Oxidative stress and antioxidant therapy in cystic fibrosis

Francesco Galli, Andrea Battistoni, Roberto Gambari, Alfonso Pompella, Alessandra Bragonzi, Francesca Pilolli, Luigi Iuliano, Marta Piroddi, Maria Cristina Dechecchi, Giulio Cabrini

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Cystic fibrosis is a lethal autosomal recessive condition caused by a defect of the transmembrane conductance regulator gene that has a key role in cell homeostasis. A dysfunctional cystic fibrosis transmembrane conductance regulator impairs the efflux of cell anions such as chloride and bicarbonate, and also that of other solutes such as reduced glutathione. This defect produces an increased viscosity of secretions together with other metabolic defects of epithelia that ultimately promote the obstruction and fibrosis of organs. Recurrent pulmonary infections and respiratory dysfunction are main clinical consequences of these pathogenetic events, followed by pancreatic and liver insufficiency, diabetes, protein-energy malnutrition, etc. This complex comorbidity is associated with the extensive injury of different biomolecular targets by reactive oxygen species, which is the biochemical hallmark of oxidative stress. These biological lesions are particularly pronounced in the lung, in which the extent of oxidative markers parallels that of inflammatory markers between chronic events and acute exacerbations along the progression of the disease. Herein, an abnormal flux of reactive oxygen species is present by the sustained activation of neutrophils and other cystic fibrosis-derived defects in the homeostatic processes of pulmonary epithelia and lining fluids. A sub-optimal antioxidant protection is believed to represent a main contributor to oxidative stress and to the poor control of immuno-inflammatory pathways in these patients. Observed defects include an impaired reduced glutathione metabolism and lowered intake and absorption of fat-soluble antioxidants (vitamin E, carotenoids, coenzyme Q-10, some polyunsaturated fatty acids, etc.) and oligoelements (such as Se, Cu and Zn) that are involved in reactive oxygen species detoxification by means of enzymatic defenses. Oral supplements and aerosolized formulations of thiols have been used in the antioxidant therapy of this inherited disease with the main aim of reducing the extent of oxidative lesions and the rate of lung deterioration. Despite positive effects on laboratory end points, poor evidence was obtained on the side of clinical outcome so far. These aspects examined in this critical review of the literature clearly suggest that further and more rigorous trials are needed together with new generations of pharmacological tools to a more effective antioxidant and anti-inflammatory therapy of cystic fibrosis patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Original languageEnglish
Pages (from-to)690-713
Number of pages24
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint

Cystic Fibrosis
Oxidative Stress
Antioxidants
Reactive Oxygen Species
Lung
Glutathione
Therapeutics
Epithelium
Hepatic Insufficiency
Exocrine Pancreatic Insufficiency
Protein-Energy Malnutrition
Cystic Fibrosis Transmembrane Conductance Regulator
Neutrophil Activation
Ubiquinone
Carotenoids
Regulator Genes
Bicarbonates
Unsaturated Fatty Acids
Vitamin E
Sulfhydryl Compounds

Keywords

  • Antioxidant
  • Cystic fibrosis
  • Glutathione
  • Inflammation
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Oxidative stress and antioxidant therapy in cystic fibrosis. / Galli, Francesco; Battistoni, Andrea; Gambari, Roberto; Pompella, Alfonso; Bragonzi, Alessandra; Pilolli, Francesca; Iuliano, Luigi; Piroddi, Marta; Dechecchi, Maria Cristina; Cabrini, Giulio.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1822, No. 5, 05.2012, p. 690-713.

Research output: Contribution to journalArticle

Galli, F, Battistoni, A, Gambari, R, Pompella, A, Bragonzi, A, Pilolli, F, Iuliano, L, Piroddi, M, Dechecchi, MC & Cabrini, G 2012, 'Oxidative stress and antioxidant therapy in cystic fibrosis', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1822, no. 5, pp. 690-713. https://doi.org/10.1016/j.bbadis.2011.12.012
Galli, Francesco ; Battistoni, Andrea ; Gambari, Roberto ; Pompella, Alfonso ; Bragonzi, Alessandra ; Pilolli, Francesca ; Iuliano, Luigi ; Piroddi, Marta ; Dechecchi, Maria Cristina ; Cabrini, Giulio. / Oxidative stress and antioxidant therapy in cystic fibrosis. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2012 ; Vol. 1822, No. 5. pp. 690-713.
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