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Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity
Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O(2)(•)-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effe...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975067/ https://www.ncbi.nlm.nih.gov/pubmed/29351884 http://dx.doi.org/10.1016/j.redox.2018.01.006 |
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author | Grzelak, Agnieszka Wojewódzka, Maria Meczynska-Wielgosz, Sylwia Zuberek, Mariusz Wojciechowska, Dominika Kruszewski, Marcin |
author_facet | Grzelak, Agnieszka Wojewódzka, Maria Meczynska-Wielgosz, Sylwia Zuberek, Mariusz Wojciechowska, Dominika Kruszewski, Marcin |
author_sort | Grzelak, Agnieszka |
collection | PubMed |
description | Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O(2)(•)-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H(2)O(2) instead of O(2)(•)-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity. Altogether these results suggest that O(2)(•)- generated during NPs induced mitochondrial collapse is rapidly dismutated to H(2)O(2), which in the presence of iron ions undergoes a Fenton reaction to produce an extremely reactive hydroxyl radical ((•)OH). Clarification of the mechanism of NPs-dependent generation of (•)OH and demonstration of the crucial role of iron ions in NPs toxicity will facilitate our understanding of NPs toxicity and the design of safe nanomaterials. |
format | Online Article Text |
id | pubmed-5975067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59750672018-05-31 Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity Grzelak, Agnieszka Wojewódzka, Maria Meczynska-Wielgosz, Sylwia Zuberek, Mariusz Wojciechowska, Dominika Kruszewski, Marcin Redox Biol Research Paper Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O(2)(•)-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H(2)O(2) instead of O(2)(•)-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity. Altogether these results suggest that O(2)(•)- generated during NPs induced mitochondrial collapse is rapidly dismutated to H(2)O(2), which in the presence of iron ions undergoes a Fenton reaction to produce an extremely reactive hydroxyl radical ((•)OH). Clarification of the mechanism of NPs-dependent generation of (•)OH and demonstration of the crucial role of iron ions in NPs toxicity will facilitate our understanding of NPs toxicity and the design of safe nanomaterials. Elsevier 2018-01-09 /pmc/articles/PMC5975067/ /pubmed/29351884 http://dx.doi.org/10.1016/j.redox.2018.01.006 Text en © 2018 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Grzelak, Agnieszka Wojewódzka, Maria Meczynska-Wielgosz, Sylwia Zuberek, Mariusz Wojciechowska, Dominika Kruszewski, Marcin Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title | Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title_full | Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title_fullStr | Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title_full_unstemmed | Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title_short | Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity |
title_sort | crucial role of chelatable iron in silver nanoparticles induced dna damage and cytotoxicity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975067/ https://www.ncbi.nlm.nih.gov/pubmed/29351884 http://dx.doi.org/10.1016/j.redox.2018.01.006 |
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