A Pilot Study of the Effect of Inhaled Buffered Reduced Glutathione on the Clinical Status of Patients With Cystic Fibrosis

Bishop, Clark T.; Hudson, Valerie M.; Hilton, Sterling C.; Wilde, Cathleen

doi:10.1378/chest.127.1.308

Cited by 76 publications

(89 citation statements)

References 45 publications

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“…N-acetyl cysteine did not increase the GSH concentrations significantly in the plasma or in the lung compartment of chronic obstructive pulmonary disorder patients compared with controls even at the high dose of 600 mg three times daily for 5 days (7). Attempts have also been made to increase the ELF GSH by means of aerosol delivery (3,4,9,22,27,44), intravenous administration (9,30), and oral administration of GSH (2,18,55). Inhalation of GSH increased the ELF GSH levels, but it also increased the levels of GSSG (44).…”

Section: Discussionmentioning

confidence: 99%

A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration

Kariya¹,

Leitner²,

Min³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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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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Section: Discussionmentioning

confidence: 99%

A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration

Kariya¹,

Leitner²,

Min³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This treatment also reduced superoxide production by inflammatory cells (Roum et al 1993). However, subjects treated with inhaled glutathione had no detectable change in BAL markers of oxidative stress (Bishop et al 2005;Hartl 2005). Inhaled glutathione therapy for CF has attracted much attention, but its therapeutic benefit has not been adequately studied.…”

Section: Modulators Of Intracellular Signalingmentioning

confidence: 96%

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

Chmiel

Konstan

Elborn

2013

Cold Spring Harbor Perspectives in Medicine

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“…To explore the potential usefulness of GSH aerosolization therapy, a trial was conducted using an over-the-counter preparation of GSH (pH 5.2; 66 mg/kg body weight divided into 4 inhalation sessions per day) for 8 weeks in 19 volunteers with CF, aged 6 to 19 [88]. The volunteers were assigned to either placebo or GSH, with 10 people in the GSH group.…”

Section: Human Studies Of Gsh Supplementationmentioning

confidence: 99%

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Cantin

White

Cross

et al. 2007

Free Radical Biology and Medicine

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Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed. IntroductionCystic fibrosis (CF) is the most common fatal disease caused by a single gene defect in Europe and North America [1,2]. The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands ☆ A list of participants may be found in the Acknowledgments.

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A Pilot Study of the Effect of Inhaled Buffered Reduced Glutathione on the Clinical Status of Patients With Cystic Fibrosis

Cited by 76 publications

References 45 publications

A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration

A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

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