N-Acetylcysteine Attenuates Copper Overload-Induced Oxidative Injury in Brain of Rat Dervis Özcelik & Hafize Uzun & Mustafa Nazıroglu Received: 24 October 2011 / Accepted: 2 January 2012 / Published online: 13 January 2012 # Springer Science+Business Media, LLC 2012 Abstract Copper is an integral part of many important enzymes involved in a number of vital biological processes. Even though it is essential to life, at elevated tissue concen- trations, copper can become toxic to cells. Recent studies have reported oxidative damage due to copper in various tissues. Considering the vulnerability of the brain to oxidative stress, this study was undertaken to explore possible beneficial anti- oxidant effects of N-acetylcysteine on oxidative stress induced by copper overload in brain tissue of rats. Thirty-two Wistar rats were equally divided into four groups. The first group was used as control. The second, third, and fourth groups were given 1 g/L copper in their drinking water for 1 month. At the end of this period, the group 2 rats were sacrificed. During the next 2 weeks, the rats in group 3 were injected intraperito- neally with physiological saline and those in group 4 with 20 mg/kg intraperitoneal injections of N-acetylcysteine. In group 2 the lipid peroxidation and nitric oxide levels were increased in the brain cortex while the activities of superoxide dismutase and catalase and the concentration of glutathione were decreased. In rats treated with N-acetylcysteine, lipid peroxidation decreased and the activities of antioxidant en- zyme improved in the brain cortex. In conclusion, treatment with N-acetylcysteine modulated the antioxidant redox system and reduced brain oxidative stress induced by copper. Keywords N-Acetylcysteine . Oxidative defense . Lipid peroxidation . Brain . Copper toxicity Introduction Copper (Cu) is an essential trace metal in living organisms. A great number of biologically active centers contain Cu. It is absorbed from the diet through the small intestine, prob- ably as chelates with amino acids such as histidine, methi- onine, and cysteine or with small peptides. Still in bound form, Cu reaches the liver, where it may be stored within hepatocytes, secreted into plasma, or excreted in bile [1]. At least 90% of total plasma Cu occurs in ceruloplasmin, and the rest is bound to albumin, amino acids, or small peptides. In some abnormal conditions, such as Wilson’ s disease and liver failure, there is an excessive accumulation of Cu in plasma [2]. So, in addition to brain and liver, excess Cu can also affect blood cells. Different tissues have differ- ent susceptibilities to oxidative stress [3]. Copper is also implicated in the etiology of various neurodegenerative disorders [4]. The central nervous system is particularly sensitive to this kind of damage for a number of reasons, including a low level of some antioxidant enzymes, a high content of easily oxidized substrates (e.g., membrane polyunsaturated lipids), and an inherently high flux of reactive oxygen species (ROS) generated during neurochemical reactions [5, 6]. Previous studies have shown that Cu overload readily leads to oxidative stress, due to redox cycling [1, 7]. Although the D. Özcelik (*) Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University, TR-34303, Cerrahpasa, Istanbul, Turkey e-mail: dozcelik@istanbul.edu.tr H. Uzun Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey M. Nazıroglu Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey Biol Trace Elem Res (2012) 147:292–298 DOI 10.1007/s12011-012-9320-1