PM15 Biomarkers
Exhibit Hall
8:00 AM - Monday
(PM250) Kinetics of hepatic albendazole sulfoxidation in channel catfish, tilapia and rainbow trout.
González, Jaime1, Reimschuessel, Renate2, Shaikh, Badar2, Gieseker, Charles2, Surfling, Stanley2, Kane, Andrew1, 1 University of Maryland College Park, College Park, Maryland, USA2 US Food and Drug Administration, Center for Veterinary Medicine, Laurel, Maryland, USA
ABSTRACT- Albendazole (ABZ) is a broad spectrum anthelmintic widely used in human and veterinary medicine, but is not currently approved for use in aquaculture. In order to better understand drug tissue residue dynamics in vitro biotransformation kinetics of ABZ was investigated using liver microsomes from market-size rainbow trout, channel catfish and tilapia. ABZ was transformed to a single metabolite, ABZ sulfoxide (ABZ-SO). Catfish had the highest (p<0.05) maximal velocity (Vmax = 264.0 ± 58.6 pmols ABZ-SO/min/mg protein) followed by tilapia (112.3 ± 8.2) and rainbow trout (73.3 ± 10.3). Binding affinity (Km, uM) varied significantly among the species: rainbow trout (3.9 ± 0.5), tilapia (9.2 ± 1.7) and catfish (22.0 ± 3.2). However, Vmax/Km ratios, a measure of enzyme efficiency, indicated no differences among the three species. In a second series of experiments, channel catfish were dosed in vivo with gel-food containing ABZ (10 mg/K PO). Fish were sacrificed at 24, 48, 72 and 120 hours after dosage. Control fish were fed ABZ-free feed. Induction of ethoxyresorufin-o-deethylase (EROD) activity was significant (p<0.05) in all ABZ-dosed treatments as compared to controls. EROD induction appeared higher in males and immature fish, than in females. No pentoxyresorufin- (PROD), benzyloxyresorufin-o-dealkylation (BROD) or glutathione-s-transferase (GST) induction was observed in the ABZ-treated fish. Additional competitive (co-incubation) assays with catfish and rainbow trout microsomes showed reduced EROD activity associated with the presence of ABZ in the incubation mixture. Conversely, the presence of 7-ethoxyresorufin did not alter the rate of ABZ sulfoxidation. in vitro hepatic metabolism of ABZ showed differences among fish species that need to be correlated with other studies to determine regulatory measures for therapeutic use and consumer safety guidelines. Data from these studies are being used to model drug tissue residues, and help develop species crop groupings in support of new, USFDA-approved therapeutics in U.S. aquaculture.
Key words: albendazole, fish, biotransformation, metabolism