QUARTERLY Communication Antioxidant status in erythrocytes of cystic fibrosis children

Activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes of cystic fibrosis children were studied in order to estimate the severity of their deficiency. Our results point to increased susceptibility of erythrocytes of cystic fibrosis subjects to oxidative injury and indicate that the antioxidant status of patients should be carefully monitored.

Cystic fibrosis (CF) is the most frequent genetic disease affecting Caucasian populations.In cystic fibrosis, as a result of chronic pulmonary infections and digestive malabsorption, an imbalance between the production of reactive oxygen species and their inactivation by protective systems is observed [1,2].It is commonly accepted that some plasma as well as erythrocyte biomarkers serve for the evaluation involved in the total antioxidant capacity of blood.Several studies demonstrated lower values of total radical-trapping antioxidants parameters (TRAP) in CF patients than in healthy subjects, the lower values being accompanied by low concentration of vitamin E, A and b-carotene in plasma [3,4].Only a few informations are available on antioxidants in erythrocytes of children with cystic fibrosis.A low level of vitamin E was previously reported by Peters & Kelly [5] and Laskowska-Klita et al. [6].Studies of Benabdeslam et al. [4] and Niki et al. [7] indicated that oxidation processes in erythrocytes and their membranes due to oxidative stress may result in haemolysis.Therefore some markers of the antioxidant defence system of red blood cells were studied to estimate its deficiency in the population of CF children treated at our Institute.
Mother and Child, aged between 1 and 18 years were divided into two groups: PS -patients with pancreatic sufficiency (n = 13) and PIS -patients with pancreatic insufficiency (n = 87).Patients were classified according to clinical symptoms and genetic and biochemical parameters.Twenty five healthy children in the same age range were selected as control subjects.The institutional review board has approved the studies.Informed consent was obtained from parents.

RESULTS
The concentration of vitamin E in erythrocytes of CF patients was half that found in healthy children (2.9 mmol/L).It amounted to 1.36 mmol/L and 1.74 mmol/L in the PIS and PS group, respectively (P < 0.0001).These results indicate that the deficiency of vitamin E in CF patients especially those with PIS are at the level of risk of oxidative injury to lipophilic cell fractions (Fig. 1).Among antioxidant enzymatic activities in RBC, that of GPx remained unaffected.Catalase activity was lower in the PS and PIS groups than in control.Activity of SOD was higher both in PIS group and in PS group as compared with the control.The differences were significant at a level of 0.0001 and 0.01, respectively (Table 1).

DISCUSSION
It is well known that CF patients, due to impaired ability to absorb fat from the gastrointesti-  nal tract, show a tendency to have vitamin E deficiency [1].The content of vitamin E in plasma represents a small fraction of this vitamin, which is known to be located mainly in the cell membrane.Vitamin E as an antioxidant protects the lipid fraction of cell membrane from a free radical oxidative injury.Since it has been suggested that erythrocytes with lowered vitamin E concentration have a shortened survival time [10], red blood cells of CF patients are especially at the risk of oxidative damage.Low level of vitamin E in erythrocytes of CF patients was found by Peters & Kelly [5].We have confirmed their observation.Literature data concerning the activities of enzymatic antioxidants in RBC of CF patients are contradictory.Matkovics et al. [11] reported a significantly higher activity of SOD and catalase, but no modification of these enzymes was observed by Carmagnol et al. [12].In our CF patients SOD activity in erythrocytes was significantly higher (P < 0.0001), but that of catalase was significantly lower (P < 0.001) than in controls.Similarly to our findings, only slightly decreased GPx activity in erythrocytes of CF children was observed by Portal et al. [13] and Winklhofer-Roob [3].
Oxidant-antioxidant imbalance of erythrocytes in cystic fibrosis suggested previously by Benabdeslam et al. [4], Sokol et al. [14] and Brown & Kelly [2] was confirmed in our studies.
Elevated SOD activity, may expresses an adaptive response of RBC to excess of superoxide anion in erythrocytes of CF patients.Dismutation of this radical to hydrogen peroxide gives the substrate for GPx and catalase.Activities of these enzymes at the level observed in this study seem to be insufficient to neutralize H 2 O 2 -and oxygen radicals.
The obtained results point to increased susceptibility of erythrocytes of CF children to oxidative injury and indicate that the antioxidant status of patients should be carefully monitored to consider if necessary application of some antioxidant therapy.

Figure 1 .
Figure 1.Concentration of vitamin E (mmol/L) in erythrocytes of control group and cystic fibrosis patients (for details see Methods).