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Atropselective Disposition of 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) and Identification of Its Metabolites in Mice with Liver-specific Deletion of Cytochrome P450 Reductase

preprint
submitted on 03.06.2019 and posted on 04.06.2019 by Xianai Wu, Guangshu Zhai, Jerald L. Schnoor, Hans-Joachim Lehmler
Cytochrome P450 enzymes oxidize chiral polychlorinated biphenyls (PCBs) to hydroxylated metabolites. Here we investigated the role of an impaired hepatic metabolism in the disposition of PCB 91 (CASRN 68194-05-8) in mice with a liver-specific deletion of the cpr gene (KO mice). KO mice and wild type (WT) mice were exposed to racemic PCB 91. Levels and enantiomeric fractions of PCB 91 and its metabolites were determined in tissues 3-days after PCB exposure. PCB 91 were higher in KO compared to WT mice. The liver of KO mice accumulated PCB 91 due to the high fat content in the liver of KO mice. 2,2',3,4',6-Pentachlorobiphenyl-5-ol was the major metabolite detected in all samples. PCB 91 and its metabolites displayed a genotype-dependent atropisomeric enrichment. These differences in atropselective disposition of PCB 91 and its metabolites are consistent with slower metabolism of PCB 91 in KO than WT mice and the accumulation of the parent PCB in the fatty liver of KO mice.

Funding

ES027169

ES013661

ES005605

History

Email Address of Submitting Author

hans-joachim-lehmler@uiowa.edu

Institution

University of Iowa

Country

USA

ORCID For Submitting Author

0000-0001-9163-927X

Declaration of Conflict of Interest

Nothing to declare

Exports