Toxicity Of TiO2 Nanoparticles Research Articles

Physiological and transcriptomic analysis reveals the toxic and protective mechanisms of marine microalga Chlorella pyrenoidosa in response to TiO2 nanoparticles and UV-B radiation

Concerns have been raised regarding the adverse effects of nanoparticles (NPs) on marine organisms, as an increasing number of NPs inevitably enter the marine environment with the development of nanotechnology. Owing to the photocatalytic properties, TiO2 NPs' toxicity may be aggravated by enhanced UV-B resulting from stratospheric ozone depletion. However, the molecular mechanisms of phytoplankton in response to TiO2 NPs under UV-B remains poorly understood. In this study, we integrated whole transcriptome analysis with physiological data to provide understanding on the toxic and protective mechanisms of marine Chlorella pyrenoidosa in response to TiO2 NPs under UV-B. The results indicated that the changes in gene expression could be related to the growth inhibition and TiO2 NP internalization in C. pyrenoidosa, and several molecular mechanisms were identified as toxicity response to TiO2 NPs and UV-B. Differential expression of genes involved in glycerophospholipids metabolism indicated that cell membrane disruption allowed TiO2 NPs to enter the algal cell under UV-B exposure, although the up-regulation of genes involved in the general secretory dependent pathway and the ATP-binding cassette transporter family drove cellular secretion of extracellular polymeric substances, acting as a barrier that prevent TiO2 NP internalization. The absence of changes in gene expression related to the antioxidant system may be responsible for the severe oxidative stress observed in algal cells following exposure to TiO2 NPs under UV-B irradiation. Moreover, differential expression of genes involved in pathways such as photosynthesis and energy metabolism were up-regulated, including the light-harvesting, photosynthetic electron transport coupled to photophosphorylation, carbon fixation, glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that more energy and metabolites were supplied to cope with the toxicity of TiO2 NPs and UV-B. The obtained results provide valuable information on the molecular mechanisms of response of marine phytoplankton exposed to TiO2 NPs and UV-B.

Exposure concentration ratios and biological responses play a critical role in determining the joint toxicity of TiO2 nanoparticles and As(V) to the organism: The case study in marine algae Phaeodactylum tricornutum

Environmental risks of manufactured nanomaterials (MNMs) have been widely investigated while the understanding for joint toxicity mechanism of MNMs with other contaminants is still limited. This limitation may be attributed to variations in the concentration ratios of MNMs and co-existing contaminants in the real environment. To better assess the joint toxicity and clarify its underlying mechanisms, this study exposed Phaeodactylum tricornutum to different concentration combinations of nano-sized titanium dioxide (nTiO2) and As(V) at toxic unit (TU) ratios of 1:4,1:1, and 4:1. The results demonstrated that the joint toxicity modes of nTiO2 and As(V) varied with the TU ratios exhibiting synergism for 1:4, partially addition for 1:1, and antagonism for 4:1. Specifically, at low TU ratio of 1:4, the adsorption of As(V) by nTiO2 together with the subsequent internalization of nTiO2 promoted a significant enrichment of As in algae. Simultaneously, the up-regulation of pst (phosphate transporter) genes in charge of the As(V) transport molecular further exacerbated the enrichment of inorganic As in algae, while the down-regulation of ArsM (arsenite S-adenosylmethionine methyltransferases) genes in charge of the As metabolism inhibited As biotransformation from toxic inorganic to nontoxic organic, causing the aggravated accumulation of toxic inorganic As in algae. At higher TU ratios of 1:1 and 4:1, the accumulation of As decreased in algae due to the higher sedimentation of nTiO2 and thus the lower internalization of As-adsorbed nTiO2, as well as the down-regulation of pst genes restricting the transportation of As(V) into algal cells, which jointly accelerated the As biotransformation from toxic inorganic to nontoxic organic. Our results suggest that more attention should be paid to exposure concentration ratios of MNMs and co-existing contaminants and biological responses including bioavailability, bioaccumulation, biotransformation, which would play a critical role in determining the joint toxicity to the organism.

Potential and Harmful Effects of Titanium Dioxide Nanoparticle on Health: A Brief Note

Abstract: Titanium dioxide nanoparticles (TiO2 NPs) are formed in vast amounts worldwide for usage in several applications. They possess excellent photocatalytic properties, high chemical stability, and a wide bandgap, making them highly effective in environmental remediation and solar energy conversion. TiO2 nanoparticles exhibit biocompatibility, allowing their utilization in biomedical uses, such as molecular imaging, drug delivery, and tissue engineering. Chemical methods, such as hydrothermal, sol-gel, and chemical vapor deposition, provide versatility in controlling nanoparticle size, morphology, and crystallinity. They offer relatively lower production costs, scalability, and the ability to incorporate dopants or functionalize the nanoparticle surface. Their small size and large surface area-to-volume ratio enable enhanced reactivity and surface functionality, facilitating their incorporation into composite materials and surface coatings for improved performance. Regarding the potential toxicity of TiO2 nanoparticles, the bulk form of TiO2 is considered safe for human consumption, but the reduced size of nanoparticles raises concerns about their potential adverse effects. TiO2 nanoparticles strongly depend on factors, such as particle size, surface modifications, exposure route, and duration. Therefore, continued research is essential to gain a comprehensive understanding of the toxicity mechanisms and develop strategies to mitigate any potential adverse effects, ensuring the safe and responsible utilization of TiO2 nanoparticles in different fields.

TiO2 nanoparticles combined with polystyrene nanoplastics aggravated reproductive toxicity in female mice via exacerbating intestinal barrier disruption.

TiO2 nanoparticles (NPs), a widely used food additive in the food industry, have been shown to aggravate the progress of metabolic diseases. Nanoplastics (NPLs) are an emerging contaminant widely present in the food system and have been shown to induce ovarian disorders in mammals. Noteworthy, they can be ingested by humans through "contaminated" food, while the potential toxicity of NPLs and TiO2 NPs combined remains unclear. In this work, we investigated the potential effects and mechanisms of co-exposure to polystyrene (PS) NPLs and TiO2 NPs on the ovary in female mice. Our results revealed that the co-exposure of TiO2 NPs and PS NPLs caused significant injury to ovarian structure and function, but individual exposure had no effect. Moreover, compared to the TiO2 NPs group, co-exposure aggravated the intestinal barrier damage in mice, increasing the bioaccumulation of TiO2 NPs in the ovary. After being supplemented with the oxidative stress inhibitor N-acetyl-L-cysteine, the expression of ovarian antioxidant genes increased, and the ovarian structural and functional injury in co-exposure mice reverted to normal levels. This study demonstrated that co-exposure to PS NPLs and TiO2 NPs can cause more severe female reproductive dysfunction and deepened the toxicological insights between NPLs and NPs. This article is protected by copyright. All rights reserved.

TiO2 nanoparticles affect spermatogenesis and adhesion junctions via the ROS-mediated mTOR signalling pathway in Eriocheir sinensis testes

Recent findings found that TiO2 nanoparticles (TiO2-NPs) have male reproductive toxicity. However, few reports have studied the toxicity of TiO2-NPs in crustaceans. In this study, we first chose the freshwater crustacean Eriocheir sinensis (E. sinensis) to explore the male toxicity of TiO2-NP exposure and the underlying mechanisms. Three nm and 25 nm TiO2-NPs at a dose of 30 mg/kg bw induced apoptosis and damaged the integrity of the haemolymph-testis-barrier (HTB, a structure similar to the blood-testis-barrier) and the structure of the seminiferous tubule. The 3-nm TiO2-NPs caused more severe spermatogenesis dysfunction than the 25-nm TiO2-NPs. We initially confirmed that TiO2-NP exposure affected the expression patterns of adherens junctions (α-catenin and β-catenin) and induced tubulin disorganization in the testis of E. sinensis. TiO2-NP exposure caused reactive oxygen species (ROS) generation and an imbalance of mTORC1-mTORC2 (mTORC1/rps6/Akt levels were increased, while mTORC2 activity was not changed). After using the ROS scavenger NAC to inhibit ROS generation, both the mTORC1-mTORC2 imbalance and alterations in AJs were rescued. More importantly, the mTORC1 inhibitor rapamycin abolished mTORC1/rps6/Akt hyperactivation and partially restored the alterations in AJs and tubulin. Collectively, the mTORC1-mTORC2 imbalance induced by TiO2-NPs was involved in the mechanism of AJ and HTB disruption, resulting in spermatogenesis in E. sinensis.

Assessment of combined algal toxicity of TiO2 nanoparticles and organochlorines in karst surface waters

The widespread use of nanoparticles (NPs) and organic pollutants increases the risk of their coexistence in the aquatic environments. It is uncertain how the combined toxicities of NPs and OCs affect aquatic organisms in surface waters. In this study, the binary combined toxicities of TiO2 NPs with three different organochlorines (OCs)-pentachlorobenzene (PeCB), 3,3,4,4-tetrachlorobiphenyl (PCB-77), and atrazine on Chlorella pyrenoidosa in three karst surface water bodies were investigated. The correlation analysis results indicated that the toxicities of TiO2 NPs and OCs to algae were mainly related to the total organic carbon (TOC) and ionic strength of surface water. Surface water relieved the growth inhibition of the pollutants on algae as compared with ultrapure water (UW). The combined toxic effect caused by the co-exposure of TiO2 NPs-atrazine was synergistic and had an antagonistic effect for TiO2 NPs-PCB-77 in four types of water bodies. However, the co-exposure of TiO2 NPs-PeCB had an additive effect in the Huaxi Reservoir (HX) and synergistic effects in Baihua Lake (BH), Hongfeng Lake (HF), and UW. TiO2 NPs increased the bioaccumulation of OCs by algae. Both PeCB and atrazine significantly increased the bioaccumulation of TiO2 NPs by algae, except for PeCB in HX; however, PCB-77 reduced the bioaccumulation of TiO2 NPs by algae. The toxic effects of TiO2 NPs and OCs on algae in different water bodies were the result of the nature of the pollutants, bioaccumulation, hydrochemical properties, and other factors.

Fascinating strategies of marine benthic organisms to cope with emerging pollutant: Titanium dioxide nanoparticles

Titanium dioxide nanoparticles (NPs) have numerous applications, and their demands have increased as an alternative for banned sunscreen filters. However, the underlying mechanisms of their toxicity, remain largely unknown. Here, we investigate the mechanism of TiO2 NP cytotoxicity and detoxification through time-course experiments (1, 6, and 24 h) based on cellular observations and single-cell transcriptome analyses in a marine benthic foraminifer strain, derived from a common unicellular eukaryotic organism worldwide. After exposure for 1 h, cells enhanced the production of reactive oxygen species (ROS) in acidic endosomes containing TiO2 NPs as well as in mitochondria. In acidic endosomes, ROS were produced through the Fenton reaction on the surface of charged TiO2 NPs. In mitochondria, ROS were associated with porphyrin synthesis that chelated metal ions. Glutathione peroxide and neutral lipids acted as a sink for free radicals, whereas lipid peroxides were excreted to prevent further radical chain reactions. By 24 h, aggregated TiO2 NPs were encapsulated in organic compounds, possibly ceramide, and excreted as mucus, thereby preventing their further uptake. Thus, we reveal that foraminifers can tolerate the toxicity of TiO2 NPs and even prevent their further phagocytosis and uptake by trapping TiO2 NPs inside mucus. This previously unknown strategy could be applied in bioremediation to sequester NPs from the marine environment and can guide management of TiO2 pollution.

Nephroprotective Effect of Cinnamon cassia and Azadirachta indica on Titanium Dioxide Nanoparticles

Introduction: Titanium Dioxide (TiO2) has gained a lot of focus in today’s world owing to its wide usage in several industries. The hazardous effects of TiO2 and its nanoparticles are also slowly revealing. The need for a proper cure of these toxic effects is of utmost importance. Due to its few side effects, medicinal plants can be an efficient source of remedy but are least considered compared to synthetic medicines. Cinnamomum cassia and Azadirachta indica are the most common of such medicinal plants used extensively in Pakistan and India. In this study, we carried out experiments to know the toxic effects of TiO2 nanoparticles in kidneys using a murine model and observed the ameliorating effects of Cinnamomum cassia and Azadirachta indica on the toxicity of TIO2 nanoparticles. Methods: Rats were given a subcutaneous injection of TiO2 nanoparticles at the dose of 150mg/kg body weight for 28 days along with oral administration of Cinnamomum cassia and Azadirachta indica alone and in combination. Results and Discussion: Both Cinnamomum cassia and Azadirachta indica at doses of 100 or 150mg/kg reduced the toxic effects of TiO2 nanoparticles evident from reduced alterations in kidney histopathology and also decreased DNA damage. Conclusion: It was concluded that Cinnamomum cassia and Azadirachta indica showed remedial or healing effects against nephrotoxicity in rats exposed to TiO2 sublethal doses.

Combined toxic effects of TiO2 nanoparticles and organochlorines on Chlorella pyrenoidosa in karst area natural waters

With the discharge of nanoparticles (NPs) into the environment, NPs can interact with coexisting organic pollutants, resulting in combined toxic effects. In order to more realistically evaluate the potential toxic effects of NPs and coexisting pollutants on aquatic organisms. We evaluated the combined toxicities of TiO2 nanoparticles (TiO2 NPs) and three different organochlorines(OCs)-pentachlorobenzene (PeCB), 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) and atrazine to algae (Chlorella pyrenoidosa) in three karst natural waters. The results indicate that the individual toxicities of TiO2 NPs and OCs in natural waters were less than those of OECD medium, and the combined toxicities were different from but generally similar to those of OECD medium. The individual and combined toxicities were the largest in UW. The correlation analysis showed that the toxicities of TiO2 NPs and OCs were mainly related to TOC, ionic strength, Ca2+ and Mg2+ in natural water. The binary combined toxicities of PeCB and atrazine with TiO2 NPs to algae were synergistic. The binary combined toxicity of TiO2 NPs and PCB-77 to algae was antagonistic. The presence of TiO2 NPs increased the algae-accumulations of OCs. PeCB and atrazine all increased the algae-accumulations of TiO2 NPs, while PCB-77 showed the opposite result. The above results indicated that due to the influence of different hydrochemical properties in karst natural waters, there were differences between TiO2 NPs and OCs in their toxic effects, structural and functional damage, and bioaccumulation.

Study of the Embryonic Toxicity of TiO2 and ZrO2 Nanoparticles

Currently, the widespread use of TiO2 and ZrO2 nanoparticles (NPs) in various industries poses a risk in terms of their potential toxicity. A number of experimental studies provide evidence of the toxic effect of TiO2 and ZrO2 NPs on biological objects. In order to supplement the level of knowledge and assess the risks of toxicity and danger of TiO2 and ZrO2 NPs, we decided to conduct a comprehensive experiment to study the embryonic toxicity of TiO2 and ZrO2 NPs in pregnant rats. For the experiment, mongrel white rats during pregnancy received aqueous dispersions of powders of TiO2 and ZrO2 NPs at a dose of 100 mg/kg/day. To characterize the effect of TiO2 and ZrO2 NPs on females and the postnatal ontogenesis of offspring, a complex of physiological and biochemical research methods was used. The results of the experiment showed that TiO2 NPs as ZrO2 NPs (100 mg/kg per os) cause few shifts of similar orientation in the maternal body. Neither TiO2 NPs nor ZrO2 NPs have an embryonic and teratogenic effect on the offspring in utero, but both modify its postnatal development.

Investigation of toxicity of TiO2 nanoparticles on glioblastoma and neuroblastoma as the most widely used nanoparticles in photocatalytic processes

Background: Titanium dioxide (TiO2 ) nanoparticles (NPs) are among the most important and usable photocatalysts. Recently, the biological properties of these NPs, particularly, its anticancer activity, have been considered. Glioblastoma and neuroblastoma are two fatal brain tumors with a high mortality rate in humans, the hope for treatment of which is weak by the common methods. Methods: In this study, the cytotoxicity effects of TiO2 alone and in combination with ultraviolet A (UVA) irradiation on two different cell lines, neuroblastoma (SH-SY5Y) and glioblastoma U87, were investigated. After administration of 10, 50, 100, and 500 μg/mL TiO2 , 0.043 and 1.4 mW/cm2 UVA irradiation, cell viability was investigated after 4, 24, and 48 hours by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Results: MTT assay and light microscope demonstrated that the effect of TiO2 NPs varied based on the dose of the substance, the impact time, the cell type, and the amount of radiation. In this study, for NPs alone, both toxicity and non-toxicity of the substance were observed. For NPs in the presence of UV, based on the comparison with its status alone and the difference in the viability assay of the two groups, both the photocatalytic and the coating effect of the NPs were observed. Conclusion: According to the results, different concentrations of TiO2 can be used for different purposes. Low concentrations of TiO2 can be used to increase the efficiency of photodynamic therapy and high concentrations of TiO2 can be used to protect the normal cell. This strategy improves the photodynamic therapy and reduces the harmful effects.

UV-dependent freshwater effect factor of nanoscale titanium dioxide for future life cycle assessment application.

Environmental impacts of nanoscale titanium dioxide (TiO2 ) should be assessed throughout the lifetime of nanoparticles (NPs) to improve the state of knowledge of the overall sustainability. Life cycle assessment (LCA) has been previously recognized as a promising approach to systematically evaluating environmental impacts of NPs. As a result of their unique nanospecific properties, characterization factors (CF) were previously used for compensating the release and potential impacts of TiO2 NPs. However, because TiO2 NPs are known to generate reactive oxygen species and elicit toxicity to freshwater organisms, the lack of adequate UV-dependent effect factors (EFs) remains a major shortcoming when addressing their life cycle impacts. To complement the LCA of TiO2 -NPs-enabled products under their specific applications, we recapitulated the freshwater toxicity of TiO2 NPs and then modeled in USEtox to determine trophic level EF ranges under UV and non-UV exposure conditions. Results indicate that EFs derived for non-UV exposure were 52 (42.9-65) potentially affected fraction (PAF) m3 /kg, and combined toxicity data derived EFs were 70.1 (55.6-90.5) PAF m3 /kg. When considering only the UV-induced exposure condition, the modeled EF increased to 500 (333-712) PAF m3 /kg. Our work highlights that case-dependent EFs should be considered and applied to reflect more realistic ecological impacts and illustrate comprehensive life cycle environmental impacts for nanoenabled products. Integr Environ Assess Manag 2023;19:578-585. © 2022 SETAC.

Effect of real food matrix on the behavior and toxicity of TiO2 nanoparticles

Effect of real food matrix on the behavior and toxicity of TiO2 nanoparticles

Effects and Mechanism of Two Nanoparticles (Titanium Dioxide and Silver) to Moina mongolica Daday (Crustacea, Cladocera)

The nearshore and estuary are the main gathering areas of nanoparticles (NPs), and salinity change is a crucial characteristic in these marine areas. Moina mongolica Daday is an important open-ended bait in the nearshore aquaculture environment. Investigating the toxicity mechanism of NPs to M. mongolica under different salinity conditions is crucial to exploring the biological impact of NPs in the nearshore environment. Two typical metal oxide and metal NPs of TiO2 and Ag were used in this study to test the acute, chronic, and reproductive toxicities of M. mongolica (Cladocera) in marine environments of different salinity gradients. The toxic effects and mechanisms of the two NPs on M. mongolica were discussed by ecotoxicology and transcriptional analysis, respectively. A total of 27,274 genes were assembled, and 11,056 genes were successfully compared. Results suggested that TiO2 and Ag NPs showed particle toxicity with oxidation generation and immune emergencies on M. mongolica. Compared with TiO2, Ag NPs showed strong toxicity with reproductive toxicity due to the release of Ag+, resulting in a reduction in reproduction, which is a decrease in the number of offspring and the rm. Critical DEGs involved in carapace showed carapace damage of M. mongolica, due to adhesion and accumulation (approximately 40%–60% of all accumulation) on carapace, which was one of the toxic mechanisms of the two NPs. The salinity factor caused the aggregation of both NPs, and Ag+ release of Ag NPs. The toxicity of TiO2 NPs to M. mongolica increases with salinity, but that of Ag NPs decreases.

In vivo intrinsic atomic interaction infer molecular eco-toxicity of industrial TiO2 nanoparticles via oxidative stress channelized steatosis and apoptosis in Paramecium caudatum

The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of − 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.

Harnessing rat derived model cells to assess the toxicity of TiO2 nanoparticles

Until now, a few studies have been conducted on the destructive effects of TiO2 NPs in living organisms, and studies on the toxicity of TiO2 NPs are still in the beginning phases. Because of the widespread use of TiO2 NPs in all areas of human life, it is essential to study their profound and fundamental toxic effects on each organ and body cell. Herein, we evaluate the effect of exposure to TiO2 NPs on in vitro models derived from the rat bone marrow and adipose tissues. Exposure to TiO2 NPs at 100 and 200 μg/ml exhibited cytotoxicity for the rat bone marrow mesenchymal stem cells (rBMSCs) and rat adipose mesenchymal stem cells (rATSC), respectively. Additionally, reduced rBMSCs and rATSCs frequencies in the S phase of the cell cycle. Moreover, TiO2 NPs enhanced the activity of cellular senescence-associated β-galactosidase in both model cells. Significantly higher relative expression of aging-related genes P53 and NF-kB (p < 0.05) and lower expression levels of anti-aging-related genes Nanog and SIRT1 were found in the treated cells (p < 0.05). Colony-forming and DAPI staining showed the reduction of cell growth and DNA damage in both rBMSCs and rATSCs. Our findings along with other similar findings showed that TiO2 NPs probably have negative effects on the cell growth, prompt the cells for entry into proliferation stop, DNA damage, and trigger the aging process.Graphical abstract

Nano-bio interfacial interactions determined the contact toxicity of nTiO2 to nematodes in various soils

The biological effect of soilborne nanoparticles (NPs) is a manifestation of soil-NMs-bio interactions. Soil factors are known to restructure NPs surfaces and thus influence the nanotoxicity. However, the mechanisms by which environmental factors affecting nano-bio interactions to aggravate or alleviate nanotoxicities are poorly understood. Herein, we compared the toxicity of TiO2 NPs (nTiO2) in five soils using the model nematode (Caenorhabditis elegans), and investigated the variation of nano-bio interactions under different conditions. A correlation analysis showed that pH and dissolved organic matter (DOM) were dominant regulators of nTiO2 toxicity. At the nano-bio interface, low pH (5.0) led to nTiO2 adhesion to micron-sized furrows and aggravated dermal wrinkling, while humid acid (HA) alleviated these impacts. Mechanically, low pH increased nTiO2 adhesion through enhanced electrostatic attraction and subsequent stimulation of mucin and collagen synthesis, resulting in a positive feed cycle of pH-dependent contact nanotoxicity. HA not only prevented nTiO2 adhesion onto the epidermis due to its negative charge, but also relieved the overstimulation of stress response pathways, thereby alleviating nanotoxicity. These findings broaden our knowledge of how NPs induce contact toxicity in soil invertebrates through specific biointerfacial interactions, and highlight the important role of DOM in alleviating the combined hazards of NPs and soil acidification.

Effect of titanium dioxide nanoparticles on histone modifications and histone modifying enzymes expression in human cell lines

Titanium dioxide (TiO2) nanoparticles are widely manufactured, with a range of applications in consumer products. Significant toxicity of TiO2 nanoparticles has, however, been recognized, suggesting considerable risk to human health. To evaluate fully their toxicity, assessment of the epigenetic action of these nanoparticles is critical. However, only few studies are available examining the capability of nanoparticles to alter epigenetic integrity. In the present study, the effect of TiO2 nanoparticles exposure on histone modifications, a major epigenetic mechanism, was investigated in human colorectal (Caco-2) and lung (NL20) epithelial cell lines. Histone H3 and H4 modifications were assessed by array analysis using the EpiQuickTM Histone H3 or H4 Modification Multiplex Assay. Seventeen histone modifications were identified with altered levels after exposure to TiO2 nanoparticles. Changes in several selected histone modifications (Caco-2 cells: H3cit, H3K9me3, H3K27me3, H3K36me3, H3K9ac, and H4K8ac; NL20 cells: H3K4me3, H3K9me3, H3K27me3, H3K9ac, and H3K18ac) were verified by Western blot analysis. The results also revealed aberrant expression of histone modifying enzymes in TiO2 exposed cells. Expression levels were determined by array analysis using the Human Epigenetic Chromatin Modification Enzymes RT2 Profiler™ PCR Array, with 12 genes identified in both Caco-2 cells and NL20 cells. qRT-PCR analysis confirmed the array results for several selected histone modifying enzyme genes (ASH1L, CARM1, EHMT2, HAT1, HDAC9, KMT2E, NCOA1, SETDB2, and USP16). The findings from this study clearly demonstrate the impact of TiO2 nanoparticles exposure on histone modification in two human cell lines, supporting potential involvement of this epigenetic mechanism in the toxicity of TiO2 nanoparticles. Hence, for complete assessment of potential risk from nanoparticle exposure, epigenetic studies are critical.

Titanium dioxide nanoparticles as a risk factor for the health of Neotropical tadpoles: a case study of Dendropsophus minutus (Anura: Hylidae)

The production and use of titanium dioxide (TiO2) nanoparticles are increasing worldwide. The release of this substance into the environment can induce toxic effects in aquatic invertebrates and vertebrates, although the exact nature of its impacts on Neotropical amphibians is still poorly understood. In this context, the present study evaluated the toxicity of TiO2 nanoparticles and their counterpart-dissolved titanium dioxide (TiO2)-in the tadpoles of Dendropsophus minutus. The biometric parameters, DNA damage, and behavioral changes were verified in tadpoles exposed to three different concentrations (0.1mg·L-1, 1.0mg·L-1, and 10mg·L-1) of TiO2 nanoparticles and dissolved TiO2 for 7days. We verified significant DNA damage in the D. minutus tadpoles exposed to both forms of Ti, in comparison with the control group. We also identified a reduction in total size, body length, and width, and the height of the musculature of the tail of the tadpoles exposed to all concentrations of both substances in comparison with the control. In the behavioral test, the tadpoles exposed to nanoparticles and dissolved TiO2 presented reduced mobility and a tendency to be less aggregated than normal. Here, the simultaneous use of multiple biomarkers was fundamental for the reliable assessment of the adverse effects of nanomaterials on anuran amphibians and the establishment of a systematic approach to the biomonitoring of aquatic ecosystems. The present study expands our understanding of the genotoxic, morphological, and behavioral effects of TiO2 nanoparticles and dissolved TiO2 on anuran amphibians, and contributes to the establishment of further research for the more systematic assessment of the environmental risk of nanomaterials.

UV-B radiation enhances the toxicity of TiO2 nanoparticles to the marine microalga Chlorella pyrenoidosa by disrupting the protection function of extracellular polymeric substances

Weakened EPS protection of algal cells contributing to the increased internalization of TiO2 nanoparticles was identified as the key mechanism for the enhanced toxicity of TiO2 nanoparticles under UV-B irradiation.