Proposing urothelial and muscle in vitro cell models as a novel approach for assessment of long-term toxicity of nanoparticles

Skočaj, Matej (author), Bizjak, Maruša (author), Strojan, Klemen (author), Lojk, Jasna (author), Erdani-Kreft, Mateja (author), Miš, Katarina (author), Pirkmajer, Sergej (author), Bregar, Vladimir Boštjan (author), Veranič, Peter (author), Pavlin, Mojca (author)

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
• UDC: 577
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms21207545
• COBISS.SI-ID: 32522243
• Publication date in RUL: 17.01.2022

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

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