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Viral infection and PBDE exposure interact on CYP gene expression and enzyme activities in the mouse liver
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (friman)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (friman)
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2007 (English)In: Toxicology, ISSN 0300-483X, Vol. 242, no 1-3, 100-108 p.Article in journal (Refereed) Published
Abstract [en]

In the present study coxsackievirus B3 (CVB3) adapted to Balb/c mice was used to examine whether infection affects xenobiotic-metabolising CYP1A1 and CYP2B gene expression (measured by RT-PCR) and the corresponding enzyme activities of ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-depentylase (PROD), as observed on day 3 of infection. To study the simultaneous effects of xenobiotic exposure, mice were administered the polybrominated diphenyl ether (PBDE) compounds BDE-99 (single congener) and Bromkal 70-5 DE (commercial mixture). Serum thyroxine levels were also measured. High numbers of CVB3 were found in the livers of infected mice but no significant effects of PBDE on virus replication were observed. In infected mice gene expression and CYP activities were decreased in comparison with non-infected mice, especially for CYP2B. PBDE exposure in the non-infected mice was characterised by an increase in both CYP2B and PROD levels/activities, whereas CYP1A levels increased and EROD activity decreased. In general, PBDE exposure in the infected mice did not increase EROD and PROD activities to the same extent as in the non-infected exposed mice. Infected mice exposed to BDE-99 showed significantly higher CYP2B and PROD levels than both the infected non-exposed and Bromkal-exposed groups. T(4) levels were greatly decreased by infection and a tendency of reduced T(4) levels after PBDE exposure could be observed in non-infected mice. In conclusion, infection reduced the detoxifying capacity of the liver and the serum T(4) levels. PBDE exposure can modify these effects. Notably, in the infected mice differences between BDE-99 and Bromkal were observed on CYP2B gene expression and PROD activity.

Place, publisher, year, edition, pages
2007. Vol. 242, no 1-3, 100-108 p.
Keyword [en]
Liver, Thyroxine, PBDE, CYP1A1, CYP2B, Coxsackievirus B3
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-102547DOI: 10.1016/j.tox.2007.09.014ISI: 000251699900012PubMedID: 17964055OAI: oai:DiVA.org:uu-102547DiVA: diva2:216335
Available from: 2009-05-07 Created: 2009-05-07 Last updated: 2010-03-11Bibliographically approved
In thesis
1. Coxsackievirus B3 Infection and Host Defence Responses Change the Metabolism of PBDE
Open this publication in new window or tab >>Coxsackievirus B3 Infection and Host Defence Responses Change the Metabolism of PBDE
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It has been suggested that the rising amounts of chemicals in the environment may affect host resistance and increase susceptibility to infections. Studies have also shown that infections can change the toxicity of pollutants. The aim of this thesis was to study interactions between environmental pollutant exposure in terms of polybrominated diphenyl ethers (PBDE) and a common human coxsackievirus B3 (CVB3) infection adapted to Balb/c mice. The studies focused on virus levels, cytokines, metabolising cytochrome P450 (CYP) enzymes and tissue distribution of PBDE.

A novel finding was an organ-specific effect of CVB3 infection on the metabolising capacity of PBDE. The PBDE metabolising enzyme CYP2B10 was down-regulated by the CVB3 infection in the liver, up-regulated in the lungs, but not affected in the pancreas. Accordingly, CVB3 infection increased the concentration of PBDE in the livers of infected mice. However, serum levels of PBDE were not affected by the infection, indicating that serum does not reflect the actual organ exposure of PBDE in infected individuals. The change in metabolising capacity was likely mediated by infection-induced cytokines and associated effects on the nuclear factor-κB (NF-κB) pathway.

PBDE drastically decreased serum levels of several cytokines and chemokines, an event that may create a slot for viruses to replicate. Accordingly, some results show that infected mice exposed to a high dose of PBDE had higher virus levels than mice exposed to a low dose.

In conclusion, infected individuals showed organ-specific changes in metabolism and tissue levels of PBDE, which potentially could change the toxicity of PBDE. PBDE also seems to affect the fate of the infection. NF-κB activated pathways may mediate one possible mechanism underlying these effects. Thus, further investigations of this pathway are warranted. In addition, future studies should address how PBDE exposure affects viral replication.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 73 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 487
Coxsackievirus, environmental pollutants, PBDE, cytokines, chemokines, metabolism, infection, tissue distribution, toxicology, virology, immunology
National Category
Pharmacology and Toxicology Microbiology in the medical area
Research subject
urn:nbn:se:uu:diva-108849 (URN)978-91-554-7619-9 (ISBN)
Public defence
2009-11-13, Universitetshuset, sal IV, Universitetsparken, Uppsala, 09:15 (Swedish)
Available from: 2009-10-27 Created: 2009-09-30 Last updated: 2009-10-27Bibliographically approved

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