Oxidative inactivation of surfactants

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