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Proposing urothelial and muscle in vitro cell models as a novel approach for assessment of long-term toxicity of nanoparticles
ID Skočaj, Matej (Author), ID Bizjak, Maruša (Author), ID Strojan, Klemen (Author), ID Lojk, Jasna (Author), ID Erdani-Kreft, Mateja (Author), ID Miš, Katarina (Author), ID Pirkmajer, Sergej (Author), ID Bregar, Vladimir Boštjan (Author), ID Veranič, Peter (Author), ID Pavlin, Mojca (Author)

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Abstract
Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the potential toxic effects of biomedical (polyacrylic acid and polyethylenimine coated magnetic NPs) and two industrial (SiO$_2$ and TiO$_2$) NPs following different short-term and long-term exposure protocols on two physiologically different in vitro models that are able to differentiate: L6 rat skeletal muscle cell line and biomimetic normal porcine urothelial (NPU) cells. We show that L6 cells are more sensitive to NP exposure then NPU cells. Transmission electron microscopy revealed an uptake of NPs into L6 cells but not NPU cells. In L6 cells, we obtained a dose-dependent reduction in cell viability and increased reactive oxygen species (ROS) formation after 24 h. Following continuous exposure, more stable TiO$_2$ and polyacrylic acid (PAA) NPs increased levels of nuclear factor Nrf2 mRNA, suggesting an oxidative damage-associated response. Furthermore, internalized magnetic PAA and TiO$_2$ NPs hindered the differentiation of L6 cells. We propose the use of L6 skeletal muscle cells and NPU cells as a novel approach for assessment of the potential long-term toxicity of relevant NPs that are found in the blood and/or can be secreted into the urine.

Language:English
Keywords:nanotoxicology, in vitro L6 rat skeletal muscle cell line, urothelium in vitro, differentiation, cell signaling, ROS
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:FE - Faculty of Electrical Engineering
MF - Faculty of Medicine
Publication status:Published
Publication version:Version of Record
Year:2020
Number of pages:23 str.
Numbering:Vol. 21, iss. 20, art. 7545
PID:20.500.12556/RUL-134469 This link opens in a new window
UDC:577
ISSN on article:1422-0067
DOI:10.3390/ijms21207545 This link opens in a new window
COBISS.SI-ID:32522243 This link opens in a new window
Publication date in RUL:17.01.2022
Views:848
Downloads:190
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
Publisher:MDPI
ISSN:1422-0067
COBISS.SI-ID:2779162 This link opens in a new window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:13.10.2020

Secondary language

Language:Slovenian
Keywords:nanotoksikologija, in vitro L6 mišična celična linija, urotelij, diferenciacija, celična signalizacija, ROS

Projects

Funder:ARRS - Slovenian Research Agency
Project number:J2-6758
Name:Razvoj in in vitro karakterizacija multimodalnih magnetnih nanodelcev za dostavo učinkovin in označevanje celic

Funder:ARRS - Slovenian Research Agency
Project number:J3-6794
Name:Celična energijska presnova kot tarča za zdravljenje raka – genski in farmakološki pristop

Funder:ARRS - Slovenian Research Agency
Project number:J7-7424
Name:Analiza možnih škodljivih učinkov nanodelcev in spremljajočih mehanizmov – od fizikalno-kemijske ter in vitro karakterizacije do aktivacije prirojenega imunskega sistema

Funder:ARRS - Slovenian Research Agency
Project number:J3-7494
Name:Tunelske membranske nanocevke za inovativno zdravljenje raka sečnega mehurja

Funder:ARRS - Slovenian Research Agency
Project number:P1-0055
Name:Biofizika polimerov, membran, gelov, koloidov in celic

Funder:ARRS - Slovenian Research Agency
Project number:P3-0108
Name:Diferenciacija urotelijskih celic

Funder:ARRS - Slovenian Research Agency
Project number:I0-0022
Name:Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)

Funder:ARRS - Slovenian Research Agency
Funding programme:Young researchers

Funder:ARRS - Slovenian Research Agency
Project number:P3-0043
Name:Molekularni mehanizmi razvoja in delovanja skeletne mišice

Funder:ARRS - Slovenian Research Agency
Project number:J7-7138
Name:Učinki novih metod v kardiokirurgiji

Funder:ARRS - Slovenian Research Agency
Project number:J7-8276
Name:Vpliv protirevmatičnih zdravil na inzulinsko rezistenco in energijsko presnovo v skeletni mišici

Funder:ARRS - Slovenian Research Agency
Project number:Z4-8229
Name:Vpliv različnih tipov nanodelcev na živčne celice in makrofage - analiza kratkoročnih in dolgoročnih posledic na celični stres, diferenciacijo in celično signaliziranje

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