title: 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.
authors.affiliation: Center for Orphan Drug Research, Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. holma101@umn.edu
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Holmay
authors.forename: Melissa
authors.initials: M
authors.lastname: Terpstra
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Coles
authors.forename: Usha
authors.initials: U
authors.lastname: Mishra
authors.forename: Matthew
authors.initials: M
authors.lastname: Ahlskog
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
authors.forename: James C
authors.initials: JC
authors.lastname: Cloyd
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tuite
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000293:Adolescent; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D000978:Antiparkinson Agents; D005978:Glutathione; D000111:Acetylcysteine