Journal article
Subacute nicotine co-exposure has no effect on 2,2′,3,5′,6- pentachlorobiphenyl disposition but alters hepatic cytochrome P450 expression in the male rat
Toxicology (Amsterdam), Vol.338, pp.59-68
12/02/2015
DOI: 10.1016/j.tox.2015.10.002
PMCID: PMC4658283
PMID: 26463278
Abstract
Polychlorinated biphenyls (PCBs) are metabolized by cytochrome P450 2B enzymes (CYP2B) and nicotine is reported to alter CYP2B activity in the brain and liver. To test the hypothesis that nicotine influences PCB disposition, 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) and its metabolites were quantified in tissues of adult male Wistar rats exposed to PCB 95 (6mg/kg/d, p.o.) in the absence or presence of nicotine (1.0mg/kg/d of the tartrate salt, s.c.) for 7 consecutive days. PCB 95 was enantioselectively metabolized to hydroxylated (OH-) PCB metabolites, resulting in a pronounced enrichment of E1-PCB 95 in all tissues investigated. OH-PCBs were detected in blood and liver tissue, but were below the detection limit in adipose, brain and muscle tissues. Co-exposure to nicotine did not change PCB 95 disposition. CYP2B1 mRNA and CYP2B protein were not detected in brain tissues but were detected in liver. Co-exposure to nicotine and PCB 95 increased hepatic CYP2B1 mRNA but did not change CYP2B protein levels relative to vehicle control animals. However, hepatic CYP2B protein in animals co-exposed to PCB 95 and nicotine were reduced compared to animals that received only nicotine. Quantification of CYP2B3, CYP3A2 and CYP1A2 mRNA identified significant effects of nicotine and PCB 95 co-exposure on hepatic CYP3A2 and hippocampal CYP1A2 transcripts. Our findings suggest that nicotine co-exposure does not significantly influence PCB 95 disposition in the rat. However, these studies suggest a novel influence of PCB 95 and nicotine co-exposure on hepatic cytochrome P450 (P450) expression that may warrant further attention due to the increasing use of e-cigarettes and related products.
Details
- Title: Subtitle
- Subacute nicotine co-exposure has no effect on 2,2′,3,5′,6- pentachlorobiphenyl disposition but alters hepatic cytochrome P450 expression in the male rat
- Creators
- Marianna Stamou - Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USAEric Uwimana - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USABrenna M Flannery - Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USAIzabela Kania-Korwel - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USAHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USAPamela J Lein - Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA
- Resource Type
- Journal article
- Publication Details
- Toxicology (Amsterdam), Vol.338, pp.59-68
- DOI
- 10.1016/j.tox.2015.10.002
- PMID
- 26463278
- PMCID
- PMC4658283
- NLM abbreviation
- Toxicology
- ISSN
- 0300-483X
- eISSN
- 1879-3185
- Publisher
- Elsevier B.V
- Grant note
- name: National Institutes of Health National Institute of Environmental Health Sciences, award: R01 ES017425, P42 ES04699, P01 ES011269; DOI: 10.13039/100000139, name: United States Environmental Protection Agency, award: R833292
- Language
- English
- Date published
- 12/02/2015
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute
- Record Identifier
- 9984000929002771
Metrics
26 Record Views