Gadolinium (Gd)-based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier-based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd-complexes (Gd-lip) co-encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathological states including stroke. In this study, we evaluated nanosafety of Gd-lip containing PE-DTPA chelating Gd+3 prepared by lipid film hydration method. We detected no cytotoxicity of Gd-lip in human liver cells including cancer HepG2, progenitor (non-differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd-lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metabolism in differentiated HepaRG. Moreover, Gd-lip did not show pro-inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd-lip with respect to hepatotoxicity and immunopathology caused by inflammation.

• MeSH
• diethylentriaminpentaacetát gadolinia * škodlivé účinky   toxicita   MeSH
• fibrinolytika MeSH
• fosfatidylethanolaminy * škodlivé účinky   toxicita   MeSH
• hepatocyty účinky léků   MeSH
• inflamasomy MeSH
• kontrastní látky * MeSH
• kultivované buňky MeSH
• lidé MeSH
• liposomy * MeSH
• magnetická rezonanční tomografie * MeSH
• makrofágy účinky léků   MeSH
• nanočástice MeSH
• nosiče léků * MeSH
• protein NLRP3 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diethylentriaminpentaacetát gadolinia * MeSH
• fibrinolytika MeSH
• fosfatidylethanolaminy * MeSH
• gadolinium phosphatidylethanolamine-DTPA MeSH Prohlížeč
• inflamasomy MeSH
• kontrastní látky * MeSH
• liposomy * MeSH
• NLRP3 protein, human MeSH Prohlížeč
• nosiče léků * MeSH
• protein NLRP3 MeSH

Effects of airborne particles on the expression status of markers of cellular toxic stress and on the release of eicosanoids, linked with inflammation and oxidative damage, remain poorly characterized. Therefore, we proposed a set of various methodological approaches in order to address complexity of PM0.5-induced toxicity. For this purpose, we used a well-characterized model of A549 pulmonary epithelial cells exposed to a non-cytotoxic concentration of ambient aerosol particle fraction PM0.5 for 24 h. Electron microscopy confirmed accumulation of PM0.5 within A549 cells, yet, autophagy was not induced. Expression profiles of various cellular stress response genes that have been previously shown to be involved in early stress responses, namely unfolded protein response, DNA damage response, and in aryl hydrocarbon receptor (AhR) and p53 signaling, were analyzed. This analysis revealed induction of GREM1, EGR1, CYP1A1, CDK1A, PUMA, NOXA and GDF15 and suppression of SOX9 in response to PM0.5 exposure. Analysis of eicosanoids showed no oxidative damage and only a weak anti-inflammatory response. In conclusion, this study helps to identify novel gene markers, GREM1, EGR1, GDF15 and SOX9, that may represent a valuable tool for routine testing of PM0.5-induced in vitro toxicity in lung epithelial cells.

• Klíčová slova
• AhR, PM0.5, early stress response, eicosanoids, inflammation, p53, ultrafine particulate matter, unfolded protein response (UPR),
• MeSH
• aerosoly MeSH
• buňky A549 MeSH
• epitelové buňky metabolismus   patologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• pevné částice toxicita   MeSH
• plíce metabolismus   patologie   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aerosoly MeSH
• látky znečišťující vzduch MeSH
• pevné částice MeSH