Interactive effects of selected pharmaceutical mixtures on bioaccumulation and biochemical status in crucian carp (Carassius auratus)

• Crucian carp was exposed to three pharmaceuticals alone and in binary combination.
• Addition of FLU increased ROX and PRP accumulation in liver of crucian carp.
• FLU inhibited metabolism response to ROX and PRP at catalytic and mRNA levels.
• ROX + FLU and PRP + FLU treatments induced higher oxidative stress than sole chemical.

The aim of this study was to evaluate the interactive effects of fluoxetine (FLU), roxithromycin (ROX) and propranolol (PRP) on the bioaccumulation and biochemical responses in the crucian carp Carassius auratus. After 7 days of binary exposure (ROX + FLU and PRP + FLU), the addition of waterborne FLU at nominal concentrations of 4, 20 and 100 μg L−1 significantly increased the accumulation of ROX and PRP in fish livers in most cases, although elevated ROX and PRP bioaccumulation levels were not observed in muscles or gills. The inductive response of 7-ethoxyresorufin O-deethylase (EROD) to PRP and that of 7-benzyloxy-4-trifluoromethyl-coumarin O-dibenzyloxylase (BFCOD) to ROX were inhibited by the co-administration of FLU at all tested concentrations. Correspondingly, marked inhibition of CYP1A and CYP3A mRNA expression levels was observed in the livers of fish co-treated with FLU + PRP and FLU + ROX relative to their PRP- and ROX-only counterparts, respectively. In addition, as reflected by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, co-exposure to ROX + FLU and PRP + FLU seemed to induce stronger antioxidant responses than single pharmaceutical exposure in fish livers. This work indicated that the interactive effects of pharmaceutical mixtures could lead to perturbations in the bioaccumulation and biochemical responses in fish.