Objective. The effect of TiO2 NP exposure on the nervous system and the underlying mechanism remain unclear. The antioxidant effect of TiO2 NPs at a low dose was newly found in our study, which was different from the effect at high dose. This study is aimed at exploring the mechanism underlying the antioxidant effects of TiO2 NPs at low dose and the induction of ROS accumulation by TiO2 NPs at high dose in neurogenic cell lines. Methods. We measured the changes in key molecules in the ROS regulation pathway by western blotting, flow cytometry, and commercial assay kits, and these key molecules were further evaluated to verify their interactions and roles using SH-SY5Y, U251, and SK-N-SH cell lines treated with TiO2 NPs. Results. Our results showed that the weak antioxidant effect at low dose was caused by mTOR/GCLc-induced GSH overproduction and GSH-Px activity impairment. ROS accumulation at high dose was caused by a mTOR/GCLc-mediated decrease in GSH production, GSH-Px activity impairment, and dramatic ROS production. Furthermore, we found that the ROS species were mainly O2-⋅, and that SOD played a crucial role in reducing O2-⋅ levels before the mTOR protein was activated. Conclusion. We revealed the mechanism underlying the bidirectional regulation of ROS induced by TiO2 NPs at different doses in neurogenic cell lines. Our study emphasized the potential neurotoxic effects of NPs at low dose, which should arouse concern about their safety.

/pdf/the-mtor-gclc-gsh-pathway-mediates-the-dose-dependent-4t1gpubejw.pdf

The mTOR/GCLc/GSH Pathway Mediates the Dose-Dependent Bidirectional Regulation of ROS Induced by TiO2 NPs in Neurogenic Cells

Given the global abundance and environmental persistence, exposure of humans and (aquatic) animals to micro- and nanoplastics is unavoidable. Current evidence indicates that micro- and nanoplastics can be taken up by aquatic organism as well as by mammals. Upon uptake, micro- and nanoplastics can reach the brain, although there is limited information regarding the number of particles that reaches the brain and the potential neurotoxicity of these small plastic particles. Earlier studies indicated that metal and metal-oxide nanoparticles, such as gold (Au) and titanium dioxide (TiO2) nanoparticles, can also reach the brain to exert a range of neurotoxic effects. Given the similarities between these chemically inert metal(oxide) nanoparticles and plastic particles, this review aims to provide an overview of the reported neurotoxic effects of micro- and nanoplastics in different species and in vitro. The combined data, although fragmentary, indicate that exposure to micro- and nanoplastics can induce oxidative stress, potentially resulting in cellular damage and an increased vulnerability to develop neuronal disorders. Additionally, exposure to micro- and nanoplastics can result in inhibition of acetylcholinesterase activity and altered neurotransmitter levels, which both may contribute to the reported behavioral changes. Currently, a systematic comparison of the neurotoxic effects of different particle types, shapes, sizes at different exposure concentrations and durations is lacking, but urgently needed to further elucidate the neurotoxic hazard and risk of exposure to micro- and nanoplastics.

/pdf/the-plastic-brain-neurotoxicity-of-micro-and-nanoplastics-4u3isk0ga2.pdf

The plastic brain: neurotoxicity of micro- and nanoplastics

Research links air pollution mostly to respiratory and cardiovascular disease. The effects of air pollution on the central nervous system (CNS) are not broadly recognized. Urban outdoor pollution is a global public health problem particularly severe in megacities and in underdeveloped countries, but large and small cities in the United States and the United Kingom are not spared. Fine and ultrafine particulate matter (UFPM) defined by aerodynamic diameter (<2.5-μm fine particles, PM2.5, and <100-nm UFPM) pose a special interest for the brain effects given the capability of very small particles to reach the brain. In adults, ambient pollution is associated to stroke and depression, whereas the emerging picture in children show significant systemic inflammation, immunodysregulation at systemic, intratechal and brain levels, neuroinflammation and brain oxidative stress, along with the main hallmarks of Alzheimer and Parkinson's diseases: hyperphosphorilated tau, amyloid plaques and misfolded α-synuclein. Animal models exposed to particulate matter components show markers of both neuroinflammation and neurodegeneration. Epidemiological, cognitive, behavioral and mechanistic studies into the association between air pollution exposures and the development of CNS damage particularly in children are of pressing importance for public health and quality of life. Primary health providers have to include a complete prenatal and postnatal environmental and occupational history to indoor and outdoor toxic hazards and measures should be taken to prevent or reduce further exposures.

/pdf/air-pollution-and-your-brain-what-do-you-need-to-know-right-a2uw1tenkt.pdf

Air pollution and your brain: what do you need to know right now.

Titanium dioxide (TiO2 ) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano-TiO2 ) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano-TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano-TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano-TiO2 as a non-sensitizer and as mild- or non-irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano-TiO2 . According to the SCCS, nano-TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano-TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano-TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano-TiO2 absorption and toxicity are limited. The incidental oral exposure to nano-TiO2 contained in lip balms is thus not expected to induce adverse health effects.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.15943

Safety of titanium dioxide nanoparticles in cosmetics

Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications

Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO2 nanoparticles

Exposure to lanthanoids (Ln) elicits an adverse response such as oxidative injury of lung in animals and human. The molecular targets of Ln remain unclear. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in LaCl3 -induced oxidative stress in mouse lung were investigated. Mice were exposed to 2, 5, and 10 mg/kg body weight by nasal administration for 6 consecutive months. With increased doses, La was markedly accumulated and promoted the reactive oxygen species (ROS) production in the lung, which in turn resulted in peroxidation of lipids, proteins and DNA, and severe pulmonary damages. Furthermore, LaCl3 exposure could significantly increase levels of Nrf2, heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC) expressions in the LaCl3 -exposed lung. These findings imply that the induction of Nrf2 expression is an adaptive intracellular response to LaCl3 -induced oxidative stress in mouse lung, and that Nrf2 may regulate the LaCl3 -induced pulmonary damages.

Molecular mechanism of oxidative damage of lung in mice following exposure to lanthanum chloride.

http://www.cell.com/article/S2372770522001012/pdf

Xuecen Wang

Papers

Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO2 nanoparticles

Molecular mechanism of oxidative damage of lung in mice following exposure to lanthanum chloride.

Stabilization of DEPTOR sensitizes hypopharyngeal cancer to radiotherapy via targeting degradation