Toxicology Letters 194 (2010) 1–7 Contents lists available at ScienceDirect Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet Behavioral effects and oxidative status in brain regions of adult rats exposed to BDE-99 Montserrat Bellés a,b,∗ , Virginia Alonso a,b , Victoria Linares a,b , Maria L. Albina a,b , Juan J. Sirvent c , José L. Domingo a , Domènec J. Sánchez a,b a Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV “Universitat Rovira i Virgili”, Sant Llorens 21, 43201 Reus, Catalonia, Spain b Physiology Unit, School of Medicine, IISPV “Universitat Rovira i Virgili”, Sant Llorens 21, 43201 Reus, Catalonia, Spain c Pathology Unit, School of Medicine, IISPV “Universitat Rovira i Virgili”, Sant Llorens 21, 43201 Reus, Catalonia, Spain article info Article history: Received 27 November 2009 Received in revised form 12 January 2010 Accepted 14 January 2010 Available online 22 January 2010 Keywords: BDE-99 Adult rats Oxidative stress (OS) Neurotoxicity Brain abstract Polybrominated diphenyl ethers (PBDEs) are used as flame retardants. Although developmental neu- rotoxicity of PBDEs has been already investigated, little is still known about their potential neurotoxic effects in adulthood. In this study, we assessed the oxidative damage in brain sections and the possible behavioral effects induced by exposure to 2,2 ′ ,4,4 ′ ,5-pentabromodiphenyl ether (BDE-99). Adult male rats (10/group) received BDE-99 by gavage at single doses of 0, 0.6 or 1.2 mg/kg/body weight. Forty-five days after exposure, the following behavioral tests were conducted: open-field activity, passive avoidance and Morris water maze. Moreover, cortex, hippocampus and cerebellum were processed to examine the following oxidative stress (OS) markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS). In cerebellum, BDE- 99 significantly decreased SOD, CAT and GR activities at the highest BDE-99 dose. A decrease in CAT and SOD activities was also observed in cortex and hippocampus, respectively. In the behavioral tests, no BDE-99 effects were observed, while histopathological examination of the brain regions was normal. The current results show that the brain antioxidant capacity is affected by BDE-99 exposure, mainly in cerebellum. Oxidative damage could be a mechanism for BDE-99 neurotoxicity in adult rats. © 2010 Published by Elsevier Ireland Ltd. 1. Introduction Brominated flame retardants are a diverse group of industrial compounds used to retard, suppress or inhibit combustion pro- cesses to reduce fire risks (IPCS, 1994). Polybrominated diphenyl ethers (PBDEs), used as additive flame retardants, have the chemi- cal formula C 12 H (0–9) Br (1–10) O, being 209 the theoretical number of possible congeners is 209. Products that contain PBDEs are textiles, building materials, as well as a wide variety of electrical and elec- tronic appliances, including cases for television sets and computers (Branchi et al., 2003; Birnbaum and Staskal, 2004). The chemical characteristics and some toxicological properties of PBDEs are comparatively similar to those of polychlorinated biphenyls (PCBs) (Kodavanti and Ward, 2005; Coburn et al., 2007). Like PCBs, they are persistent organic pollutants and bioaccumu- late in the environment (Schecter et al., 2005; Law et al., 2006). ∗ Corresponding author at: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV “Universitat Rovira i Virgili”, Sant Llorens 21, 43201 Reus, Catalonia, Spain. Tel.: +34 977 759374; fax: +34 977 759322. E-mail address: montserrat.belles@urv.cat (M. Bellés). A number of studies have indicated the presence of PBDEs in sedi- ments, soil, outdoor and indoor air, house dust, foods, birds, fish and marine and terrestrial animals (Darneurd et al., 2001; De Wit, 2002; Bocio et al., 2003; Domingo, 2004). Furthermore, human levels of PBDEs have been detected in adipose tissue, serum and breast milk (Costa and Giordano, 2007). In contrast to PCBs, dioxins and furans, whose concentrations in human tissues and breast milk have been declining in the past 20 years, levels of PBDEs have been increas- ing (Meneses et al., 1999; Schecter et al., 2005; Schuhmacher et al., 2007, 2009). One of the PBDE congeners most frequently found in the environment is the 2,2 ′ ,4,4 ′ ,5-pentabromodiphenyl ether (BDE- 99) (McDonald, 2002; Viberg et al., 2006; Lundgren et al., 2009). In particular, this congener is the most commonly found in human milk and cord blood (Norén and Meironyté, 2000; Schuhmacher et al., 2009). During development, mammals may be exposed to toxicants either as fetuses via maternal intake, during the newborn period via intake of breast milk, or by direct ingestion or contact with toxicants (Viberg et al., 2006). A number of experimental studies in mice and rats indicate that PBDEs can cause developmen- tal neurotoxic effects (Costa and Giordano, 2007; Fischer et al., 2008; Cheng et al., 2009). Kuriyama et al. (2005) showed that 0378-4274/$ – see front matter © 2010 Published by Elsevier Ireland Ltd. doi:10.1016/j.toxlet.2010.01.010