Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration

Golasik, Magdalena; Herman, Małgorzata; Olbert, Magdalena; Librowski, Tadeusz; Szklarzewicz, Janusz; Piekoszewski, Wojciech

doi:10.1016/j.toxlet.2016.02.009

Cited by 20 publications

(19 citation statements)

References 34 publications

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“…As mentioned above, nano‐TiO 2 are increasingly exposed to human beings by multiple routes. As soon as the nano‐TiO 2 traverse the various physiologic barriers into blood, the ECs lining the innermost layer of the cardiovascular system will be directly exposed to these NPs. The toxicities of nano‐TiO 2 exposure on the ECs are one of the most important approaches by which nano‐TiO 2 directly and/or indirectly affects the cardiovascular system.…”

Section: Discussionmentioning

confidence: 99%

“…With the increasing production and applications of nano‐TiO 2 , human exposure to these NPs continues to increase. Moreover, it has been reported that after inhalation, ingestion, or skin application, nano‐TiO 2 could penetrate rapidly into the systemic circulation and reach various organs, including liver, spleen, heart, kidney, and brain . where they could possibly pose adverse effects to these second target organs.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it has been reported that after inhalation, ingestion, or skin application, nano-TiO 2 could penetrate rapidly into the systemic circulation and reach various organs, including liver, spleen, heart, kidney, and brain. [15][16][17][18][19] where they could possibly pose adverse effects to these second target organs. After passage through the biological barriers, undoubtedly, nano-TiO 2 will inevitably end up in contact with the vascular endothelium and may induce cardiovascular damage before they reach other organs.…”

Section: Introductionmentioning

confidence: 99%

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The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Zeng

Feng

Wu-xiang

et al. 2018

Environmental Toxicology

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Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO ) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 μg/mL), all the four sizes of nano-TiO could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P < .05, P < .01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO , showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO -mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Zeng

Feng

Wu-xiang

et al. 2018

Environmental Toxicology

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“…In contrast to our findings, a previous study [1] demonstrated that TiO 2 is physiologically inactive exhibiting relatively low toxicity and considered unhazardous to humans. Many researchers [52][53][54] attributed these results to the very low and poor absorption of TiO 2 NPs after oral administration to rats so it should not result in excessive accumulation of metal in the organism. However, a previous study [55] stated that the toxicity of TiO 2 NPs is still controversial issue; the authors have reported significant adverse effects on in-vitro and in-vivo systems with higher toxicity for size decreasing NPs.…”

Section: Discussionmentioning

confidence: 99%

Effect of titanium dioxide nanoparticles on the spleen of adult male albino rats: Histological and immunohistochemical study

Ibrahim

Salem

Helal

et al. 2018

Egyptian Journal of Histology

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Introduction: Titanium dioxide nanoparticles (TiO 2 NPs) are commonly used in industry (e.g. cosmetics, sunscreens, food products, paints and drugs). But, they have different adverse cellular effects including oxidative stress and cellular damage. Aim of the work: To evaluate the possible toxic effect of titanium dioxide nanoparticles on the structure of the spleen of rats. Materials and Methods: Forty-five adult male rats were divided into three groups. Group I served as the control group. Group II (low-dose group) rats were given oral dose of TiO 2 (600 mg/kg/day) daily for 8 weeks. Group III (high-dose group) rats were given a daily oral dose of TiO 2 (1200 mg/kg/day) for 8 weeks. Spleen specimens were taken after 4 weeks, 8 weeks and 12 weeks from the start of the experiment. Thereafter, spleen specimens were processed for histological and immunohistochemical examinations. Results: The low-dose group showed slight disturbance in architecture of white pulp, slight congestion in red pulp and significant increase (P< 0.01) in CD4 and CD68 immuno-expression only after 8 week specimens compared with control group. The high-dose group showed marked disturbance in architecture of white pulp and significant increase (P< 0.01) in CD4 and CD68 immuno-expression after 4 week specimens, CD4 and CD68 immuno-expression significantly decreased (P< 0.01) in the 8 and in the 12 week specimens. No obvious improvement occurred after 12 weeks (withdrawal specimens). Conclusion: Prolonged exposure to daily high oral dose of TiO 2 NPs has deleterious and toxic effects on the spleen of rat, besides disruption of its structure.

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“…Furthermore, considerable evidence has supported that following skin application, ingestion, or inhalation, TiO 2 -NPs could rapidly penetrate the various physiological barriers into the systemic circulation and reach a range of secondary target organs, which include, but are not limited to, the heart, liver, lymph nodes, spleen, kidney, and the brain. [13][14][15][16][17][18] Undoubtedly, TiO 2 -NPs will inevitably end up in contact with the cardiovascular endothelium and may directly induce endothelial dysfunction and impairments and subsequently affect cardiovascular health before they reach other secondary organs. Hence, the potential risks of TiO 2 -NPs exposure on the cardiovascular health deserve great concern.…”

mentioning

confidence: 99%

The size‐dependent genotoxic potentials of titanium dioxide nanoparticles to endothelial cells

Liao

Chen

Liu

et al. 2019

Environmental Toxicology

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Despite intensive research activities, there are still many major knowledge gaps over the potential adverse effects of titanium dioxide nanoparticles (TiO2‐NPs), one of the most widely produced and used nanoparticles, on human cardiovascular health and the underlying mechanisms. In the present study, alkaline comet assay and cytokinesis‐block micronucleus test were employed to determine the genotoxic potentials of four sizes (100, 50, 30, and 10 nm) of anatase TiO2‐NPs to human umbilical vein endothelial cells (HUVECs) in culture. Also, the intracellular redox statuses were explored through the measurement of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. Meanwhile, the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) were also detected by western blot. The results showed that at the exposed levels (1, 5, and 25 μg/mL), all the four sizes of TiO2‐NPs could elicit an increase of both DNA damage and MN frequency in HUVECs in culture, with a positive dose‐dependent and negative size‐dependent effect relationship (T100 < T50 < T30 < T10). Also, increased levels of intracellular ROS, but decreased levels of GSH, were found in all the TiO2‐NP‐treated groups. Intriguingly, a very similar manner of dose‐dependent and size‐dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also elevated in the TiO2‐NP‐exposed HUVECs, with an inversely size‐dependent effect relationship. These findings indicated that induction of oxidative stress and subsequent genotoxicity might be an important biological mechanism by which TiO2‐NP exposure would cause detrimental effects to human cardiovascular health.

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Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration

Cited by 20 publications

References 34 publications

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Effect of titanium dioxide nanoparticles on the spleen of adult male albino rats: Histological and immunohistochemical study

The size‐dependent genotoxic potentials of titanium dioxide nanoparticles to endothelial cells

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