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Glutathione Articles - Cystic Fibrosis
Cystic Fibrosis-Related Diabetes: From CFTR Dysfunction
to Oxidative Stress
Ntimbane T, Comte B, Mailhot G, Berthiaume Y,
Poitout V, Prentki M, Rabasa-Lhoret R, Levy E
Clin Biochem Rev Vol 30 November 2008
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ABSTRACT
Cystic fibrosis (CF) represents the most common lethal autosomal
recessive disorder in the Caucasian population. It is causedby mutations
in the CF transmembrane conductance regulator (CFTR) gene, resulting in
abnormal Na+ and Cl- transport in several tissues. Its main clinical
manifestations include bronchopulmonary infections along with
gastrointestinal and nutritional disorders. Intense and recurrent
inflammation ultimately leads to an overabundance of activated
neutrophils and macrophages that contribute to free radical generation.
Furthermore, CFTR defects directly affect glutathione transport and
homeostasis, while intestinal fat malabsorption limits uptake of
endogenous antioxidant vitamins. Collectively, these abnormal events
disturb the balance between pro- and anti-oxidants and promote oxidative
stress, which may play a significant role in CF-related diabetes (CFRD),
a severe complication associated with a drastic increase of morbidity
and mortality. This review will focus on the involvement of oxidative
stress in CF pathology, especially its role in the occurrence of CFRD.
The multiple abnormalities in the oxidant/antioxidant balance could be a
potential target for a new therapeutic approach.
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