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Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue
In light of recent developments in nanotechnologies, interest is growing to better comprehend the interaction of nanoparticles with body tissues, in particular within the cardiovascular system. Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Na...
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| Published in: | Particle and fibre toxicology 2014-12, Vol.11 (1), p.63, Article 63 |
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| creator | Savi, Monia Rossi, Stefano Bocchi, Leonardo Gennaccaro, Laura Cacciani, Francesca Perotti, Alessio Amidani, Davide Alinovi, Rossella Goldoni, Matteo Aliatis, Irene Lottici, Pier Paolo Bersani, Danilo Campanini, Marco Pinelli, Silvana Petyx, Marta Frati, Caterina Gervasi, Andrea Urbanek, Konrad Quaini, Federico Buschini, Annamaria Stilli, Donatella Rivetti, Claudio Macchi, Emilio Mutti, Antonio Miragoli, Michele Zaniboni, Massimiliano |
| description | In light of recent developments in nanotechnologies, interest is growing to better comprehend the interaction of nanoparticles with body tissues, in particular within the cardiovascular system. Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Nanoparticles |
| doi_str_mv | 10.1186/s12989-014-0063-3 |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4349471</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A539684083</galeid><sourcerecordid>A539684083</sourcerecordid><originalsourceid>FETCH-LOGICAL-c500t-9308b1ac4c272ca2f6eb1fd5223a4a21a6009f09851f319e51a0ff6ff9a935e33</originalsourceid><addsrcrecordid>eNptkctqHDEQRYWJ8Sv5gGyCICsv2pZa6oc2AWMc22AI2M5a1KhLMxWmpUHS-PH36WFi44FQCxXSubdUXMa-SnEmZd-eZ1mb3lRC6kqIVlVqjx3JTquqN1336UN_yI5z_iOEavpGHrDDutF9p6Q-Yu6RCgRaj3yg-EID8gAhriAVckvMfJXiGAtySGnxWhYjQeZPBBwmPqErnELBBK5QDPyZyoInKNxBGggcL5TzGj-zfQ_LjF_-nSfs98-rx8ub6u7X9e3lxV3lGiFKZZToZxKcdnVXO6h9izPph6auFWioJbRCGC_MtIJX0mAjQXjfem_AqAaVOmE_tr6r9WzEwWEoCZZ2lWiE9GojkN19CbSw8_hktdJGd3Iy-L41mMMSLQUfJ8yNlJ29aJRpey36zZiz_1BTDTiSiwE9Tfc7gtMdwcQUfClzWOdsbx_ud1m5ZV2KOSf079-Xwm5Ct9vQ7RS63YRuN5pvH_d-V7ylrP4CFG6o_A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue</title><source>Full-Text Journals in Chemistry (Open access)</source><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Savi, Monia ; Rossi, Stefano ; Bocchi, Leonardo ; Gennaccaro, Laura ; Cacciani, Francesca ; Perotti, Alessio ; Amidani, Davide ; Alinovi, Rossella ; Goldoni, Matteo ; Aliatis, Irene ; Lottici, Pier Paolo ; Bersani, Danilo ; Campanini, Marco ; Pinelli, Silvana ; Petyx, Marta ; Frati, Caterina ; Gervasi, Andrea ; Urbanek, Konrad ; Quaini, Federico ; Buschini, Annamaria ; Stilli, Donatella ; Rivetti, Claudio ; Macchi, Emilio ; Mutti, Antonio ; Miragoli, Michele ; Zaniboni, Massimiliano</creator><creatorcontrib>Savi, Monia ; Rossi, Stefano ; Bocchi, Leonardo ; Gennaccaro, Laura ; Cacciani, Francesca ; Perotti, Alessio ; Amidani, Davide ; Alinovi, Rossella ; Goldoni, Matteo ; Aliatis, Irene ; Lottici, Pier Paolo ; Bersani, Danilo ; Campanini, Marco ; Pinelli, Silvana ; Petyx, Marta ; Frati, Caterina ; Gervasi, Andrea ; Urbanek, Konrad ; Quaini, Federico ; Buschini, Annamaria ; Stilli, Donatella ; Rivetti, Claudio ; Macchi, Emilio ; Mutti, Antonio ; Miragoli, Michele ; Zaniboni, Massimiliano</creatorcontrib><description>In light of recent developments in nanotechnologies, interest is growing to better comprehend the interaction of nanoparticles with body tissues, in particular within the cardiovascular system. Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Nanoparticles <50 nm in size are known to pass the alveolar-pulmonary barrier, enter into bloodstream and induce inflammation, but the direct pathogenic mechanisms still need to be evaluated. We thus focused our attention on titanium dioxide (TiO₂) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body.
We conducted functional studies on isolated adult rat cardiomyocytes exposed acutely in vitro to TiO₂ and on healthy rats administered a single dose of 2 mg/Kg TiO₂ NPs via the trachea. Transmission electron microscopy was used to verify the actual presence of TiO₂ nanoparticles within cardiac tissue, toxicological assays were used to assess lipid peroxidation and DNA tissue damage, and an in silico method was used to model the effect on action potential.
Ventricular myocytes exposed in vitro to TiO₂ had significantly reduced action potential duration, impairment of sarcomere shortening and decreased stability of resting membrane potential. In vivo, a single intra-tracheal administration of saline solution containing TiO₂ nanoparticles increased cardiac conduction velocity and tissue excitability, resulting in an enhanced propensity for inducible arrhythmias. Computational modeling of ventricular action potential indicated that a membrane leakage could account for the nanoparticle-induced effects measured on real cardiomyocytes.
Acute exposure to TiO₂ nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.</description><identifier>ISSN: 1743-8977</identifier><identifier>EISSN: 1743-8977</identifier><identifier>DOI: 10.1186/s12989-014-0063-3</identifier><identifier>PMID: 25487314</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Action Potentials - drug effects ; Air Pollutants - toxicity ; Animals ; Arrhythmias, Cardiac - chemically induced ; Arrhythmias, Cardiac - physiopathology ; Cell Membrane Permeability - drug effects ; Cells, Cultured ; Computer Simulation ; DNA Damage ; Excitation Contraction Coupling - drug effects ; Health aspects ; Heart ; Heart Conduction System - drug effects ; Heart Conduction System - physiopathology ; Heart Ventricles - cytology ; Heart Ventricles - drug effects ; Heart Ventricles - physiopathology ; Heart Ventricles - ultrastructure ; Inhalation Exposure - adverse effects ; Lipid Peroxidation - drug effects ; Male ; Metal Nanoparticles - administration & dosage ; Metal Nanoparticles - toxicity ; Models, Biological ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - ultrastructure ; Pollution ; Rats, Wistar ; Titanium - administration & dosage ; Titanium - toxicity ; Toxicity Tests, Acute</subject><ispartof>Particle and fibre toxicology, 2014-12, Vol.11 (1), p.63, Article 63</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>Savi et al.; licensee BioMed Central. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-9308b1ac4c272ca2f6eb1fd5223a4a21a6009f09851f319e51a0ff6ff9a935e33</citedby><cites>FETCH-LOGICAL-c500t-9308b1ac4c272ca2f6eb1fd5223a4a21a6009f09851f319e51a0ff6ff9a935e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349471/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349471/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25487314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Savi, Monia</creatorcontrib><creatorcontrib>Rossi, Stefano</creatorcontrib><creatorcontrib>Bocchi, Leonardo</creatorcontrib><creatorcontrib>Gennaccaro, Laura</creatorcontrib><creatorcontrib>Cacciani, Francesca</creatorcontrib><creatorcontrib>Perotti, Alessio</creatorcontrib><creatorcontrib>Amidani, Davide</creatorcontrib><creatorcontrib>Alinovi, Rossella</creatorcontrib><creatorcontrib>Goldoni, Matteo</creatorcontrib><creatorcontrib>Aliatis, Irene</creatorcontrib><creatorcontrib>Lottici, Pier Paolo</creatorcontrib><creatorcontrib>Bersani, Danilo</creatorcontrib><creatorcontrib>Campanini, Marco</creatorcontrib><creatorcontrib>Pinelli, Silvana</creatorcontrib><creatorcontrib>Petyx, Marta</creatorcontrib><creatorcontrib>Frati, Caterina</creatorcontrib><creatorcontrib>Gervasi, Andrea</creatorcontrib><creatorcontrib>Urbanek, Konrad</creatorcontrib><creatorcontrib>Quaini, Federico</creatorcontrib><creatorcontrib>Buschini, Annamaria</creatorcontrib><creatorcontrib>Stilli, Donatella</creatorcontrib><creatorcontrib>Rivetti, Claudio</creatorcontrib><creatorcontrib>Macchi, Emilio</creatorcontrib><creatorcontrib>Mutti, Antonio</creatorcontrib><creatorcontrib>Miragoli, Michele</creatorcontrib><creatorcontrib>Zaniboni, Massimiliano</creatorcontrib><title>Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue</title><title>Particle and fibre toxicology</title><addtitle>Part Fibre Toxicol</addtitle><description>In light of recent developments in nanotechnologies, interest is growing to better comprehend the interaction of nanoparticles with body tissues, in particular within the cardiovascular system. Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Nanoparticles <50 nm in size are known to pass the alveolar-pulmonary barrier, enter into bloodstream and induce inflammation, but the direct pathogenic mechanisms still need to be evaluated. We thus focused our attention on titanium dioxide (TiO₂) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body.
We conducted functional studies on isolated adult rat cardiomyocytes exposed acutely in vitro to TiO₂ and on healthy rats administered a single dose of 2 mg/Kg TiO₂ NPs via the trachea. Transmission electron microscopy was used to verify the actual presence of TiO₂ nanoparticles within cardiac tissue, toxicological assays were used to assess lipid peroxidation and DNA tissue damage, and an in silico method was used to model the effect on action potential.
Ventricular myocytes exposed in vitro to TiO₂ had significantly reduced action potential duration, impairment of sarcomere shortening and decreased stability of resting membrane potential. In vivo, a single intra-tracheal administration of saline solution containing TiO₂ nanoparticles increased cardiac conduction velocity and tissue excitability, resulting in an enhanced propensity for inducible arrhythmias. Computational modeling of ventricular action potential indicated that a membrane leakage could account for the nanoparticle-induced effects measured on real cardiomyocytes.
Acute exposure to TiO₂ nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.</description><subject>Action Potentials - drug effects</subject><subject>Air Pollutants - toxicity</subject><subject>Animals</subject><subject>Arrhythmias, Cardiac - chemically induced</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Cells, Cultured</subject><subject>Computer Simulation</subject><subject>DNA Damage</subject><subject>Excitation Contraction Coupling - drug effects</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Heart Conduction System - drug effects</subject><subject>Heart Conduction System - physiopathology</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - physiopathology</subject><subject>Heart Ventricles - ultrastructure</subject><subject>Inhalation Exposure - adverse effects</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Male</subject><subject>Metal Nanoparticles - administration & dosage</subject><subject>Metal Nanoparticles - toxicity</subject><subject>Models, Biological</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - ultrastructure</subject><subject>Pollution</subject><subject>Rats, Wistar</subject><subject>Titanium - administration & dosage</subject><subject>Titanium - toxicity</subject><subject>Toxicity Tests, Acute</subject><issn>1743-8977</issn><issn>1743-8977</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNptkctqHDEQRYWJ8Sv5gGyCICsv2pZa6oc2AWMc22AI2M5a1KhLMxWmpUHS-PH36WFi44FQCxXSubdUXMa-SnEmZd-eZ1mb3lRC6kqIVlVqjx3JTquqN1336UN_yI5z_iOEavpGHrDDutF9p6Q-Yu6RCgRaj3yg-EID8gAhriAVckvMfJXiGAtySGnxWhYjQeZPBBwmPqErnELBBK5QDPyZyoInKNxBGggcL5TzGj-zfQ_LjF_-nSfs98-rx8ub6u7X9e3lxV3lGiFKZZToZxKcdnVXO6h9izPph6auFWioJbRCGC_MtIJX0mAjQXjfem_AqAaVOmE_tr6r9WzEwWEoCZZ2lWiE9GojkN19CbSw8_hktdJGd3Iy-L41mMMSLQUfJ8yNlJ29aJRpey36zZiz_1BTDTiSiwE9Tfc7gtMdwcQUfClzWOdsbx_ud1m5ZV2KOSf079-Xwm5Ct9vQ7RS63YRuN5pvH_d-V7ylrP4CFG6o_A</recordid><startdate>20141209</startdate><enddate>20141209</enddate><creator>Savi, Monia</creator><creator>Rossi, Stefano</creator><creator>Bocchi, Leonardo</creator><creator>Gennaccaro, Laura</creator><creator>Cacciani, Francesca</creator><creator>Perotti, Alessio</creator><creator>Amidani, Davide</creator><creator>Alinovi, Rossella</creator><creator>Goldoni, Matteo</creator><creator>Aliatis, Irene</creator><creator>Lottici, Pier Paolo</creator><creator>Bersani, Danilo</creator><creator>Campanini, Marco</creator><creator>Pinelli, Silvana</creator><creator>Petyx, Marta</creator><creator>Frati, Caterina</creator><creator>Gervasi, Andrea</creator><creator>Urbanek, Konrad</creator><creator>Quaini, Federico</creator><creator>Buschini, Annamaria</creator><creator>Stilli, Donatella</creator><creator>Rivetti, Claudio</creator><creator>Macchi, Emilio</creator><creator>Mutti, Antonio</creator><creator>Miragoli, Michele</creator><creator>Zaniboni, Massimiliano</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>5PM</scope></search><sort><creationdate>20141209</creationdate><title>Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue</title><author>Savi, Monia ; Rossi, Stefano ; Bocchi, Leonardo ; Gennaccaro, Laura ; Cacciani, Francesca ; Perotti, Alessio ; Amidani, Davide ; Alinovi, Rossella ; Goldoni, Matteo ; Aliatis, Irene ; Lottici, Pier Paolo ; Bersani, Danilo ; Campanini, Marco ; Pinelli, Silvana ; Petyx, Marta ; Frati, Caterina ; Gervasi, Andrea ; Urbanek, Konrad ; Quaini, Federico ; Buschini, Annamaria ; Stilli, Donatella ; Rivetti, Claudio ; Macchi, Emilio ; Mutti, Antonio ; Miragoli, Michele ; Zaniboni, Massimiliano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-9308b1ac4c272ca2f6eb1fd5223a4a21a6009f09851f319e51a0ff6ff9a935e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Action Potentials - 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Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Nanoparticles <50 nm in size are known to pass the alveolar-pulmonary barrier, enter into bloodstream and induce inflammation, but the direct pathogenic mechanisms still need to be evaluated. We thus focused our attention on titanium dioxide (TiO₂) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body.
We conducted functional studies on isolated adult rat cardiomyocytes exposed acutely in vitro to TiO₂ and on healthy rats administered a single dose of 2 mg/Kg TiO₂ NPs via the trachea. Transmission electron microscopy was used to verify the actual presence of TiO₂ nanoparticles within cardiac tissue, toxicological assays were used to assess lipid peroxidation and DNA tissue damage, and an in silico method was used to model the effect on action potential.
Ventricular myocytes exposed in vitro to TiO₂ had significantly reduced action potential duration, impairment of sarcomere shortening and decreased stability of resting membrane potential. In vivo, a single intra-tracheal administration of saline solution containing TiO₂ nanoparticles increased cardiac conduction velocity and tissue excitability, resulting in an enhanced propensity for inducible arrhythmias. Computational modeling of ventricular action potential indicated that a membrane leakage could account for the nanoparticle-induced effects measured on real cardiomyocytes.
Acute exposure to TiO₂ nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25487314</pmid><doi>10.1186/s12989-014-0063-3</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1743-8977 |
| ispartof | Particle and fibre toxicology, 2014-12, Vol.11 (1), p.63, Article 63 |
| issn | 1743-8977 1743-8977 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4349471 |
| source | Full-Text Journals in Chemistry (Open access); Publicly Available Content (ProQuest); PubMed Central |
| subjects | Action Potentials - drug effects Air Pollutants - toxicity Animals Arrhythmias, Cardiac - chemically induced Arrhythmias, Cardiac - physiopathology Cell Membrane Permeability - drug effects Cells, Cultured Computer Simulation DNA Damage Excitation Contraction Coupling - drug effects Health aspects Heart Heart Conduction System - drug effects Heart Conduction System - physiopathology Heart Ventricles - cytology Heart Ventricles - drug effects Heart Ventricles - physiopathology Heart Ventricles - ultrastructure Inhalation Exposure - adverse effects Lipid Peroxidation - drug effects Male Metal Nanoparticles - administration & dosage Metal Nanoparticles - toxicity Models, Biological Myocytes, Cardiac - cytology Myocytes, Cardiac - drug effects Myocytes, Cardiac - ultrastructure Pollution Rats, Wistar Titanium - administration & dosage Titanium - toxicity Toxicity Tests, Acute |
| title | Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue |
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