Oxidative Stress in Cystic Fibrosis: Does It Occur and Does It Matter?

Cystic fibrosis (CF) is a multiorgan system disease arising from a single biochemical abnormality in a protein encoded by a gene located on chromosome 7 (band q31-32). This protein (the cystic fibrosis transmembrane conductance regulator, CFTR) appears to couple ATP hydrolysis with transmembrane chloride (Cl-) conductance across apical epithelial surfaces under the control of CAMP-dependent proteinkinaseA regulation. The defect in CF impairs the normal movement of water and electrolytes across various epithelial surfaces, most notably in the respiratory tract (RT) but also in the pancreatohepatobililary system, the gastrointestinal tract, and the sweat excretion system. There is decreased C1- secretion and an increased sodium absorption, inadequate hydration of the respiratory tract secretions. This predisposes the CF patient to impaired mucociliary clearance, chronic lung infection, and bronchiectasis. The lung infection and the ensuing inflammatory-immune responses of the lung lead to the progressive lung destruction responsible for the pulmonary morbidity and mortality of CF. The infectious inflammatory-immune processes in the lungs of CF patients cause oxidative stress and related effects on the antiprotease/protease balance. This chapter discusses the evidence that oxidative stress occurs in CF and in the lung, and assesses whether oxidative stress contributes to the disease pathology and whether antioxidants might have useful therapeutic effects. There is speculation on the potential for antioxidant therapy and dilemma of administering aerosolized thiols or ascorbic acid. This chapter has focused on the roles that oxidative stress may contribute to the pathophysiology of CF, on how the balance between reactive oxidative species and nitrogen species may interact with biomolecular constituents at RT surfaces.