Effect of Chronic N-Acetyl Cysteine Administration on Oxidative Status in the Presence and Absence of Induced Oxidative Stress in Rat Striatum |
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Authors: | Brian H Harvey Charise Joubert Jan L du Preez Michael Berk |
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Institution: | (1) Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom Campus, Potchefstroom, South Africa;(2) University of Melbourne, Melbourne, VIC, Australia;(3) Mental Health Research Institute, Melbourne, VIC, Australia;(4) Orygen Youth Health, Parkville, VIC, Australia |
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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. |
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Keywords: | N-acetylcysteine Striatum Oxidative stress Haloperidol Neurodegenerative disorder |
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