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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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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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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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Correspondence to Brian H. Harvey.

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Harvey, B.H., Joubert, C., du Preez, J.L. et al. Effect of Chronic N-Acetyl Cysteine Administration on Oxidative Status in the Presence and Absence of Induced Oxidative Stress in Rat Striatum. Neurochem Res 33, 508–517 (2008). https://doi.org/10.1007/s11064-007-9466-y

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  • DOI: https://doi.org/10.1007/s11064-007-9466-y

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