Viral infection and PBDE exposure interact on CYP gene expression and enzyme activities in the mouse liver.

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.

[1]  R. Feigin,et al.  Textbook of Pediatric Infectious Diseases , 1986 .

[2]  T. Miyawaki,et al.  The relationship between serum levels of interleukin-6 and thyroid hormone in children with acute respiratory infection. , 1994, The Journal of clinical endocrinology and metabolism.

[3]  P. B. Larsen,et al.  Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. , 2001, Environmental health perspectives.

[4]  P. Darnerud,et al.  Common viral infection affects pentabrominated diphenyl ether (PBDE) distribution and metabolic and hormonal activities in mice. , 2005, Toxicology.

[5]  N. Bunce,et al.  Polybrominated diphenyl ethers as Ah receptor agonists and antagonists. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[6]  M. Cunningham,et al.  Differential expression of CYP1A, 2B, and 3A genes in the F344 rat following exposure to a polybrominated diphenyl ether mixture or individual components. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  K. Kannan,et al.  Occurrence of polybrominated biphenyls, polybrominated dibenzo-p-dioxins, and polybrominated dibenzofurans as impurities in commercial polybrominated diphenyl ether mixtures. , 2006, Environmental science & technology.

[8]  C. Tohyama,et al.  The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  G. M. Richardson,et al.  Is house dust the missing exposure pathway for PBDEs? An analysis of the urban fate and human exposure to PBDEs. , 2005, Environmental science & technology.

[10]  J. Fouts,et al.  A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. , 1980, Analytical biochemistry.

[11]  Ronald H Laessig,et al.  Polybrominated diphenyl ethers (PBDEs): new pollutants-old diseases. , 2003, Clinical medicine & research.

[12]  E. Morgan.  Regulation of cytochromes P450 during inflammation and infection. , 1997, Drug metabolism reviews.

[13]  P. Darnerud.  Toxic effects of brominated flame retardants in man and in wildlife. , 2003, Environment international.

[14]  L S Birnbaum,et al.  Toxicokinetics of BDE 47 in female mice: effect of dose, route of exposure, and time. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  Eva Jakobsson,et al.  Flame retardant exposure: polybrominated diphenyl ethers in blood from Swedish workers. , 1999 .

[16]  U. Siebert,et al.  Increased blood interleukin-10 mRNA levels in diseased free-ranging harbor porpoises (Phocoena phocoena). , 2007, Veterinary immunology and immunopathology.

[17]  S. Grande,et al.  Effects of Developmental Exposure to 2,2′,4,4′,5-Pentabromodiphenyl Ether (PBDE-99) on Sex Steroids, Sexual Development, and Sexually Dimorphic Behavior in Rats , 2005, Environmental health perspectives.

[18]  P. Darnerud,et al.  Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects. , 2002, Toxicology.

[19]  E. Hartree,et al.  Determination of protein: a modification of the Lowry method that gives a linear photometric response. , 1972, Analytical biochemistry.

[20]  Curtis D. Klaassen,et al.  Casarett and Doull's Toxicology. The Basic Science of Poisons , 1981 .

[21]  N. Bunce,et al.  Synthesis of polybrominated diphenyl ethers and their capacity to induce CYP1A by the Ah receptor mediated pathway. , 2001, Environmental science & technology.

[22]  A. K. Peters,et al.  Effects of polybrominated diphenyl ethers on basal and TCDD-induced ethoxyresorufin activity and cytochrome P450-1A1 expression in MCF-7, HepG2, and H4IIE cells. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  G. Friman,et al.  Effects of methyl mercury on cytokines, inflammation and virus clearance in a common infection (coxsackie B3 myocarditis). , 1996, Toxicology letters.

[24]  T. A. Richardson,et al.  Regulation of drug-metabolizing enzymes and transporters in inflammation. , 2006, Annual review of pharmacology and toxicology.

[25]  P. Kosch,et al.  Accelerated host metabolism of L-thyroxine during acute infection: role of the leukocyte and peripheral leukocytosis. , 1975, The Journal of clinical endocrinology and metabolism.

[26]  P. Darnerud,et al.  Induction of 7-ethoxyresorufin-O-deethylase (EROD) activity in mice foetuses by the PCB-congener 3,3',4,4'-tetrachlorobiphenyl. , 1993, Xenobiotica; the fate of foreign compounds in biological systems.

[27]  Heather M Stapleton,et al.  Polybrominated diphenyl ethers in house dust and clothes dryer lint. , 2005, Environmental science & technology.

[28]  G. Friman,et al.  Interactions Among Infections, Nutrients and Xenobiotics , 2007, Critical reviews in food science and nutrition.

[29]  P. Darnerud,et al.  Tissue localisation of tetra- and pentabromodiphenyl ether congeners (BDE-47, -85 and -99) in perinatal and adult C57BL mice. , 2006, Chemosphere.

[30]  N. Rose,et al.  Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity. , 2007, Methods.

[31]  I. Meerts,et al.  Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  J. Blomberg,et al.  A sensitive and quantitative single-tube real-time reverse transcriptase-PCR for detection of enteroviral RNA. , 2004, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[33]  Gloria D Jahnke,et al.  Thyroid toxicants: assessing reproductive health effects. , 2003, Environmental health perspectives.

[34]  A. K. Peters,et al.  Interactions of polybrominated diphenyl ethers with the aryl hydrocarbon receptor pathway. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[35]  P. Darnerud,et al.  Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice , 2001, Archives of Toxicology.

[36]  N. Kerkvliet,et al.  Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6J mice. , 1994, Toxicology.

[37]  A. El-Kadi,et al.  Cytochrome P450 down-regulation by serum from humans with a viral infection and from rabbits with an inflammatory reaction. , 2001, Drug metabolism and disposition: the biological fate of chemicals.