title: Effect of N-acetylcysteine on mitochondrial function following traumatic brain injury in rats.
abstract: Efficacy of N-acetylcysteine (NAC) in traumatic brain injury (TBI)-induced mitochondrial dysfunction was evaluated following controlled cortical impact injury in rats. Respiratory function and calcium transport of rat forebrain mitochondria from injured and uninjured hemispheres were examined. NAC significantly restored mitochondrial electron transfer, energy coupling capacity, calcium uptake activity and reduced calcium content absorbed to brain mitochondrial membranes when examined 12 h post-TBI if NAC was administered i.p. 5 min before injury or 30 min or 1 h postinjury. Glutathione (reduced form, GSH) levels in brain tissues were decreased at all time points examined over a 14-day observation period, while mitochondrial GSH levels significantly decreased only at 3 days and 14 days following TBI. NAC treatment given within 1 h greatly restored brain GSH levels from 1 h to 14 days and mitochondrial GSH levels from 12 h to 14 days post-TBI. NAC did not show protective effects when given 2 h postinjury. Our data indicate that NAC administered postinjury at an early stage can effectively restore TBI-induced mitochondrial dysfunction and the protective effect of NAC may be related to its restoration of GSH levels in the brain.
authors.affiliation: Department of Biochemistry, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: P L
authors.initials: PL
authors.lastname: Peterson
authors.forename: C P
authors.initials: CP
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016166:Free Radical Scavengers; D005978:Glutathione; D000111:Acetylcysteine