Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue

Monia Savi, Stefano Rossi, Leonardo Bocchi, Laura Gennaccaro, Francesca Cacciani, Alessio Perotti, Davide Amidani, Rossella Alinovi, Matteo Goldoni, Irene Aliatis, Pier Paolo Lottici, Danilo Bersani, Marco Campanini, Silvana Pinelli, Marta Petyx, Caterina Frati, Andrea Gervasi, Konrad Urbanek, Federico Quaini, Annamaria BuschiniDonatella Stilli, Claudio Rivetti, Emilio Macchi, Antonio Mutti, Michele Miragoli, Massimiliano Zaniboni

Research output: Contribution to journalArticle

Abstract

Background: 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 2) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body. Methods: 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. Results: 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. Conclusions: Acute exposure to TiO2 nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalParticle and Fibre Toxicology
DOIs
Publication statusAccepted/In press - Dec 9 2014

Fingerprint

Nanoparticles
Rats
Cardiac Arrhythmias
Tissue
Action Potentials
Cardiac Myocytes
Membranes
Cardiovascular system
Sarcomeres
Environmental Pollution
Nanotechnology
Nanostructures
Cardiovascular System
titanium dioxide
Trachea
Transmission Electron Microscopy
Human Body
Nanostructured materials
Sodium Chloride
Computer Simulation

Keywords

  • Cardiac arrhythmia
  • Experimental model
  • Membrane leakage
  • Pollution
  • Supernormal conduction
  • Titanium dioxide nanoparticles

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Savi, M., Rossi, S., Bocchi, L., Gennaccaro, L., Cacciani, F., Perotti, A., ... Zaniboni, M. (Accepted/In press). Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue. Particle and Fibre Toxicology, 1-16. https://doi.org/10.1186/s12989-014-0063-3

Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue. / 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.

In: Particle and Fibre Toxicology, 09.12.2014, p. 1-16.

Research output: Contribution to journalArticle

Savi, M, Rossi, S, Bocchi, L, Gennaccaro, L, Cacciani, F, Perotti, A, Amidani, D, Alinovi, R, Goldoni, M, Aliatis, I, Lottici, PP, Bersani, D, Campanini, M, Pinelli, S, Petyx, M, Frati, C, Gervasi, A, Urbanek, K, Quaini, F, Buschini, A, Stilli, D, Rivetti, C, Macchi, E, Mutti, A, Miragoli, M & Zaniboni, M 2014, 'Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue', Particle and Fibre Toxicology, pp. 1-16. https://doi.org/10.1186/s12989-014-0063-3
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. / Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue. In: Particle and Fibre Toxicology. 2014 ; pp. 1-16.
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AU - Savi, Monia

AU - Rossi, Stefano

AU - Bocchi, Leonardo

AU - Gennaccaro, Laura

AU - Cacciani, Francesca

AU - Perotti, Alessio

AU - Amidani, Davide

AU - Alinovi, Rossella

AU - Goldoni, Matteo

AU - Aliatis, Irene

AU - Lottici, Pier Paolo

AU - Bersani, Danilo

AU - Campanini, Marco

AU - Pinelli, Silvana

AU - Petyx, Marta

AU - Frati, Caterina

AU - Gervasi, Andrea

AU - Urbanek, Konrad

AU - Quaini, Federico

AU - Buschini, Annamaria

AU - Stilli, Donatella

AU - Rivetti, Claudio

AU - Macchi, Emilio

AU - Mutti, Antonio

AU - Miragoli, Michele

AU - Zaniboni, Massimiliano

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N2 - Background: 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 2) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body. Methods: 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. Results: 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. Conclusions: Acute exposure to TiO2 nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.

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KW - Pollution

KW - Supernormal conduction

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