Increased F-2 isoprostanes in the acute chest syndrome of sickle cell disease as a marker of oxidative stress

Nitric oxide metabolism is altered during the acute chest syndrome of sickl e cell disease. In the presence of oxygen and oxygen-related molecules, nit ric oxide can preferentially form the powerful oxidants nitrite, nitrate, a nd peroxynitrite. We hypothesized that increased oxidative stress may contr ibute to the pathogenesis of acute chest syndrome and measured F-2 isoprost anes, a nonenzymatically generated molecule resulting from free radical cat alyzed lipid peroxidation in patients with sickle cell disease in various s tages of disease. Plasma samples were obtained from nineteen patients with sickle cell disease during acute chest syndrome (pre- and postexchange tran sfusion), vasoocclusive crisis, and/or at baseline; 12 normal volunteers se rved as controls. F-2 isoprostanes were measured by gas chromatography/mass spectrophotometry. There was a 9-fold increase in F-2 isoprostanes in pati ents with acute chest syndrome as compared with normal volunteers. There wa s approximately a 50-60% decline in isoprostanes postexchange transfusion t o a level similar to that of patients with sickle cell disease at baseline. There was no difference in isoprostanes between vasoocclusive crisis and p atients with sickle cell disease at baseline. Increased oxidative stress, m easured by generation of F-2 isoprostanes, occurs during acute chest syndro me and may have an important role in the pathogenesis of this disease proce ss.