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articles > copd & lung
disorders > a role for CFTR in the elevation of glutathione levels in
the lung by oral glutathione administration
Glutathione Articles - COPD
(Chronic Obstructive Pulmonary Disease) & Lung Disorders
A role for CFTR in the elevation of glutathione levels in the lung by oral
glutathione administration
Chirag Kariya, Heather Leitner, Elysia Min,
Christiaan van Heeckeren, Anna van Heeckeren, Brian J. Day
Am J Physiol Lung Cell Mol Physiol 292: L1590–L1597, 2007.
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The cystic fibrosis
transmembrane conductance regulator (CFTR) protein is the only known
apical glutathione (GSH) transporter in the lung. The purpose of these
studies was to determine whether oral GSH or glutathione disulfide
(GSSG) treatment could increase lung epithelial lining fluid (ELF) GSH
levels and whether CFTR plays a role in this process. The
pharmacokinetic profile of an oral bolus dose of GSH (300 mg/kg) was
determined in mice. Plasma, ELF, bronchoalveolar lavage (BAL) cells, and
lung tissue were analyzed for GSH content. There was a rapid elevation
in the GSH levels that peaked at 30 min in the plasma and 60 min in the
lung, ELF, and BAL cells after oral GSH dosing. Oral GSH treatment
produced a selective increase in the reduced and active form of GSH in
all lung compartments examined. Oral GSSG treatment (300 mg/kg) resulted
in a smaller increase of GSH levels. To evaluate the role of CFTR in
this process, Cftr knockout (KO)
mice and gut-corrected Cftr KO-transgenic (Tg) mice were given an oral
bolus dose of GSH (300 mg/kg) and compared with wild-type mice for
changes in GSH levels in plasma, lung, ELF, and BAL cells. There was a
twofold increase in plasma, a twofold increase in lung, a fivefold
increase in ELF, and a threefold increase in BAL cell GSH levels at 60
min in wild-type mice; however, GSH levels only increased by 40% in the
plasma, 60% in the lung, 50% in the ELF, and twofold in the BAL cells
within the gut-corrected Cftr KO-Tg mice. No change in GSH levels was
observed in the uncorrected Cftr KO mice. These studies suggest that
CFTR plays an important role in GSH uptake from the diet and transport
processes in the lung.
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