamine or calcium-EDTA complexes. Pulsating bubble surfactometer was used to measure in vitro Min. and Max. surface tensions (ST) after 5 min of pulsation, hysteresis and standardized area-under-the-curve (AUC_s) of area-surface tension diagram, and 1 s adsorption. For mixtures of PS and 1 mM H₂O₂ and/or 1 mM NaOCl (a), adsorption, 5-min Min and Max ST increased significantly; AUC_s decreased significantly compared to PS control (p < 0.05); and hysteresis curve was deformed. (Figure)

Fig 1

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In presence of 1 mM iron-deferoxamine (b) or calcium-EDTA complexes (c), when reacted with ROS, adsorption, 5-min Min and Max ST were significantly lower than mixtures of PS and ROS (p<0.01) but similar to PS control (d), and hysteresis curve was intact with AUC_s slightly higher than PS control. In conclusion, aggravation of surface active properties of surfactant by H₂O₂ or NaOCl was not seen when iron-deferoxamine or calcium-EDTA complexes was added simultaneously. We speculate that these divalent cation-chelator complexes given simultaneously with pulmonary surfactant may protect against inactivation of surface active properties by ROS.