Cifuentes J, Ruiz-Oronoz J, Myles C, Nieves B, Carlo W A, Matalon S
Department of Pediatrics, University of Alabama at Birmingham 35233, USA.
J Appl Physiol (1985). 1995 May;78(5):1800-5. doi: 10.1152/jappl.1995.78.5.1800.
Increased concentrations of partially reduced oxygen and nitrogen reactive species damage the alveolar epithelium and either cause or exacerbate surfactant deficiency. For this reason, there is a quest to identify surfactant replacement mixtures, which in addition to repleting depleted surfactant stores can also reduce the steady-state concentrations of reactive species in the alveolar space. Herein, we evaluated the ability of natural lung surfactant (NLS) and two mixtures (Exosurf and Survanta) used clinically for the correction of surfactant deficiency to scavenge hydroxyl radical-type species (.OH), generated either by the decomposition of peroxynitrite or by Fenton reagents (FeCl3 + H2O2). Exosurf or Survanta decreased .OH only when present at high lipid concentrations (6.5 mM). On the other hand, 40 microM of NLS decreased .OH concentrations from 75 +/- 2 to 53 +/- 2 microM (P < 0.05), most likely because of the interaction of .OH with protein sulfhydryl groups. Similarly, 40 microM of NLS incubated with a bolus of H2O2 (400 microM) decreased the H2O2 concentration in the supernatant by approximately 50%, due to the presence of catalase-type activity. In contrast to NLS, neither Exosurf nor Survanta scavenged H2O2, even when present at millimolar lipid concentrations. We concluded that Exosurf and Survanta contain limited antioxidant activity compared with NLS.
部分还原的氧和氮反应性物质浓度升高会损害肺泡上皮,并导致或加剧表面活性剂缺乏。因此,人们一直在寻求确定表面活性剂替代混合物,这种混合物除了补充耗尽的表面活性剂储备外,还能降低肺泡腔内反应性物质的稳态浓度。在此,我们评估了天然肺表面活性剂(NLS)以及临床上用于纠正表面活性剂缺乏的两种混合物(Exosurf和Survanta)清除由过氧亚硝酸盐分解或芬顿试剂(FeCl3 + H2O2)产生的羟基自由基型物质(·OH)的能力。只有当脂质浓度高时(6.5 mM),Exosurf或Survanta才会降低·OH。另一方面,40 μM的NLS可将·OH浓度从75±2 μM降至53±2 μM(P < 0.05),这很可能是由于·OH与蛋白质巯基的相互作用。同样,40 μM的NLS与一大剂量的H2O2(400 μM)孵育后,由于过氧化氢酶型活性的存在,上清液中的H2O2浓度降低了约50%。与NLS相反,即使Exosurf和Survanta的脂质浓度达到毫摩尔级别,它们也不能清除H2O2。我们得出结论,与NLS相比,Exosurf和Survanta的抗氧化活性有限。