Hepatic metabolism affects the atropselective disposition of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice.
作者： Xianai Wu , Christopher Barnhart , Pamela J. Lein , Hans-Joachim Lehmler
DOI: 10.1021/ES504766P
关键词: Metabolite 、 Chemistry 、 Wild type 、 Enzyme 、 Drug metabolism 、 Cytochrome P450 、 Enantiomer 、 Endocrinology 、 Internal medicine 、 Excretion 、 Hydroxylation
摘要: To understand the role of hepatic vs extrahepatic metabolism in disposition chiral PCBs, we studied 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) and its hydroxylated metabolites (HO-PCBs) mice with defective due to liver-specific deletion cytochrome P450 oxidoreductase (KO mice). Female KO congenic wild type (WT) were treated racemic PCB 136, levels signatures 136 HO-PCBs determined tissues excreta 3 days after administration. tissue higher compared WT mice. Feces was a major route metabolite excretion, 2,2',3,3',6,6'-hexachlorobiphenyl-5-ol being recovered from feces. (+)-PCB second eluting atropisomers, enriched all excreta. The atropisomers blood liver; an exception displayed enrichment first atropisomers. Fecal HO-PCB changed time differed between mice, larger enantiomeric fractions Our results demonstrate that and, possibly, (P450) enzymes play PCBs.
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