Cross-sectional study of hepatic CYP1A and @entity5322 enzymes in hybrid @entity48243 , XXXX and @entity6373 following @entity5385 treatment.

@entity1 @entity12325 @entity4187 @entity5322 @entity5385 @entity4576 @entity48243 @entity6373
@entity5385 for Fish   ( @entity5385 , OTC) is one of three approved drugs for therapeutic treatment of fish in the United States. Nothing is known, however, of the effects of this therapeutic on drug metabolizing enzymes in fish post-treatment. The main purpose of the study was to examine whether the fish CYP1A and @entity5322 enzymes would cross-react with antibodies to known @entity1 @entity12325 forms ( @entity4187 and @entity5322 ). Observational feeding studies of OTC effects were conducted in hybrid @entity48243 , @entity4576 and @entity6373 . @entity5385 was mixed into the feed to achieve a daily dose of 82.8 mg per kg body weight at a feeding rate of 1% body weight per day. Hepatic microsomes of each fish were prepared and Western blotting of @entity4187 and CYP3A4 and enzyme assays of CYP1A2 and CYP3A4 were performed prior to OTC treatment and on post-treatment days 1, 6, 11 and 21. Both goat anti-rat @entity4187 and rabbit anti-human CYP3A4 showed good cross-reactivity with all three species in this study. All three species exhibited distinct perturbations in one or more of the variables examined on day 1 post-treatment. Immediately following the 10-day medication period, relative liver weight (RLW) of hybrid @entity48243 was increased 44% and remained elevated through post-treatment day 21. Increased CYP3A4 enzyme activity and protein abundance were noted in @entity4576 and @entity6373 , respectively. This observational approach demonstrated species differences both in control activities and in the timing and extent of hepatic responses to OTC. The unique perturbations of hepatic CYP450 enzymes in different fish species to OTC treatment observed in this study may have relevance for the use of additional antibiotics or other therapeutics used in aquaculture.
