Erythrocytic Glutathione in Cystic Fibrosis: Conclusion

Jul-1-2014

Erythrocytic Glutathione in Cystic Fibrosis: ConclusionOxidants released on the surface of the bronchial epithelium by neutrophils and macrophages, represent a major component of the chronic airway inflammation of CF. Overcome by the large number of neutrophils present in the epithelial lining fluid (which may be as high as 100- to 1,000-fold that of normal subjects), the bronchial oxidant-antioxidant balance becomes disrupted. Canadian pharmacy levitra comments As a result, antioxidants like GSH become depleted, and antiproteases like ai-antitrypsin become unprotected against oxidative inactivation. The oxidation of antitrypsin by polymorphonucleated cells has been demonstrated in the sputum of patients with CF, leading to unopposed elastolytic destruction of the airways. Indeed, many of the pathologic changes observed in patients with CF are consistent with chronic uninhibited proteolysis and elastolysis.
The concentration of erythrocytic antioxidants, particularly the GSH system, has been extensively studied in patients with CF and found to be either increased or unchanged. To the best of our knowledge, however, no other studies have so far attempted a correlation between the concentration of RBC GSH and the extent of functional severity in patients with CF. The correlation demonstrated by our data could thus provide an explanation for the large interindividual variability of the GSH system activity. Patients with worse function (and possibly a greater oxidant burden) would be more likely to exhibit higher levels of RBC GSH than patients with mild dysfunction.
Our rationale for measuring only antioxidant concentrations and not the “oxidant burden” was based on the day-by-day variability of oxidative stress caused by recurrent infections and exacerbations. Indeed, the correlation reported by Meyer and Zimmerman between the intra-airway release of neutrophil proteases/pro-oxidants and the degree of pulmonary dysfunction of patients with CF was measured during periods of respiratory exacerbations. Thus, one baseline observation might not have accurately reflected the “cumulative” oxidative stress suffered by the airways of our patients. Moreover, because the measurement of intra-airway oxidants is technically cumbersome and requires a bronchoscopy, the assay would not have lent itself to a possible routine use. We hypothesized that antioxidant concentrations of peripheral erythrocytes might have provided a more accessible, albeit indirect, indicator for the “cumulative” damage suffered by patients with CF. Our data support this premise.
In summary, patients with CF having more severe respiratory dysfunction appear to have a compensatory increase in their intracellular RBC GSH concentration when compared to patients with CF having mild respiratory dysfunction and age-matched controls. Thus, there appears to be a compensatory, but probably inadequate, increase in erythrocytic antioxidants. Further evaluation of the role of RBC GSH as a “biologic marker” of CF severity could be carried out by comparing baseline concentrations with levels measured during intercurrent respiratory infections, antibiotic treatment, or aerosolized administration of GSH.