Oxidative inactivation of surfactants

Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL4 surfactant (KL4). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO-) or 0.5 mM hypochlorous acid (OCl-), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant > KL4 > NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p < 0.01) but lower concentration of malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL4 than in beractant (p < 0.05). Surface area cycling for 24 h with 2 mM ONOO- or 0.5 mM OCl- caused both beractant and KL4 to increase the proportion of light subtypes from 8-10% to 26-29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74-91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease.