Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum.
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.
Harvey
Brian H
BH
Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom Campus, Potchefstroom, South Africa. brian.harvey@nwu.ac.za
Joubert
Charise
C
du Preez
Jan L
JL
Berk
Michael
M
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
D014150:Antipsychotic Agents; D016166:Free Radical Scavengers; D013481:Superoxides; D005978:Glutathione; D006220:Haloperidol; D000111:Acetylcysteine