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

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.

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

“…Interestingly, in several in vivo studies, a high dose of NAC was found to act as a pro-oxidant rather than an antioxidant. High doses of NAC were found to be pro-oxidative in function in healthy rat striatum (48). Similarly, a low dose of NAC protected rats against endotoxin-mediated oxidative stress, whereas a high dose increased their mortality presumably because of its pro-oxidant action (49).…”

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

“…In addition, clozapine, olanzapine, and to a lesser extent risperidone, were able to reverse the changes induced by haloperidol (Pillai et al, 2007). Haloperidol-induced oxidative stress parameters in rats have also been shown to be ameliorated by the antioxidant drug, Nacetylcysteine (NAC) (Harvey et al, 2007). In-vitro cell studies have demonstrated a protective effect of atypicals, such as olanzapine and quetiapine, on PC12 cells exposed to oxidative stress Wei et al, 2003).…”

Oxidative Damage Compromises Energy Metabolism in the Axonal Degeneration Mouse Model of X-Adrenoleukodystrophy

“…We have previously reported that excess of VLCFA decreases reduced glutathione, and X-ALD cells are more sensitive to glutathione depletion (20). N-acetylcysteine was chosen, because it can regenerate reduced glutathione (GSH) and scavenge several ROS species including OH $ , H 2 O 2 , peroxyl radicals, and nitrogen-centered free radical (28). a-lipoic acid (LA) was chosen, as it can regenerate GSH from its oxidized counterpart (GS-SG) (3), thus enhancing the effects of NAC.…”