Toxic effects of the antihistamine cetirizine in mussel Mytilus galloprovincialis Miguel Teixeira a , ^ Angela Almeida b ,V ^ ania Calisto a , Valdemar I. Esteves a , Rudolf J. Schneider c , Frederick J. Wrona d , Amadeu M.V.M. Soares b , Etelvina Figueira b , Rosa Freitas b, * a Department of Chemistry & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal b Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal c BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str.11, Berlin, Germany d Department of Geography, University of Victoria, National Water Research Institute, STN CSC, Victoria, BC, Canada article info Article history: Received 28 October 2016 Received in revised form 4 January 2017 Accepted 14 February 2017 Keywords: Bivalves Biomarkers Oxidative stress Metabolic capacity Pharmaceuticals abstract Recent studies have become increasingly focused on the assessment of pharmaceuticals occurrence in aquatic ecosystems, however the potential toxicity to non-target organisms is still largely unknown. The antihistamine cetirizine is a commonly used pharmaceutical, already detected in surface waters of marine aquatic systems worldwide. In the present study Mytilus galloprovincialis mussels were exposed to a range of cetirizine concentrations (0.3, 3.0, 6.0 and 12.0 mg/L), resembling moderate to highly contaminated areas, over 28 days. The responses of different biochemical markers were evaluated in mussels whole soft tissue, and included energy-related parameters (glycogen content, GLY; protein content, PROT; electron transport system activity, ETS), and oxidative stress markers (superoxide dis- mutase activity, SOD; catalase activity, CAT; glutathione S-transferases activity, GSTs; lipid peroxidation levels, LPO; reduced (GSH) and oxidized (GSSG) glutathione content). The results obtained demonstrated that with the increase of exposure concentrations mussels tended to increase their energy reserves and maintain their metabolic potential, which was significantly higher only at the highest concentration. Our findings clearly revealed that cetirizine inhibited the activity of GSTs and although induced the activity of antioxidant enzymes (SOD and CAT) mussels were not able to prevent cellular damages observed through the increase of LPO associated to the increase of exposure concentrations. Thus, this study confirmed that cetirizine induces toxic effects in Mytilus galloprovincialis, which, considering their tro- phic relevance, wide use as bioindicator and wide spatial distribution of this species, can result in ecological and economic negative impacts at a large scale. © 2017 Elsevier Ltd. All rights reserved. 1. Introduction The increasing consumption of pharmaceuticals by an expo- nentially growing human population has resulted in ubiquity of these compounds in the environment (e.g. Fent et al., 2006; Kümmerer, 2010; Nikolaou et al., 2007; Puckowski et al., 2016). Furthermore, due to their incomplete removal in Wastewater Treatment Plants (WWTPs), which may only reach 10% for some substances, pharmaceuticals are continuously introduced into aquatic environment (Voulvoulis et al., 2016). This fact, associated to their environmental persistence, may explain the detected con- centrations of pharmaceuticals in the environment which range from ng L 1 to mgL 1 (for review see, Fent et al., 2006; Kümmerer, 2009; Santos et al., 2010). For these reasons, and because phar- maceuticals may preserve their biological activity in the environ- ment (Huerta et al., 2012) with potential impacts to aquatic wildlife, over the last years increasing attention has been given to under- stand the impacts of these contaminants in aquatic ecosystems, namely on the inhabiting organisms (among others, Aguirre- Martínez et al., 2013; Almeida et al., 2014; Canesi et al., 2007; Freitas et al., 2016, 2015a,b; Martin-Diaz et al., 2009a,b; Pires et al., 2016; Quinn et al., 2011). Several studies have demonstrated that different pharmaceuticals accumulate and cause toxic effects * Corresponding author. Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universit ario de Santiago, 3810-193 Aveiro, Portugal. E-mail address: rosafreitas@ua.pt (R. Freitas). Contents lists available at ScienceDirect Water Research journal homepage: www.elsevier.com/locate/watres http://dx.doi.org/10.1016/j.watres.2017.02.032 0043-1354/© 2017 Elsevier Ltd. All rights reserved. Water Research 114 (2017) 316e326