Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.
TL;DR: A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles.
Abstract: Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.
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TL;DR: An assessment of signaling pathways that are involved in the nanoparticle-induced oxidative stress and propose possible strategies to circumvent nanotoxicity are provided.
Abstract: Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins)-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB) signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo. In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.
365 citations
Cites background from "Effects of sub-acute exposure to Ti..."
...These nanoparticles accumulated in the brain and caused axillary toxicity, disrupting normal metabolism of neurotransmitters and ultimately leading to brain damage [47]....
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TL;DR: The mechanism underlying the bidirectional regulation of ROS induced by TiO2 NPs at different doses in neurogenic cell lines was revealed and the potential neurotoxic effects of NPs should be emphasized, which should arouse concern about their safety.
Abstract: 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.
223 citations
Cites background from "Effects of sub-acute exposure to Ti..."
...the overproduction of reactive oxygen species (ROS) and eventually affecting brain function [8, 9]....
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TL;DR: In most studies, TiO2 nanoparticles appeared to have caused oxidative stress, histopathological alterations, carcinogenesis, genotoxicity and immune disruption, so the use of such materials in humans must be either avoided or strictly managed to minimise risks for human health in various situations.
Abstract: Nano-titanium dioxide (TiO2) is one of the most commonly used materials being synthesized for use as one of the top five nanoparticles. Due to the extensive application of TiO2 nanoparticles and their inclusion in many commercial products, the increased exposure of human beings to nanoparticles is possible. This exposure could be routed via dermal penetration, inhalation and oral ingestion or intravenous injection. Therefore, regular evaluation of their potential toxicity and distribution in the bodies of exposed individuals is essential. Keeping in view the potential health hazards of TiO2 nanoparticles for humans, we reviewed the research articles about studies performed on rats or other mammals as animal models. Most of these studies utilized the dermal or skin and the pulmonary exposures as the primary routes of toxicity. It was interesting that only very few studies revealed that the TiO2 nanoparticles could penetrate through the skin and translocate to other tissues, while many other studies demonstrated that no penetration or translocation could happen through the skin. Conversely, the TiO2 nanoparticles that entered through the pulmonary route were translocated to the brain or the systemic circulation from where these reached other organs like the kidney, liver, etc. In most studies, TiO2 nanoparticles appeared to have caused oxidative stress, histopathological alterations, carcinogenesis, genotoxicity and immune disruption. Therefore, the use of such materials in humans must be either avoided or strictly managed to minimise risks for human health in various situations.
212 citations
TL;DR: 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.
Abstract: 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.
207 citations
TL;DR: This review advocates revisiting the current safety and regulation of specific sunscreens and investing in alternative UV protection technologies, including zinc oxide and titanium dioxide.
Abstract: Sunscreen application is the main strategy used to prevent the maladies inflicted by ultraviolet (UV) radiation Despite the continuously increasing frequency of sunscreen use worldwide, the prevalence of certain sun exposure-related pathologies, mainly malignant melanoma, is also on the rise In the past century, a variety of protective agents against UV exposure have been developed Physical filters scatter and reflect UV rays and chemical filters absorb those rays Alongside the evidence for increasing levels of these agents in the environment, which leads to indirect exposure of wildlife and humans, recent studies suggest a toxicological nature for some of these agents Reviews on the role of these agents in developmental and endocrine impairments (both pathology and related mechanisms) are based on both animal and human studies, yet information regarding the potential neurotoxicity of these agents is scant In this review, data regarding the neurotoxicity of several organic filters: octyl methoxycinnamate, benzophenone-3 and -4, 4-methylbenzylidene camphor, 3-benzylidene camphor and octocrylene, and two allowed inorganic filters: zinc oxide and titanium dioxide, is presented and discussed Taken together, this review advocates revisiting the current safety and regulation of specific sunscreens and investing in alternative UV protection technologies
175 citations
Cites background from "Effects of sub-acute exposure to Ti..."
...Oral ZnO NPs (500 mg/ kg) administration for 21 consecutive days resulted in elevated ROS levels and altered antioxidants: glutathione (GSH) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione Stransferase activity (GST), in both the brain and liver of male Swiss albino mice [95]....
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...after oral administration for 21 days (500 mg/kg) [95]....
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...Combined with increased DA and NE levels in the cerebral cortex, these results suggest a neurotoxic potential for ZnO NPs [95]....
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References
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24,847 citations
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TL;DR: The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
Abstract: Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
8,323 citations
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