Central nervous system uptake of intranasal glutathione in Parkinson's disease.

Autor:	Mischley LK; Department of Radiology, University of Washington (UW), Seattle, WA, USA.; Graduate Program in Nutritional Sciences, School of Public Health, University of Washington, Seattle, WA, USA.; School of Naturopathic Medicine, Bastyr University Research Institute, Kenmore, WA, USA., Conley KE; Department of Radiology, University of Washington (UW), Seattle, WA, USA., Shankland EG; Department of Radiology, University of Washington (UW), Seattle, WA, USA., Kavanagh TJ; Department of Environmental & Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA., Rosenfeld ME; Graduate Program in Nutritional Sciences, School of Public Health, University of Washington, Seattle, WA, USA.; Department of Environmental & Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA., Duda JE; Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., White CC; Department of Environmental & Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA., Wilbur TK; Department of Radiology, University of Washington (UW), Seattle, WA, USA., De La Torre PU; Department of Radiology, University of Washington (UW), Seattle, WA, USA.; School of Naturopathic Medicine, Bastyr University Research Institute, Kenmore, WA, USA., Padowski JM; Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA.; Department of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA, USA.
Jazyk:	angličtina
Zdroj:	NPJ Parkinson's disease [NPJ Parkinsons Dis] 2016 Feb 25; Vol. 2, pp. 16002. Date of Electronic Publication: 2016 Feb 25 (Print Publication: 2016).
DOI:	10.1038/npjparkd.2016.2
Abstrakt:	Glutathione (GSH) is depleted early in the course of Parkinson's disease (PD), and deficiency has been shown to perpetuate oxidative stress, mitochondrial dysfunction, impaired autophagy, and cell death. GSH repletion has been proposed as a therapeutic intervention. The objective of this study was to evaluate whether intranasally administered reduced GSH, (in)GSH, is capable of augmenting central nervous system GSH concentrations, as determined by magnetic resonance spectroscopy in 15 participants with mid-stage PD. After baseline GSH measurement, 200 mg (in)GSH was self-administered inside the scanner without repositioning, then serial GSH levels were obtained over ~1 h. Statistical significance was determined by one-way repeated measures analysis of variance. Overall, (in)GSH increased brain GSH relative to baseline ( P <0.001). There was no increase in GSH 8 min after administration, although it was significantly higher than baseline at all of the remaining time points ( P <0.01). This study is the first to demonstrate that intranasal administration of GSH elevates brain GSH levels. This increase persists at least 1 h in subjects with PD. Further dose-response and steady-state administration studies will be required to optimize the dosing schedule for future trials to evaluate therapeutic efficacy. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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