Chiral effects in the induction of drug-metabolizing enzymes using synthetic atropisomers of polychlorinated biphenyls (PCBs). 1989

M Püttmann, and A Mannschreck, and F Oesch, and L Robertson
Institute of Toxicology, University of Mainz, FRG.

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 mumol/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.

UI MeSH Term Description Entries
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D011078 Polychlorinated Biphenyls Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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