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dc.contributor.author
Blazquez, Alba G.
dc.contributor.author
Briz, Oscar
dc.contributor.author
Gonzalez Sanchez, Ester
dc.contributor.author
Perez, Maria J.
dc.contributor.author
Ghanem, Carolina Inés
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dc.contributor.author
Marin, Jose J. G.
dc.date.available
2017-03-30T15:44:11Z
dc.date.issued
2014-05
dc.identifier.citation
Blazquez, Alba G.; Briz, Oscar; Gonzalez Sanchez, Ester; Perez, Maria J.; Ghanem, Carolina Inés; et al.; The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis; Elsevier Inc; Toxicology And Applied Pharmacology; 277; 1; 5-2014; 77-84
dc.identifier.issn
0041-008X
dc.identifier.uri
http://hdl.handle.net/11336/14509
dc.description.abstract
Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Inc
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Bcrp
dc.subject
Maternal Cholestasis
dc.subject
Acetaminophen
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Abc Transporters
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Drug Liver
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Paracetamol
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Pregnancy
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Transport
dc.subject.classification
Otras Ciencias de la Salud
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dc.subject.classification
Ciencias de la Salud
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-06T17:07:03Z
dc.journal.volume
277
dc.journal.number
1
dc.journal.pagination
77-84
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Blazquez, Alba G.. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España
dc.description.fil
Fil: Briz, Oscar. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España
dc.description.fil
Fil: Gonzalez Sanchez, Ester. Universidad de Salamanca; España
dc.description.fil
Fil: Perez, Maria J.. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España
dc.description.fil
Fil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Marin, Jose J. G.. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España
dc.journal.title
Toxicology And Applied Pharmacology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0041008X14000817
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.taap.2014.02.019
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