N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases

Abstract

Objective: This study aimed to determine if the antioxidant N-acetylcysteine (NAC) is able to alter peripheral and central redox capabilities in patients with Parkinson disease (PD) or Gaucher disease (GD).

Methods: The study included nondemented adult subjects: 3 with PD, 3 with GD, and 3 healthy controls. Baseline brain glutathione (GSH) concentrations were measured using 7-T magnetic resonance spectroscopy (MRS). Baseline blood reduced-to-oxidized GSH ratios were determined for each subject. Brain GSH concentrations and blood redox ratios were then determined during and at specified time points after a single, 150-mg/kg NAC infusion.

Results: N-acetylcysteine increased blood GSH redox ratios in those with PD and GD and healthy controls, which was followed by an increase in brain GSH concentrations in all subjects.

Conclusions: This is the first demonstration that with MRS, it is possible to directly measure and monitor increases in brain GSH levels in the human brain in response to a single, intravenous administration of NAC. This work shows the potential utility of MRS monitoring, which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for PD disease, GD, and other neurodegenerative disorders.

Trial registration: ClinicalTrials.gov NCT01427517.

Figures

Figure 1

Blood GSH redox ratio (open squares) and brain GSH concentrations (closed circles) in PD, GD and healthy control subjects. Blood GSH redox ratios for HC 01 and HC02 not shown, due to difficulty with GSH/GSSG stabilization prior to bioanalysis.