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

Citation
Mo. James et al., 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, Drug metabolism and disposition, 25(3), 1997, pp. 346-354
Citations number
48
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00909556
Volume
25
Issue
3
Year of publication
1997
Pages
346 - 354
Database
ISI
SICI code
0090-9556(1997)25:3<346:DMOPAP>2.0.ZU;2-H
Abstract
These studies demonstrated that intestinal mucosa of the channel catfi sh contained activities comparable with liver for several phase 2 xeno biotic-metabolizing enzymes, and showed that CYP1A-dependent monooxyge nase activities were inducible in intestine but not liver by dietary e xposure to low concentrations of the Ah agonist, beta-naphthoflavone ( BNF), The diets administered were laboratory-prepared, semisynthetic p ellets of known composition, commercial chow, or chow supplemented wit h 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 semisynthe tic diet. Intestinal EROD and AHH activities were elevated by the comm ercial chow diet and further induced by supplementation with 10, but n ot 100, mg BNF/kg diet, In vitro studies showed that catfish EROD and AHH activities were sensitive to inhibition by BNF, with mean IC50 val ues of 0.078 and 2.2 mu M, respectively. Thus, residues of BNF retaine d in intestinal mucosa may have masked monooxygenase induction in catf ish 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 hep atic cytosol of catfish treated with BNF at the 10 mg/kg diet level re lative to chow controls, Epoxide hydrolase activity with styrene oxide as substrate was not affected by diet in intestinal microsomes.