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Basic Clin Pharmacol Toxicol ; 126(4): 374-388, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31628893

RESUMO

Asbestos (Mg-hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter-length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg- and two NiNTs of different lengths were assessed for cytotoxicity and pro-inflammatory responses in THP-1 macrophages and human bronchial epithelial lung cells (HBEC3-KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET- and BJH analysis, and chemical composition by XRD. The different Mg- and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro-inflammatory cytokines in THP-1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3-KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF-ß responses than chrysotile in both cell models. In conclusion, the pro-inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP-1 macrophages, but not in HBEC3-KT cells. Notably, the shortest NTs showed no or little pro-inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.


Assuntos
Asbestos Serpentinas/toxicidade , Inflamação/induzido quimicamente , Pulmão/patologia , Nanotubos , Asbestos Serpentinas/administração & dosagem , Asbestos Serpentinas/química , Brônquios/citologia , Brônquios/patologia , Linhagem Celular , Células Cultivadas , Citocinas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/patologia , Humanos , Inflamação/patologia , Pulmão/citologia , Macrófagos/patologia , Nanopartículas , Dióxido de Silício/administração & dosagem , Dióxido de Silício/toxicidade
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