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Neurochemical Research

, Volume 33, Issue 3, pp 508–517 | Cite as

Effect of Chronic N-Acetyl Cysteine Administration on Oxidative Status in the Presence and Absence of Induced Oxidative Stress in Rat Striatum

  • Brian H. Harvey
  • Charise Joubert
  • Jan L. du Preez
  • Michael Berk
Original Paper

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 × 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 × 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.

Keywords

N-acetylcysteine, Striatum, Oxidative stress Haloperidol Neurodegenerative disorder 

Notes

Acknowledgements

The authors would like to acknowledge the University of Melbourne (Barwon Health) for funding, Cor Bester and Antoinette Fick at the North-West University Animal Research Centre for the welfare of the animals, and Nico Liebenberg for his valuable assistance in the preparation of the manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Brian H. Harvey
    • 1
  • Charise Joubert
    • 1
  • Jan L. du Preez
    • 1
  • Michael Berk
    • 2
    • 3
    • 4
  1. 1.Unit for Drug Research and Development, School of Pharmacy (Pharmacology)North-West UniversityPotchefstroomSouth Africa
  2. 2.University of MelbourneMelbourneAustralia
  3. 3.Mental Health Research InstituteMelbourneAustralia
  4. 4.Orygen Youth HealthParkvilleAustralia

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