The systemic availability of oral glutathione

Witschi, Anne; Reddy, S; Stofer, Bert E.; Lauterburg, Bernhard H.

doi:10.1007/bf02284971

Cited by 226 publications

(155 citation statements)

References 14 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…Oral supplementation of healthy volunteers with up to 3 g GSH did not alter plasma levels of cysteine or GSH [72], perhaps because the intestinal mucosal epithelia and liver have very high levels of GGT and the supplemented GSH was rapidly metabolized. The half-life of GSH in human plasma is less than 3 min [73].…”

Section: Human Studies Of Gsh Supplementationmentioning

confidence: 94%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Human Studies Of Gsh Supplementationmentioning

confidence: 94%

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

View full text Add to dashboard Cite

show abstract

“…Witschi et al administered a single oral dose of up to 3 g of GSH to seven healthy subjects and did not observe an increase in blood GSH levels, concluding ''it is not feasible to increase circulating GSH to a clinically beneficial extent by the oral administration of 3 g of GSH.'' 22 Yet three studies have evaluated the impact of reduced GSH supplementation combined with oxidative chemotherapeutic agents in patients with various cancers [23][24][25] ; all three trials demonstrated reduced adverse effects of the chemotherapy without negative effects on the effectiveness of the regimen, suggesting some physiologic effect from oral dosing. Unfortunately GSH status was not measured in any of these trials.…”

Section: Introductionmentioning

confidence: 99%

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

Allen

Bradley

2011

The Journal of Alternative and Complementary Medicine

136

View full text Add to dashboard Cite

Background: The tripeptide glutathione (GSH) is the most abundant free radical scavenger synthesized endogenously in humans. Increasing mechanistic, clinical, and epidemiological evidence demonstrates that GSH status is significant in acute and chronic diseases. Despite ease of delivery, little controlled clinical research data exist evaluating the effects of oral GSH supplementation. Objectives: The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers. Design: This was a randomized, double-blind, placebo-controlled clinical trial. Setting/location: The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA. Subjects: Forty (40) adult volunteers without acute or chronic disease participated in this study. Intervention: Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks. Outcome measures: Primary outcome measures included change in creatinine-standardized, urinary F2-isoprostanes (F2-isoP) and urinary 8-hydroxy-2¢-deoxyguanosine (8-OHdG). Changes in erythrocyte GSH concentrations, including total reduced glutathione (GSH), oxidized glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem liquid chromatography/mass spectrometry. Analysis of variance was used to evaluate differences between groups. Results: There were no differences in oxidative stress biomarkers between treatment groups at baseline. Thirtynine (39) participants completed the study per protocol. Changes in creatinine standardized F2-isoP (ng/mg creatinine) (0.0 -0.1 versus 0.0 -0.1, p = 0.38) and 8-OHdG (lg/g creatinine) (-0.2 -3.3 versus 1.0 -3.2, p = 0.27) were nonsignificant between groups at week 4. Total reduced, oxidized, and ratio measures of GSH status were also unchanged. Conclusions: No significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.

show abstract

“…19 Unfortunately, direct oral GSH administration does not result in significant systemic elevation of GSH levels because of intestinal and hepatic γ-GT. 20 The present study aims to evaluate a glutathione surrogate (Ψ-GSH; Figure 1) that could potentially substitute for GSH while possessing resistance to γ-GT mediated metabolism. It is expected that Ψ-GSH would be resistant to γ-GT by virtue of the substitution of the γ-glutamyl-cysteine amide with a urea isostere.…”

mentioning

confidence: 99%

Potential of a γ-Glutamyl-Transpeptidase-Stable Glutathione Analogue against Amyloid-β Toxicity

Vince

2012

ACS Chem. Neurosci.

View full text Add to dashboard Cite

The antioxidant properties of glutathione (GSH) and their relevance to oxidative stress induced pathological states such as Alzheimer's disease is well-established. The utility of GSH itself as a pharmacotherapeutic agent for such disorders is limited because of the former's lability to breakdown through amide cleavage by the ubiquitous enzyme γ-glutamyl transpeptidase (γ-GT). In the present study, a GSH analogue, Ψ-GSH, where the γ-glutamylcysteine amide linkage is replaced with a ureide linkage, was synthesized. Ψ-GSH was found to be stable toward γ-GT mediated breakdown. Ψ-GSH fulfilled four cardinal properties of GSH, namely, traversing across the blood brain barrier (BBB) via the GSH active uptake machinery, replacing GSH in the glyoxalase-I mediated detoxification of methylglyoxal, protecting cells against chemical oxidative insult, and finally lowering the cytotoxicity of amyloid-β peptide. These results validate Ψ-GSH as a viable metabolically stable replacement for GSH and establish it as a potential preclinical candidate for treatment of oxidative stress mediated pathology.

show abstract

The systemic availability of oral glutathione

Cited by 226 publications

References 14 publications

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

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

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

Potential of a γ-Glutamyl-Transpeptidase-Stable Glutathione Analogue against Amyloid-β Toxicity

Contact Info

Product

Resources

About