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Effects of antimicrobial drugs upon P450 enzymes in fish

Numerous pharmaceuticals are metabolized by P450 enzymes in fish, which makes them of critical importance both for detoxification and formation of toxic metabolites. Therefore, a better understanding of the role of each cytochrome P450 in drug metabolism and drug-induced toxicity is vital. At this time, however, most research on the P450 system in fish has been done on environmental factors that influence P450 induction. Much less is known about metabolism of aquaculture antibiotics by the cytochrome P450 system. Despite strict regulations, except via medicated feed, fish may get exposed to antimicrobial drugs via aquatic environment. Discharge from sewage treatment plants has been identified as their primary source. The differences in responses of CYP enzymes in different fish species to antimicrobial treatment may have relevance for the use of antimicrobials in aquaculture. The variable effects in the response among different fish species to antimicrobial drugs is a valid reason to critically use assays developed for mammals for evaluating drug response in various fishes. Also, the use of antibodies to CYP enzymes across phyla can be of value if caution is exercised in the interpretation. Substrates developed for use in mammalian systems have been assayed in fish, and are useful for CYP-mediated functional comparison between mammalian and fish species. Standardized protocols for drug impact on fish P450 will facilitate those studies and standards will be necessary for the future application on fishes.

cytochrome P450 enzymes; fish; biotransformation; antimicrobial therapy

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