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
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
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.