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Acute Effects of Vi...
Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier
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Bloise, E (författare)
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- Petropoulos, S (författare)
- Karolinska Institutet
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Iqbal, M (författare)
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Kostaki, A (författare)
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Ortiga-Carvalho, TM (författare)
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Gibb, W (författare)
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Matthews, SG (författare)
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(creator_code:org_t)
- 2017-02-22
- 2017
- Engelska.
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Ingår i: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. - : S. Karger AG. - 1421-9778. ; 41:3, s. 1044-1050
- Relaterad länk:
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https://www.karger.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB). As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C), increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5) were injected (i.p.) with PolyI:C (5 mg/kg or 10 mg/kg) or vehicle (saline). [3H]digoxin (P-gp substrate) was injected (i.v.) 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus), and fetal brains were collected. Results: PolyI:C exposure (4h) significantly elevated maternal plasma IL-6 (P<0.001) and increased [3H]digoxin accumulation in the fetal brain (P<0.05). In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.
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