Dataset Information

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

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 <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 (TiO?) 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 TiO? and on healthy rats administered a single dose of 2 mg/Kg TiO? NPs via the trachea. Transmission electron microscopy was used to verify the actual presence of TiO? 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 TiO? 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 TiO? 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 TiO? nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events.

SUBMITTER: Savi M

PROVIDER: S-EPMC4349471 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Savi Monia M Rossi Stefano S Bocchi Leonardo L Gennaccaro Laura L Cacciani Francesca F Perotti Alessio A Amidani Davide D Alinovi Rossella R Goldoni Matteo M Aliatis Irene I Lottici Pier Paolo PP Bersani Danilo D Campanini Marco M Pinelli Silvana S Petyx Marta M Frati Caterina C Gervasi Andrea A Urbanek Konrad K Quaini Federico F Buschini Annamaria A Stilli Donatella D Rivetti Claudio C Macchi Emilio E Mutti Antonio A Miragoli Michele M Zaniboni Massimiliano M

Particle and fibre toxicology 20141209

<h4>Background</h4>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 ev ...[more]

PMID: 25487314

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Project description:Nanoparticles (NPs), materials that have one dimension less than 100 nm, are used in manufacturing, health, and food products, and consumer products including cosmetics, clothing, and household appliances. Their utility to industry is derived from their high surface-area-to-volume ratios and physico-chemical properties distinct from their bulk counterparts, but the near-certainty that NPs will be released into the environment raises the possibility that they could present health risks to humans and wildlife. The thyroid hormones (THs), thyroxine, and 3,3',5-triiodothyronine (T3), are involved in development and metabolism in vertebrates including humans and frogs. Many of the processes of anuran metamorphosis are analogous to human post-embryonic development and disruption of TH action can have drastic effects. These shared features make the metamorphosis of anurans an excellent model for screening for endocrine disrupting chemicals (EDCs). We used the cultured tailfin (C-fin) assay to examine the exposure effects of 0.1-10 nM (~8-800 ng/L) of three types of ~20 nm TiO2 NPs (P25, M212, M262) and micron-sized TiO2 (μ TiO2) ±10 nM T3. The actual Ti levels were 40.9-64.7% of the nominal value. Real-time quantitative polymerase chain reaction (QPCR) was used to measure the relative amounts of mRNA transcripts encoding TH-responsive THs receptors (thra and thrb) and Rana larval keratin type I (rlk1), as well as the cellular stress-responsive heat shock protein 30 kDa (hsp30), superoxide dismutase (sod), and catalase (cat). The levels of the TH-responsive transcripts were largely unaffected by any form of TiO2. Some significant effects on stress-related transcripts were observed upon exposure to micron-sized TiO2, P25, and M212 while no effect was observed with M262 exposure. Therefore, the risk of adversely affecting amphibian tissue by disrupting TH-signaling or inducing cellular stress is low for these compounds relative to other previously-tested NPs.

Project description:BackgroundNon-communicable diseases, intended as the results of a combination of inherited, environmental and biological factors, kill 40 million people each year, equivalent to roughly 70% of all premature deaths globally. The possibility that manufactured nanoparticles (NPs) may affect cardiac performance, has led to recognize NPs-exposure not only as a major Public Health concern, but also as an occupational hazard. In volunteers, NPs-exposure is problematic to quantify. We recently found that inhaled titanium dioxide NPs, one of the most produced engineered nanomaterials, acutely increased cardiac excitability and promoted arrhythmogenesis in normotensive rats by a direct interaction with cardiac cells. We hypothesized that such scenario can be exacerbated by latent cardiovascular disorders such as hypertension.ResultsWe monitored cardiac electromechanical performance in spontaneously hypertensive rats (SHRs) exposed to titanium dioxide NPs for 6 weeks using a combination of cardiac functional measurements associated with toxicological, immunological, physical and genetic assays. Longitudinal radio-telemetry ECG recordings and multiple-lead epicardial potential mapping revealed that atrial activation times significantly increased as well as proneness to arrhythmia. At the third week of nanoparticles administration, the lung and cardiac tissue encountered a maladaptive irreversible structural remodelling starting with increased pro-inflammatory cytokines levels and lipid peroxidation, resulting in upregulation of the main pro-fibrotic cardiac genes. At the end of the exposure, the majority of spontaneous arrhythmic events terminated, while cardiac hemodynamic deteriorated and a significant accumulation of fibrotic tissue occurred as compared to control untreated SHRs. Titanium dioxide nanoparticles were quantified in the heart tissue although without definite accumulation as revealed by particle-induced X-ray emission and ultrastructural analysis.ConclusionsThe co-morbidity of hypertension and inhaled nanoparticles induces irreversible hemodynamic impairment associated with cardiac structural damage potentially leading to heart failure. The time-dependence of exposure indicates a non-return point that needs to be taken into account in hypertensive subjects daily exposed to nanoparticles.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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