Chronic toxicity of the antiepileptic carbamazepine on the clam Ruditapes philippinarum

Abstract

The impacts of carbamazepine (CBZ) on aquatic organisms are yet not well investigated. The present study aimed to better understand the chronic effects of environmentally relevant concentrations of CBZ. The experiment was performed by exposing the filter feeding clam Ruditapes philippinarum to 0.00, 0.03, 0.30, 3.00 and 9.00 μg/L, during 28 days. To assess the chronic toxicity of the drug a battery of biomarkers related with health status and oxidative stress was applied. In order to quantify CBZ in the clam's tissues and in water samples ELISA was used. The present study showed three types of responses on the clams after a chronic exposure to CBZ. For control condition and the lower concentrations (0.03 and 0.30 μg/L) a "similar" metabolic state was observed and the most efficient antioxidant status leading to the elimination of reactive oxygen species formed during the metabolism of CBZ. The concentration of 3.00 μg/L seemed to be a "threshold" concentration, beyond which the concentration levels of CBZ began to exert a toxic effect, compromising the activity of biotransformation and antioxidant enzymes, with notorious effects at the highest CBZ concentration (9.00 μg/L). CBZ also seemed to alter the energy-related responses, especially the glycogen and electron system responses, revealing a slowdown in metabolism at the higher exposure concentrations (3.00 and 9.00 μg/L). Overall, the present study demonstrated that the higher CBZ concentrations can lead to the impairment of antioxidant enzymes compromising the neutralization of reactive oxygen species, and thus the ability to cope with oxidative stress.

General stress, detoxification pathways, neurotoxicity and genotoxicity evaluated in Ruditapes philippinarum exposed to human pharmaceuticals

“…These results are in agreement with those indicating significant induction in hepatopancreas tissues of Carcinus maenas when exposed to these drugs at 50 μg L À 1 , and are in concordance with the significant induction of GST activity by ibuprofen at 5 μg L À 1 (Aguirre- Martínez et al, 2013cMartínez et al, , 2013d. Similarly, Almeida et al (2015) reported significant induction of GST activity in soft tissues from R. philippinarum exposed to carbamazepine at 3 μg L À 1 . Results from the present study are in disagreement with those indicating activation of GST activity in digestive gland tissues of M. galloprovincialis when exposed to carbamazepine 0.1-10 μg L À 1 (Martín-Díaz et al, 2009b).…”

“…A significant increase on EROD activity was observed in R. philippinarum after exposure to caffeine, ibuprofen, carbamazepine and novobiocin increasing concentrations. This response was in accordance with previous work, indicating a significant increase after exposure to these drugs at the same concentrations in digestive gland tissues of C. fluminea after being exposed 21 days to these drugs (Aguirre-Martínez et al, 2015a, 2015b; A significant increase of CYP3A4 activity has been demonstrated in soft tissues from R. philippinarum exposed to carbamazepine at 0.03, 0.3, 3 and 9 μg L À 1 during 28 days, evidencing a higher capacity to metabolize this compound (Almeida et al, 2015). Induction of EROD activity has also been reported in digestive glands of E. complanata injected with an effluent extract containing pharmaceutical products (Martín-Díaz et al, 2009b); this is in line with experiments demonstrating that significant rise on EROD activity in D. polymorpha after exposure to organic contaminants (Binelli et al, 2005(Binelli et al, , 2006.…”

“…Similarly, a significant increase in LPO was shown after an injection of caffeine into digestive gland tissues of E. complanata (Martín-Díaz et al, 2009a) and in D. polymorpha after injection of 1 and 1.000 mg L À 1 of gemfibrozil and diclofenac into the posterior adductor muscle (Quinn et al, 2011). In contrast, low levels of LPO recorded in V. decussata exposed 96 h to carbamazepine (0.3-9 mg L À 1 ) (Almeida et al, 2014) and in R. philippinarum exposed 28 days to similar concentrations of carbamazepine (Almeida et al, 2015) might be a consequence of an increased antioxidant activity, suggesting effectiveness in combatting oxidative stress. Similarly in a trophic chain experiment, it was found that the LPO was reduced in Thamnocephalus platyurus (crustacean) fed with Pseudokirchneriella subcapitata (microalgae) exposed to 150 mg L À 1 carbamazepine for 24 h and in H. attenuata fed with the crustacean suggesting that redox activity of carbamazepine was at play (Vernouillet et al, 2010).…”

“…This helps to detect interferences of a contaminant with the environment before deeper alterations in the ecosystem occur (van der Oost et al, 2003). The Manila clam (Ruditapes philippinarum) have been applied as a model organism in several ecotoxicological studies because they are a sensitive species, easy to obtain and also maintain under laboratory conditions (Almeida et al, 2015;Matozzo et al, 2012;Martín-Díaz et al, 2004;Morales-Casselles et al, 2008a. Additionally, these species were selected for this study as their filtering feeding behavior provides them with the capacity to be in direct contact with pharmaceuticals which are dissolved in marine water.…”

Removal of Pharmaceuticals from Wastewater by Intermittent Electrocoagulation

“…At lower concentration (10 ng/L), DCF can impair osmoregulatory ability of a green shore crab Carcinus maenas [13]. Almeida et al [14] proved that beyond the threshold concentration of 3 µg/L, CBZ causes an impairment of antioxidant enzymes of the clam Ruditapes philippinarum. It can also affect the mortality, emergence and fertility of the non-biting midge Chironomus riparius at a concentration equal to 1.1 mg/kg [15].…”