EVIDENCE FOR INCREASED OXIDATIVE DAMAGE IN PATIENTS WITH CYSTIC-FIBROSIS

Patients with cystic fibrosis (CF) may be more susceptible to oxidative cell injury than normal healthy children due to both the impaired absorption of antioxidant nutrients and the increased oxidative stress caused by chronic pulmonary infections. The purpose of this study was to examine whether markers of oxidative damage to lipids (malondialdehyde-like substances and lipid hydroperoxides) and proteins (protein carbonyls) were present in the plasma of CF patients. Mean values (+/- SD) of thiobarbituric acid-reactive substances were significantly higher in patients (6.93 +/- 1.47 mu mol/L; n = 25) than in controls (5.84 +/- 0.59 mu mol/L; n = 10). FFA hydroperoxides were not detected in control subjects (the detection limit of the assay was 0.02 mu mol/L), but in 11 of the 33 CF patients studied they were found in a range of 0.03-0.34 mu mol/L. Plasma protein carbonyl concentrations did not differ significantly between the two groups (p = 0.076), although a much wider distribution was observed in the CF patients (range 0.17-5.64 nmol/mg protein) than in the control group (range 0.24-1.55 nmol/mg protein). No correlation was found between thiobarbituric acid-reactive substances and FFA hydroperoxides or between either of these markers and protein carbonyl content. Concentrations of plasma vitamin E, vitamin C, and protein sulfhydryls were within the normal ranges in both control subjects and CF patients. The concentration of uric acid was significantly reduced (p < 0.01) in the CF group (204 +/- 96.99 mu mol/L) compared with that in control subjects (352 +/- 81.11 mu mol/L), but reduction in plasma levels of this antioxidant did not correlate with increased markers of free radical damage. These results indicate that certain CF patients are more susceptible to oxidative damage, even in the presence of relatively normal concentrations of the major plasma antioxidants; these patients may benefit from increased antioxidant consumption.