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.
Lundgren
Magnus
M
Toxicology Division, National Food Administration, Uppsala, Sweden. magnus.lundgren@slv.se
Darnerud
Per Ola
PO
Molin
Ylva
Y
Lilienthal
Hellmuth
H
Blomberg
Jonas
J
Ilbäck
Nils-Gunnar
NG
D000818:Animals; D003384:Coxsackievirus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000187:drug effects / Q000472:pathogenicity; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010078:Oxazines / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
C477694:2,2',4,4',5-brominated diphenyl ether; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010078:Oxazines; D010647:Phenyl Ethers; C007649:ethoxyresorufin; C063747:Bromkal 70; C044943:pentoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D013974:Thyroxine