title: Inhibition of multixenobiotic resistance transporters (MXR) by silver nanoparticles and ions in vitro and in Daphnia magna.
abstract: The P-glycoprotein (P-gp, ABCB1) and multidrug resistance associated protein 1 (MRP1), important members of the ABC (ATP-binding cassette) transporters, protect cells and organisms via efflux of xenobiotics and are responsible for the phenomenon of multidrug or multixenobiotic resistance (MXR). In this study we first evaluated, in vitro, the interaction of silver nanoparticles (Ag NPs, 20, 23 and 27nm), Ag 200nm particles and Ag ions (AgNO3) with MXR efflux transporters using MDCKII and the P-gp over-expressing MDCKII-MDR1 cells and calcein-AM as a substrate of the transporters. Next the in vivo modulation of MXR activity was studied in Daphnia magna juveniles with the model P-gp and MRP1 inhibitors verapamil-HCl and MK571, respectively. The common environmental contaminants perfluorooctane sulfonate and bisphenol A, previously observed to interfere with the P-gp in vitro, also inhibited the efflux of calcein in vivo. Small-sized Ag NPs (with biomolecules present on the surface) and AgNO3 inhibited the MXR activity in daphnids and MDCKII-MDR1 cells, but abcb1 gene expression remained unchanged. Both Ag NPs and dissolved ions contributed to the effects. This study provides evidence of the interference of Ag NPs and AgNO3 with the MXR activity both in vitro and in D. magna, and should be taken into account when Ag NP toxicity is assessed.
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Georgantzopoulou
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cambier
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Serchi
authors.affiliation: Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland; Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Dorodna 16, 03-195 Warszawa, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore, Tamilnadu, India.
authors.forename: Yekkuni L
authors.initials: YL
authors.lastname: Balachandran
authors.affiliation: Materials Research and Technology Department (MRT), Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Patrick
authors.initials: P
authors.lastname: Grysan
authors.affiliation: Materials Research and Technology Department (MRT), Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Audinot
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ziebel
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Cédric
authors.initials: C
authors.lastname: Guignard
authors.affiliation: Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5 avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg. Electronic address: arno.gutleb@list.lu.
authors.forename: Arno C
authors.initials: AC
authors.lastname: Gutleb
authors.affiliation: Marine Animal Ecology Group, Wageningen University, Wageningen, The Netherlands; Wageningen Institute for Marine Resources & Ecosystem Studies, IMARES, IJmuiden, The Netherlands. Electronic address: tinka.murk@wur.nl.
authors.forename: AlberTinka J
authors.initials: AJ
authors.lastname: Murk
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000818:Animals; D060829:Arthropod Proteins / Q000378:metabolism; D003621:Daphnia / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004785:Environmental Pollutants / Q000633:toxicity*; D061985:Madin Darby Canine Kidney Cells; D053768:Metal Nanoparticles / Q000633:toxicity*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D012834:Silver / Q000633:toxicity*; D012835:Silver Nitrate / Q000633:toxicity*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D060829:Arthropod Proteins; D004785:Environmental Pollutants; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012834:Silver; D012835:Silver Nitrate; C513055:ABCB1 protein, human
keywords: Cellular efflux transporters; Daphnia magna; MDCKII-MDR1; MDR/MXR; P-glycoprotein; Silver nanoparticles