Effect of 7,8-benzoflavone pretreatment on diethylstilbestrol metabolism, drug-metabolising enzymes and the aromatic hydrocarbon (Ah) receptor in male hamster liver.
Pretreatment of male Syrian golden hamsters with 7,8-benzoflavone (7,8-BF) leads to a marked increase of cytochrome P450 and cytochrome b5 levels in the liver, whereas phenobarbital (PB) and 3-methylcholanthrene (MC) induce cytochrome P450 but not cytochrome b5 7,8-BF pretreatment has only minor effects on the activities of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin-O-deethylase, but 7-ethoxyresorufin-O-deethylase is increased 3-fold. In contrast to PB, pretreatment with 7,8-BF or MC reduces the oxidative metabolism of diethylstilbestrol (DES) by hepatic microsomes in vitro. The cytosolic level of the aromatic hydrocarbon (Ah) receptor in hamster liver is decreased by 7,8-BF and slightly enhanced by MC pretreatment. PB increases the receptor level 1.5-fold. The affinity of 7,8-BF to the Ah receptor in vitro is of the same order of magnitude as that of the known ligands 5,6-benzoflavone and 2,3,7,8-tetrachlorodibenzofurane. PB and DES show no binding to the receptor protein.
Blaich
G
G
Institute of Pharmacology and Toxicology, University of Würzburg, FRG.
Göttlicher
M
M
Cikryt
P
P
Metzler
M
M
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D006838:Hydrocarbons / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D010599:Pharmacokinetics / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000032:analysis / Q000502:physiology*
D001571:Benzoflavones; D005419:Flavonoids; D006838:Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D004054:Diethylstilbestrol; D010634:Phenobarbital