Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissueReport as inadecuate

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Particle and Fibre Toxicology

, 11:63

First Online: 09 December 2014Received: 28 May 2014Accepted: 06 November 2014


BackgroundIn 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.

MethodsWe 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.

ResultsVentricular 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.

ConclusionsAcute exposure to TiO2 nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.

KeywordsPollution Cardiac arrhythmia Experimental model Titanium dioxide nanoparticles Supernormal conduction Membrane leakage AbbreviationsTiO2Titanium dioxide


NIOSHNational Institute of Occupation Safety and Health

APAction potential

APDAction potential duration

APAAction potential amplitude

UPSAction potential upstroke

ROSReactive oxygen species

AFMAtomic force microscopy

VmTransmembrane potential

VrResting potential

CmMembrane capacitance

RmMembrane resistance

CTRLControl non-exposed cells

NPCTiO2-exposed cells

NPRTiO2-exposed rats

TBARSThiobarbituric acid reactive substance

CVCoefficient of variability

RVRight ventricle

LVLeft ventricle

SCsSpontaneous contractions

CVtTransverse conduction velocity

CVlLongitudinal conduction velocity

ERPEffective refractory period

SCGESingle-cell gel electrophoresis

TEMTransmission electron microscopy

FSFraction of shortening

Electronic supplementary materialThe online version of this article doi:10.1186-s12989-014-0063-3 contains supplementary material, which is available to authorized users.

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Author: Monia Savi - Stefano Rossi - Leonardo Bocchi - Laura Gennaccaro - Francesca Cacciani - Alessio Perotti - Davide Amidani - R

Source: https://link.springer.com/

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