Chiral effects in the induction of drug-metabolizing enzymes using synthetic atropisomers of polychlorinated biphenyls (PCBs)

Michael Püttmann; Albrecht Mannschreck; Franz Oesch; Larry Robertson

doi:10.1016/0006-2952(89)90342-0

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Chiral effects in the induction of drug-metabolizing enzymes using synthetic atropisomers of polychlorinated biphenyls (PCBs)

Journal article

Peer reviewed

Chiral effects in the induction of drug-metabolizing enzymes using synthetic atropisomers of polychlorinated biphenyls (PCBs)

Michael Püttmann, Albrecht Mannschreck, Franz Oesch and Larry Robertson

Biochemical pharmacology, Vol.38(8), pp.1345-1352

1989

DOI: 10.1016/0006-2952(89)90342-0

PMID: 2495802

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Abstract

Atropisomers of the polychlorinated biphenyls 2,2',3,4,4',6-hexachlorobiphenyl (II) and 2,2',3,3',4,4',6,6'-octachlorobiphenyl (III), stable to racemization under physiological conditions, were administered to immature male Sprague-Dawley rats. The racemic hexachlorobiphenyl (II) was found to be a potent (phenobarbital-type) inducer, whereas (+)-II and (−)-II, administered at 100 μmol kg , showed clearly differing potencies as inducers with (+)-II enhancing aminopyrine N-demethylase, aldrin epoxidase and cytochrome P-450 content more potently than (−)-II. In contrast, the racemic octachlorobiphenyl (III) and its individual enantiomers were only weak phenobarbital-type inducers of cytochrome P-450, and the enantiomers of III were equally (weakly) potent. Separate studies conducted to investigate pharmacokinetic influences on the differential potency of the enantiomers of II showed that after 5 days the concentration of (+)-II in the liver was twice as high as that of its antipode. Therefore, enantioselectivity in disposition as well as in recognition may be responsible for the differential potency seen.

TCDD, 2,3,7,8-tetrachlorodibenzo- p-dioxin

EIC, ethyl isocyanide

and CO, carbon monoxide

MC, 3-methylcholanthrene

PB, phenobarbital

PBCs, polychlorinated biphenyls

TAC, triacetyl cellulose

Details

Title: Subtitle: Chiral effects in the induction of drug-metabolizing enzymes using synthetic atropisomers of polychlorinated biphenyls (PCBs)
Creators: Michael Püttmann - Johannes Gutenberg University Mainz
Albrecht Mannschreck - University of Regensburg
Franz Oesch - Johannes Gutenberg University Mainz
Larry Robertson - University of Kentucky
Resource Type: Journal article
Publication Details: Biochemical pharmacology, Vol.38(8), pp.1345-1352
Publisher: Elsevier Inc
DOI: 10.1016/0006-2952(89)90342-0
PMID: 2495802
ISSN: 0006-2952
eISSN: 1873-2968
Language: English
Date published: 1989
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984363603502771

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