HEPATIC P450 MONOOXYGENASE RESPONSE IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS (WALBAUM)) ADMINISTERED AQUACULTURE ANTIBIOTICS

The effects of the 4-quinolones, oxolinic acid and flumequine on hepat ic microsomal cytochrome P450 monooxygenases in rainbow trout were exa mined during this study. Following antibiotic administration in the di et for 10 days at a representative commercial medicated feed concentra tion, fish were killed for assay at various periods up to 12 days foll owing a return to normal diet. Ethoxyresorufin O-deethylase (EROD) and benzyloxyresorufin O-dealkylase (BROD) activities were significantly elevated as a result of antibiotic treatment. The effects of oxolinic acid were delayed and longer-lasting compared with flumequine. The eff ects of flumequine were detectable 4 days earlier than those of oxolin ic acid and lasted for less than ten days after treatment cessation. I n contrast, oxolinic acid effects were apparent even on day 12 of the recovery period. The results of O-dealkylation, isoform-selective inhi bition, and immunoblotting showed that the effects of both oxolinic ac id and flumequine were related to P4501A subfamily. P450-binding spect ra and experiments in vitro suggested that both antibiotics are weak d ose-independent inhibitors of P450 activity, with flumequine exhibitin g slightly higher binding affinity and inhibitory activity.