N-Acetyl-L-cysteine, a low-molecular weight thiol compound, with two different doses was used to prevent fenthion, an organophosphorus insecticide and acaricide, related oxidative stress in the brain of a model organism, Cyprinus carpio. Fish were exposed to sub-lethal and nominal concentration of fenthion after intraperitoneal injection of 0.5 or 400 mg/kg NAC. Brain tissues were then dissected and homogenized to analyse GSH, GSSG, TBARS, and protein contents. Enzymes that constitute the first line antioxidant defence, namely SOD and CAT, GSH-related enzymes, GR and GST, together with AChE activities were also determined spectrophotometrically. Fenthion did not cause any alteration in SOD and CAT activities while increasing GSH content, GSH/GSSG ratio and GST specific enzyme activity and decreasing GSSG, TBARS, and protein contents. Although, the highest induction in SOD and GST enzymes activities and the highest increase in GSH content were observed in the 0.5 mg/kg NAC-injected fish, their protein contents showed a decrease. 400 mg/kg NAC impeded the activation of the GST enzyme and a higher decrease in lipid peroxidation was observed. Fish were also protected against protein depletion by the higher dose NAC application. AChE activity was not influenced by fenthion exposure. Xenobiotic and GSH transporters may cause mild oxidative stress conditions in brain. Cellular redox status could trigger a series of reactions that result in an increase in SOD activity and a decrease in protein content. Based on the present results, it was suggested that the usefulness of NAC against fenthion depends on applied dose and tissue characteristics. Species-specifity and concentration selection should be taken into consideration in studies dealing with anticholinesterases. (C) 2009 Elsevier Inc. All rights reserved.