title: Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum.
abstract: Antioxidants have possible therapeutic value in neurodegenerative disorders, although they may have pro-oxidant effects under certain conditions. Glutathione (GSH) is a key free radical scavenger. N-acetylcysteine (NAC) bolsters GSH and intracellular cysteine and also has effective free radical scavenger properties. The effects of chronic NAC administration (50 mg/kg/day, 500 mg/kg/day, 1500 mg/kg/day x 21 days) on cellular markers of oxidative status was studied in striatum of healthy male Sprague-Dawley rats as well as in animals with apparent striatal oxidative stress following chronic haloperidol treatment (1.5 mg/kg/day x 3 weeks). In non-haloperidol treated animals, NAC 50 and 500 mg/kg did not affect oxidative status, although NAC 1,500 mg/kg significantly increased striatal superoxide levels, decreased lipid peroxidation and increased consumption of reduced glutathione (GSH). Haloperidol alone evoked a significant increase in superoxide and lipid peroxidation. All NAC doses blocked haloperidol induced increases in superoxide levels, while NAC 500 mg/kg and 1,500 mg/kg prevented haloperidol-associated lipid peroxidation levels and also increased the GSSG/GSH ratio. NAC may protect against conditions of striatal oxidative stress, although possible pro-oxidative actions at high doses in otherwise healthy individuals, e.g. to offset worsening of neurodegenerative illness, should be viewed with caution.
authors.affiliation: Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom Campus, Potchefstroom, South Africa. brian.harvey@nwu.ac.za
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
authors.forename: Charise
authors.initials: C
authors.lastname: Joubert
authors.forename: Jan L
authors.initials: JL
authors.lastname: du Preez
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006220:Haloperidol / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000517:prevention & control; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D016166:Free Radical Scavengers; D013481:Superoxides; D005978:Glutathione; D006220:Haloperidol; D000111:Acetylcysteine