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Aquat Toxicol. 2018 May;198:10-19. doi: 10.1016/j.aquatox.2018.02.011. Epub 2018 Feb 19.

Effects of single and combined exposure of pharmaceutical drugs (carbamazepine and cetirizine) and a metal (cadmium) on the biochemical responses of R. philippinarum.

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Biology Department & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
Chemistry Department & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany.
Biology Department & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:


In the aquatic environment, organisms are exposed to complex mixtures of contaminants which may alter the toxicity profile of each compound, compared to its toxicity alone. Pharmaceutical drugs (e.g. carbamazepine (CBZ) and cetirizine (CTZ)) and metals (e.g. cadmium (Cd)) are among those contaminants that co-occur in the environment. However, most studies concerning their toxicity towards aquatic species are based on single exposure experiments. Thus, the present study aimed to evaluate single and combined effects of Cd and CBZ or CTZ (single conditions: Cd, CTZ, CBZ; combined conditions: CTZ + Cd, CBZ + Cd) on biomarkers related to oxidative stress and energy metabolism in the edible clam Ruditapes philippinarum, by exposing the organisms for 28 days to environmentally relevant concentrations of these contaminants. The biomarkers studied were: i) the electron transport system activity, protein and glycogen contents (indicators of organisms' metabolic status and energy reserves); ii) lipid peroxidation and the ratio between reduced and oxidized glutathione (indicators of oxidative stress); iii) superoxide dismutase and catalase activities (enzymes indicators of antioxidant defence) and iv) activity of glutathione S-transferases (family of enzymes indicators of biotransformation capacity). Results obtained showed that the uptake of Cd and CBZ was not affected by the combined presence of the contaminants. However, for CTZ, the uptake was higher in the presence than in the absence of Cd. Concerning toxicity data, in general, the combined exposures (CTZ + Cd, CBZ + Cd) had lower biological effects than the contaminants alone. Nevertheless, our data showed that despite the low concentrations tested, they were enough to exert biological effects that differed between single and combined treatments, evidencing the need to conduct more co-exposure studies to increase the environmental relevance of the gathered data.


Biomarkers; Invertebrates; Metals; Mixtures; Pharmaceutical drugs

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