Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum

Neurochem Res. 2008 Mar;33(3):508-17. doi: 10.1007/s11064-007-9466-y. Epub 2007 Aug 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Antipsychotic Agents / toxicity
  • Dose-Response Relationship, Drug
  • Free Radical Scavengers / pharmacology*
  • Glutathione / metabolism
  • Haloperidol / toxicity
  • Lipid Peroxidation / drug effects
  • Male
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Neostriatum / pathology
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / prevention & control
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxides / metabolism

Substances

  • Antipsychotic Agents
  • Free Radical Scavengers
  • Superoxides
  • Glutathione
  • Haloperidol
  • Acetylcysteine