Abstract
The effects of the 4-quinolones, oxolinic acid and flumequine on hepatic microsomal cytochrome P450 monooxygenases in rainbow trout were examined during this study. Following antibiotic administration in the diet for 10 days at a representative commercial medicated feed concentration, fish were killed for assay at various periods up to 12 days following 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 effects of flumequine were detectable 4 days earlier than those of oxolinic acid and lasted for less than ten days after treatment cessation. In contrast, oxolinic acid effects were apparent even on day 12 of the recovery period. The results of O-dealkylation, isoform-selective inhibition, and immunoblotting showed that the effects of both oxolinic acid and flumequine were related to P4501A subfamily. P450-binding spectra and experiments in vitro suggested that both antibiotics are weak dose-independent inhibitors of P450 activity, with flumequine exhibiting slightly higher binding affinity and inhibitory activity.
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