scholarly journals Lack of pulmonary fibrogenicity and carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model

2021 ◽  
Author(s):  
Shotaro Yamano ◽  
Tomoki Takeda ◽  
Yuko Goto ◽  
Shigeyuki Hirai ◽  
Yusuke Furukawa ◽  
...  

Background: With the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. There have been no systemic inhalation exposure studies of titanium dioxide nanoparticles (TiO2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) 26-week study mice model for detecting carcinogenicity. Methods: Male and female rasH2 mice were exposed to 2, 8 or 32 mg/m3 of TiO2 NPs for 6 hours/day, 5 days/week for 26 weeks using a whole-body inhalation exposure system, with reference to the Organization for Economic Co-operation and Development principles of Good Laboratory Practice. All tissues including lungs, and blood were collected and subjected to biological and histopathological analyses. Additionally, Ki67 positive index were evaluated in mice lung alveolar epithelial type 2 cell (AEC2). Results: This study established a stable method for generating and exposing TiO2 NPs aerosol, and clarified the dose-response relationship by TiO2 NPs inhalation to rasH2 mice. TiO2 NPs exposure induced deposition of particles in lungs and mediastinal lymph nodes in a dose-dependent manner in each exposure group. Additionally, alveolar inflammation was only observed in 32 mg/m3 exposure group in both the sexes. Exposure to TiO2 NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of AEC2 was examined, and it was not increased by exposure to TiO2 NPs. Conclusions: This is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m3, which is considered to be a high concentration. Macrophages undergoing phagocytosis due to TiO2 NPs exposure formed inflammatory foci in the alveolar regions of exposed mice but did not develop fibrosis or hyperplasia or tumors. Moreover, the cell proliferative ability of AEC2 in lesions was not increased. In addition, no carcinogenicity was observed for any organs other than the lungs in this study.

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4090
Author(s):  
Morteza Sheikhalipour ◽  
Behrooz Esmaielpour ◽  
Gholamreza Gohari ◽  
Maryam Haghighi ◽  
Hessam Jafari ◽  
...  

High salt levels are one of the significant and major limiting factors on crop yield and productivity. Out of the available attempts made against high salt levels, engineered nanoparticles (NPs) have been widely employed and considered as effective strategies in this regard. Of these NPs, titanium dioxide nanoparticles (TiO2 NPs) and selenium functionalized using chitosan nanoparticles (Cs–Se NPs) were applied for a quite number of plants, but their potential roles for alleviating the adverse effects of salinity on stevia remains unclear. Stevia (Stevia rebaudiana Bertoni) is one of the reputed medicinal plants due to their diterpenoid steviol glycosides (stevioside and rebaudioside A). For this reason, the current study was designed to investigate the potential of TiO2 NPs (0, 100 and 200 mg L−1) and Cs–Se NPs (0, 10 and 20 mg L−1) to alleviate salt stress (0, 50 and 100 mM NaCl) in stevia. The findings of the study revealed that salinity decreased the growth and photosynthetic traits but resulted in substantial cell damage through increasing H2O2 and MDA content, as well as electrolyte leakage (EL). However, the application of TiO2 NPs (100 mg L−1) and Cs–Se NPs (20 mg L−1) increased the growth, photosynthetic performance and activity of antioxidant enzymes, and decreased the contents of H2O2, MDA and EL under the saline conditions. In addition to the enhanced growth and physiological performance of the plant, the essential oil content was also increased with the treatments of TiO2 (100 mg L−1) and Cs–Se NPs (20 mg L−1). In addition, the tested NPs treatments increased the concentration of stevioside (in the non-saline condition and under salinity stress) and rebaudioside A (under the salinity conditions) in stevia plants. Overall, the current findings suggest that especially 100 mg L−1 TiO2 NPs and 20 mg L−1 Cs–Se could be considered as promising agents in combating high levels of salinity in the case of stevia.


Nanoscale ◽  
2020 ◽  
Author(s):  
Yanjun Gao ◽  
Tingyu Li ◽  
Shuming Duan ◽  
Lizhi Lv ◽  
Yuan Li ◽  
...  

Titanium dioxide nanoparticles (TiO2-NPs) is widely applicated as additives in foods for its excellent whitening and brightening capability. Although the toxicity and antibacterial activity of TiO2-NPs has been extensively studied,...


Author(s):  
Wei Zhang ◽  
Jinghua Long ◽  
Jianmin Geng ◽  
Jie Li ◽  
Zhongyi Wei

The impact of engineered nanoparticles (ENPs) on the migration and toxicity of coexisting pollutants is still unclear, especially in soil media. This study aims to evaluate the impact of titanium dioxide nanoparticles (TiO2 NPs) on the phytotoxicity of cadmium (Cd) to Oryza sativa L., and the migration of cadmium (Cd) in the soil-rice system. Three different Cd stress groups (C1 group: 1.0 mg kg−1, C2 group: 2.5 mg kg−1 and C3 group: 5.0 mg kg−1) were set in the pot experiment, and the target concentration of TiO2 NPs in each group were 0 mg kg−1 (T0), 50 mg kg−1 (T1), 100 mg kg−1 (T2) and 500 mg kg−1 (T3). Plant height and biomass decreased with the increasing of Cd content in paddy soil. TiO2 NPs could lower the phytotoxicity of Cd in terms of the changes in the morphological and biochemical characteristics, especially in the tillering and booting stage. In the tillering stage, TiO2 NPs addition caused a significant increase in plant height, biomass and the total chlorophyll content in the leaves of Oryza saliva L. In the booting stage, TiO2 NPs addition caused a 15% to 32% and 24% to 48% reduction of malondialdehyde (MDA) content for the C2 and C3 group, respectively, compared to that of the respective control treatment (T0). TiO2-NPs addition reduced the activity of peroxidase (POD) in the leaves in the booting and heading stage, and the activity of catalase (CAT) in the tillering stage. In the C1 and C2 group, the grain Cd content in the 100 and 500 mg kg−1 TiO2 NPs treatments reached 0.47–0.84 mg kg−1, obviously higher than that of the treatment without TiO2 NPs (0.27–0.32 mg kg−1), suggesting that TiO2-NPs could promote Cd migration in the soil-rice system.


2009 ◽  
Vol 189 ◽  
pp. S186 ◽  
Author(s):  
Kyuhong Lee ◽  
Young-Su Yang ◽  
Soon-Jin Kwon ◽  
Jin-Su Lee ◽  
Seung-Jin Choi ◽  
...  

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1955 ◽  
Author(s):  
Elizabeth Huerta-García ◽  
Iván Zepeda-Quiroz ◽  
Helen Sánchez-Barrera ◽  
Zaira Colín-Val ◽  
Ernesto Alfaro-Moreno ◽  
...  

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.


Author(s):  
Daniel Ziental ◽  
Beata Czarczynska-Goslinska ◽  
Dariusz T. Mlynarczyk ◽  
Arleta Glowacka-Sobotta ◽  
Beata Stanisz ◽  
...  

Metallic nanoparticles (NPs), among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in the novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites with other molecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 NPs, leading to hybrid materials. These nanostructures can reveal increased light absorption allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer therapy, many approaches utilizing titanium dioxide were tested. The most significant studies are discussed in this review.


Author(s):  
Clarisse Liné ◽  
Juan Reyes-Herrera ◽  
Mansi Bakshi ◽  
Mohammad Wazne ◽  
Valentin Costa ◽  
...  

Carbon nanotubes (CNTs) and titanium dioxide nanoparticles (TiO2-NPs) are among the most used nanomaterials (NMs). However, their impacts especially on the terrestrial ecosystems and on plants are still controversial. Apart...


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