Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its effects in biochemical responses.

1. Laboratory experiments were carried out to assess uptake and metabolism of the epilepsy drug, carbamazepine and its consequent biological responses in marine clam (Ruditapes decussatus) a model non-target organism in ecotoxicology. 2. Clams were exposed to two nominal concentrations (C1 = 30 μg/L and C2 = 50 μg/L) of CBZ for a maximum period of 14 days. Analysis of CBZ and their metabolites in clam and water after exposure to two nominal concentrations of the pharmaceutical drug were performed using UPLC-HRMS analysis. CBZ accumulation reached an average tissue concentration of 1241.59 ng/g dw and 1664.33 ng/g dw at low and high nominal concentration, respectively. 3. Furthermore, a metabolite (3-hydroxy-CBZ) was detected in tissues indicating carbamazepine translocation and metabolism inside clam, suspect screening of CBZ glucuronides was also performed by accurate mass extraction but it could not be detected. 4.  Activities of antioxidant enzymes superoxide dismutase, catalase and gluthatione-S-transferase generally increased. Change in the contents of glutathione, malondialdehyde and protein carbonyl were also studied. 5.  Results indicated that the bioaccumulation of CBZ resulted in the changes of the antioxidant defense system and the production of ROS with the oxidative stress, ultimately induced alteration in lipid peroxidation and protein carbonyl.