Abstract
Titanium dioxide nanoparticles (TiO2 NPs) are widely used in industry and daily life. TiO2 NPs can penetrate into the body, translocate from the lungs into the circulation and come into contact with cardiac cells. In this work, we evaluated the toxicity of TiO2 NPs on H9c2 rat cardiomyoblasts. Internalization of TiO2 NPs and their effect on cell proliferation, viability, oxidative stress and cell death were assessed, as well as cell cycle alterations. Cellular uptake of TiO2 NPs reduced metabolic activity and cell proliferation and increased oxidative stress by 19-fold measured as H2DCFDA oxidation. TiO2 NPs disrupted the plasmatic membrane integrity and decreased the mitochondrial membrane potential. These cytotoxic effects were related with changes in the distribution of cell cycle phases resulting in necrotic death and autophagy. These findings suggest that TiO2 NPs exposure represents a potential health risk, particularly in the development of cardiovascular diseases via oxidative stress and cell death.
Highlights
Titanium dioxide nanoparticles (TiO2 NPs) are widely used in foods, medicines, and cosmetics [1].Human exposure occurs either by oral, dermal or inhalation routes [2]
In order to corroborate this, H9c2 cells were exposed to 5 μg/cm2 TiO2 NPs for 24 h and were analyzed by transmission electron microscopy (TEM)
Numerous nanoparticle aggregates with size < 500 nm were observed inside cells (Figure 1B); large aggregates > 2 μM were present (Figure 1C,D)
Summary
Titanium dioxide nanoparticles (TiO2 NPs) are widely used in foods, medicines, and cosmetics [1]. In mice instilled intratracheally with low (18 μg) and high (162 μg) TiO2 NPs doses, these nanoparticles were accumulated in heart and liver and translocated into circulation 24 h after exposure [4]. Abdominal injection of TiO2 NPs in mice caused titanium accumulation in several organs, seriously damaging the liver, kidneys and heart and altering blood sugar and lipids [6]. Since TiO2 NPs can translocate into the systemic circulation and the heart [4], we hypothesized that these nanoparticles could induce damage to cardiac cells. To test this hypothesis, we exposed H9c2 cells to TiO2 NPs and examined their effects on cell cycle phases, mitochondrial function, oxidative stress, cell death and autophagy
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