Absence of Active Drug Metabolizing Enzymes In The Livers Of Hatchery-Raised Redfish
IAAAM Archive
Larry P. Flood1; Michael Alderman1; Michael J. Carvan, III1; Delbert Gatlin2; David Bus bee1
1Department of Veterinary Anatomy and Public Health, Texas Veterinary Medical Center; 2Department of Wildlife and Fisheries, Texas A & M University, College Station, TX

The cytochrome P450 (P450) enzyme system is the predominant oxidative enzyme system involved in phase I biotransformation of xeno- and endobiotics. These enzymes function to increase the hydrophilicity of molecules to aid in excretion and/or precede further biotransformation via phase II enzymes. Many xeno and endobiotic chemicals, including drugs, steroid hormones, fatty acids, bile acids and hydrocarbon pollutants are substrates of P450s and are capable of inducing the expression of P450 enzymes. In general, increased P450 activity is the result of an increase in the rate of enzyme synthesis, and is followed by a corresponding rise in biotransformation of the inducing chemical.

Specific cytochrome P450 enzyme parameters were investigated in redfish, a popular U.S. gulf coast aquaculture and game fish species. Microsomal P450 concentration, 7-ethoxyresorufin-O-deethylase (EROD) and NADPH cytochrome P450 reductase catalytic activities were compared in hatchery-raised (induced and un-induced) and wild-caught specimens. Our data indicate a complete absence of active P450 in hatchery-raised redfish; however, spectral and SDS-PAGE analyses indicate the presence of P420, the denatured form of P450, in these animals. EROD catalytic activity was not present in hatchery-raised redfish whereas wild caught fish exhibited detectable P450 and significant EROD activity. NADPH cytochrome P450 reductase, an integral component in P450 biotransformation, was present in hatchery-raised fish, suggesting that the lack of EROD catalytic activity was due to the absence of active P450 enzyme. EROD catalytic activity in hatchery-raised fish exhibited no sexual maturity- or diet-related alterations. Upon gross examination of the tissues from hatchery-raised fish, the livers appeared fatty and discolored and were often bile-stained. Tissues from wild-caught fish appeared to be normal. Histopathologic examination of hepatic tissues was inconclusive.

Hatchery-raised redfish appeared to have abnormal livers which may be associated with the absence of active P450 enzymes. These data suggest that hatchery-raised fish have a severely reduced/absent drug metabolizing capability with potentially dangerous therapeutic and/or toxicological implications.

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Larry P. Flood


MAIN : Therapeutics : Drug Metabolizing Enzymes
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