PM15 Biomarkers
Exhibit Hall
8:00 AM - Monday
(PM249) Kinetics of phase I-II biotransformation kinetics in aquacultured finfish.
González, Jaime1, Reimschuessel, Renate2, Shaikh, Badar2, Kane, Andrew1, 1 University of Maryland College Park, College Park, Maryland, USA2 US Food and Drug Admiinstration, Center for Veterinary Medicine, Laurel, Maryland, USA
ABSTRACT- Currently there are only six drugs that are approved by the U.S. Food and Drug Administration for use in finfish aquaculture. Time consuming and costly processes have delayed the approval of additional, needed therapeutics. Kinetics of phase I-II biotransformation reactions were investigated in vitro to the feasibility of deriving species crop groupings, based in part of metabolic profiles. Model substrates for ethoxy- (EROD), pentoxy-(PROD), and benzyloxyresorufin (BROD)-o-dealkylations, UDP-glucuronosyltransferase (UDPGT), sulfotransferase (ST) and glutathione-s-transferase (GST) activities of several aquacultured fish species were studied to compare biotransformation profiles. Maximal velocity (Vmax), binding affinity (Km) and catalytic efficiency (Vmax/ Km) were used as endpoints for comparison among farm-raised rainbow trout (RBT), Atlantic salmon (AS), channel catfish (CC), striped bass (SB), hybrid striped bass (HSB), tilapia (TIL), bluegill (BG), and largemouth bass (LB). In general, kinetic parameters from species with relatively higher Vmax values also tended to have relatively higher binding affinities (i.e., lower Km values). RBT and AS had the highest Vmax/ Km ratios for EROD metabolism compared with the other species. PROD and BROD activity were not detected in any of the species. UDPGT Vmax/ Km ratios were highest in RBT, followed by AS, CC, TIL, LB, SB and HSB. ST Vmax/ Km ratios were highest in AS, SB, CC, followed by RBT, TIL, LB, HSB, followed by BG and TIL. GST Vmax/ Km ratios were highest in CC and TIL, followed by RBT and AS, followed by SB, LB, HSB and BG. Biotransformation profiles derived from this study show important differences in metabolic capabilities among fish species. These kinetic data are being used to develop a model for species crop groupings in support of new, safe therapeutics in U.S. aquaculture. This project was supported, in part, by the Joint Institute for Food Safety and Nutrition (JIFSAN).
Key words: biotransformation kinetics, fish, metabolism, aquaculture