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0090-9556/97/2503-0346-0354$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 3

Dietary Modulation of Phase 1 and Phase 2 Activities with Benzo(a)pyrene and Related Compounds in the Intestine But Not the Liver of the Channel Catfish, Ictalurus punctatus

Margaret O. James, Allen H. Altman, Karen Morris, Kevin M. Kleinow, and Zeen Tong

Department of Medicinal Chemistry (M.O.J., Z.T.), University of Florida-Gainesville; The Whitney Laboratory (M.O.J., A.H.A., K.M.), University of Florida-St. Augustine; and Department of Veterinary Physiology, Pharmacology, and Toxicology (K.M.K.), Louisiana State University

These studies demonstrated that intestinal mucosa of the channel catfish contained activities comparable with liver for several phase 2 xenobiotic-metabolizing enzymes, and showed that CYP1A-dependent monooxygenase activities were inducible in intestine but not liver by dietary exposure to low concentrations of the Ah agonist, beta -naphthoflavone (BNF). The diets administered were laboratory-prepared, semisynthetic pellets of known composition, commercial chow, or chow supplemented with BNF at 10 or 100 mg BNF/kg chow. Very low intestinal benzo(a)pyrene hydroxylase [aryl hydrocarbon hydroxylase (AHH)] and ethoxyresorufin O-deethylase (EROD) activities were found in catfish fed the semisynthetic diet. Intestinal EROD and AHH activities were elevated by the commercial chow diet and further induced by supplementation with 10, but not 100, mg BNF/kg diet. In vitro studies showed that catfish EROD and AHH activities were sensitive to inhibition by BNF, with mean IC50 values of 0.078 and 2.2 µM, respectively. Thus, residues of BNF retained in intestinal mucosa may have masked monooxygenase induction in catfish fed the 100 mg BNF/kg diet. Microsomal UDP-glucuronosyltransferase and cytosolic PAPS-sulfotransferase activities with 3-hydroxybenzo(a)pyrene as substrate were largely unaffected by the diets studied, and intestinal activities were similar to hepatic activities. Glutathione S-transferase activity was slightly induced in intestinal, but not hepatic cytosol of catfish treated with BNF at the 10 mg/kg diet level relative to chow controls. Epoxide hydrolase activity with styrene oxide as substrate was not affected by diet in intestinal microsomes.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.