Central nervous system uptake of intranasal glutathione in Parkinson’s disease

Abstract

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.

Quantitation of in vivo brain glutathione conformers in cingulate cortex among age‐matched control, MCI, and AD patients using MEGA‐PRESS

“…The MEGA-PRESS pulse sequence, on the other hand, is a very selective and confirmatory method to detect GSH peak. Hence, in any in vivo GSH quantitation study, MEGA-PRESS sequence could be the method of choice of MRS (Mandal, Shukla, Tripathi, & Ersland, 2019;Mischley et al, 2016;Tumati et al, 2018).…”

Hydrogenized Water Effects on Protection of Brain Cells from Oxidative Stress and Glutamate Toxicity

“…Glutathione (GSH) is a key intracellular tripeptide thiol antioxidant that protects cells from free radical damage by providing reducing equivalents for the reduction of lipid hydroperoxides [9]. GSH depletion has been implicated in the pathogenesis of neurological diseases, particularly in Parkinson's disease (PD) [34,35]. In this assay, we evaluated the effectiveness of hydrogenized water in increasing the concentration of GSH in brain cells as a marker for antioxidant levels in neuronal cells [36].…”

“…The cells were treated with a series of culture media containing various concentrations of hydrogenized water for 24 hr prior to exposing to oxidative stress challenge, and GSH levels were determined as described in Materials and Methods. In this plot of GSH level (compared to an untreated control) versus hydrogen concentration the EC 50 was calculated to be 0.0196 mM H 2 GSH participates in numerous cellular functions, and thus it is a critical cellular molecule [35,36]. GSH levels are correlated with increased oxidative damage and are known to diminish with increased age and in certain disease states [37,38].…”

Preventing and Slowing the Progression of Parkinson's: A Clinical Conversation with Laurie Mischley, ND, MPH, PhD, and Robert Rountree, MD

“…In a third study, we used an MRI machine to measure baseline brain glutathione. 24 We then took a new scan every 10 minutes. There was a 240% increase in brain glutathione, in the putamen, after about 45 minutes.…”