Journal article
Metabolism of 2,2 ',3,3 ',6,6 '-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent
Xenobiotica, Vol.43(11), pp.933-947
11/01/2013
DOI: 10.3109/00498254.2013.785626
PMCID: PMC3878182
PMID: 23581876
Abstract
1. Chiral polychlorinated biphenyls (PCBs) such as PCB 136 enantioselectively sensitize the ryanodine receptor (RyR). In light of recent evidence that PCBs cause developmental neurotoxicity via RyR-dependent mechanisms, this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs. However, enantioselective disposition of PCBs has not been fully characterized.
2. The effect of sex and cytochrome P450 (P450) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from naive control (CTL), phenobarbital (PB; CYP2B inducer) or dexamethasone (DEX; CYP3A inducer) pretreated adult Sprague-Dawley rats. PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups.
3. In liver tissue slices, hydroxylated PCB (OH-PCB) profiles depended on sex and inducer pretreatment, and OH-PCB levels followed the rank orders male > female and PB > DEX > CTL. In contrast, the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment. Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH-PCB metabolites were detected.
4. Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs.
Details
- Title: Subtitle
- Metabolism of 2,2 ',3,3 ',6,6 '-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent
- Creators
- Xianai Wu - University of IowaIzabela Kania-Korwel - University of IowaHao Chen - University of California, DavisMarianna Stamou - University of California, DavisKarigowda J. Dammanahalli - University of IowaMichael Duffel - University of IowaPamela J. Lein - University of California, DavisHans-Joachim Lehmler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Xenobiotica, Vol.43(11), pp.933-947
- DOI
- 10.3109/00498254.2013.785626
- PMID
- 23581876
- PMCID
- PMC3878182
- NLM abbreviation
- Xenobiotica
- ISSN
- 0049-8254
- eISSN
- 1366-5928
- Publisher
- Taylor & Francis
- Number of pages
- 15
- Grant note
- P42ES013661 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) ES05605; ES013661; ES017425; ES06694 / National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) ES04699 / UC Davis Superfund Basic Research Program
- Language
- English
- Date published
- 11/01/2013
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984285611602771
Metrics
13 Record Views