title: Intestinal bioavailability and biotransformation of 3,3',4,4'-tetrachlorobiphenyl (CB 77) in in situ preparations of channel catfish following dietary induction of CYP1A.
abstract: Previous studies with the catfish in situ perfused intestinal preparation have demonstrated a significant decline in the intestinal bioavailability of a coplanar polychlorinated biphenyl (PCB), 3,3',4,4'-tetrachlorobiphenyl (CB 77)(14C-TCB) dose in animals pre-exposed in vivo to TCB. This response was accompanied by CYP1A induction in the intestine, but little effect upon the oxidative metabolism of the subsequent in situ dose of [14C]-TCB. To ascertain the basis of these responses and the intestine specific contributions, the intestinal bioavailability and metabolism of [14C]-TCB were examined in the in situ intestinal preparation following in vivo exposure to beta-naphthoflavone (BNF; 0, 10 or 50 mg BNF/kg diet for 10 days), BNF was selected as a known inducer of CYP1A and as a compound with a structure unlikely to influence or directly partake in diffusion based TCB concentration gradients. Appreciable amounts of [14C]-TCB molar equivalents (Meq) reached the perfused circulation of the intestinal preparation for all treatments. While BNF pre-exposure elicited induction of CYP1A activities aryl hydrocarbon hydroxylase (AHH) (9.2-12.5-fold) and elicited modest morphological changes (muciparous) in the intestine these changes were not associated with alterations in [14C]-TCB Meq bioavailability. [14C]-TCB metabolism in the intestinal mucosa ranged between 0.54 and 1.27%, for all treatments. As with bioavailability, intestinal metabolism of [14C]-TCB was not significantly influenced in either extent or profile by induction of CYP1A activity as associated with BNF treatment. Four metabolites were found in mucosal sample extracts of which three were tentatively identified as 2-OH-TCB, 4-OH-3,3',4',5-TCB, and 4,4'-diOH-3,3',5,5' tetrachlorobiphenyl. A fourth unknown metabolite presented chromatographic characteristics suggestive of another dihydroxylated metabolite. These data when examined alone and compared to the literature suggest that the intestine may metabolize [14C]-TCB slowly and independent of CYP1A, resulting in somewhat different profiles than published for other organs. In addition, it is likely that previous [14C]-TCB bioavailability findings in the perfused intestine may be based on TCB concentration gradients rather than biotransformation.
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Doi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lou
authors.forename: Earnestine
authors.initials: E
authors.lastname: Holmes
authors.forename: Changaram S
authors.initials: CS
authors.lastname: Venugopal
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nyagode
authors.forename: Margaret O
authors.initials: MO
authors.lastname: James
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kleinow
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001682:Biological Availability; D001711:Biotransformation; D002247:Carbon Isotopes / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004032:Diet / Q000662:veterinary; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007059:Ictaluridae / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000633:toxicity; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D002247:Carbon Isotopes; D014874:Water Pollutants, Chemical; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl