Modulation of erythromycin-induced biochemical responses in crucian carp by ketoconazole

The individual and combined biochemical responses of erythromycin and ketoconazole have been examined in an organism representative of the aquatic environment, crucian carp (Carassius auratus). The possible interactions between erythromycin and ketoconazole were investigated on the bioaccumulation and the expression of biotransformation enzymes 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST), and an antioxidant defense enzyme superoxide dismutase (SOD) in fish tissues. After 14 days of combined exposure (erythromycin + ketoconazole), the addition of ketoconazole at nominal concentrations of 0.2, 2, and 20 μg/L significantly increased the accumulation of erythromycin in fish bile; however, elevated erythromycin accumulation levels were not observed in the other test tissues. The inductions of EROD and SOD activity to erythromycin were inhibited by the combined exposure of ketoconazole in most cases; however, the GST activity returned to normal with exposure time and concentration of combined administration. From the tested pharmaceutical mixtures, it indicated that certain specific combinations may pose some perturbations in biochemical responses in fish and also provide a better understanding of the effects of toxic mixtures.