title: The flame-retardant BDE-99 dose-dependently affects viral replication in CVB3-infected mice.
abstract: The flame retardant component 2,2',4,4',5-penta-BDE (BDE-99) is found in the environment and in human tissues and fluids. In mice the common human coxsackievirus B3 (CVB3) infection has been shown to change the tissue distribution of BDE-99. We now investigate how CVB3 infection in mice affects liver uptake of (14)C at two doses of radiolabelled BDE-99, and whether increased tissue levels are related to changed virus replication and gene expression of the proinflammatory chemokine monocyte chemoattractant protein-1 (MCP-1). Mice were infected on day 0, orally treated either with 200μg or 20mg (14)C-BDE-99/kgbw on day 1, and euthanised on day 3. Serum and liver levels of (14)C-BDE-99, as well as virus levels and gene expressions of MCP-1 in the liver, were measured. In non-infected mice, there was a dose-dependent uptake of BDE-99 in both liver and serum, and in infected animals the liver BDE-99 levels was further increased. When comparing infected mice exposed to the two BDE-99 doses, the higher BDE dose resulted in increased virus amounts in the liver, and decreased infection-induced expression of MCP-1. Consequently, a high enough dose/tissue concentration of BDE-99 may result in a disturbed mobilisation of immune cells into infected tissues that could explain higher virus titres and a possibly altered clinical course of the disease. Moreover, the fact that CVB3 infection increased the BDE-99 levels in liver but not in serum may impair the risk assessment of polybrominated diphenyl ethers (PBDEs) in subclinical and clinically infected individuals, as serum levels is the common marker of exposure.
authors: Risk Benefit Assessment Department, National Food Agency, Uppsala, Sweden.
authors: Magnus
authors: M
authors: Lundgren
authors: Per Ola
authors: PO
authors: Darnerud
authors: Nils-Gunnar
authors: NG
authors: Ilbäck
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D018932:Chemokine CCL2 / Q000235:genetics; D003384:Coxsackievirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000502:physiology; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011877:Radionuclide Imaging; D060888:Real-Time Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D002250:Carbon Radioisotopes; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers