TiO2 NPs Exposure Research Articles

Effects of Titanium Dioxide Nanoparticles on Cell Growth and Migration of A549 Cells under Simulated Microgravity

With the increasing application of nanomaterials in aerospace technology, the long-term space exposure to nanomaterials especially in the space full of radiation coupled with microgravity condition has aroused great health concerns of the astronauts. However, few studies have been conducted to assess these effects, which are crucial for seeking the possible intervention strategy. Herein, using a random positioning machine (RPM) to simulate microgravity, we investigated the behaviors of cells under simulated microgravity and also evaluated the possible toxicity of titanium dioxide nanoparticles (TiO2 NPs), a multifunctional nanomaterial with potential application in aerospace. Pulmonary epithelial cells A549 were exposed to normal gravity (1 g) and simulated gravity (~10−3 g), respectively. The results showed that simulated microgravity had no significant effect on the viability of A549 cells as compared with normal gravity within 48 h. The effects of TiO2 NPs exposure on cell viability and apoptosis were marginal with only a slightly decrease in cell viability and a subtle increase in apoptosis rate observed at a high concentration of TiO2 NPs (100 μg/mL). However, it was observed that the exposure to simulated microgravity could obviously reduce A549 cell migration compared with normal gravity. The disruption of F-actin network and the deactivation of FAK (Tyr397) might be responsible for the impaired mobility of simulated microgravity-exposed A549 cells. TiO2 NPs exposure inhibited cell migration under two different gravity conditions, but to different degrees, with a milder inhibition under simulated microgravity. Meanwhile, it was found that A549 cells internalized more TiO2 NPs under normal gravity than simulated microgravity, which may account for the lower cytotoxicity and the lighter inhibition of cell migration induced by the same exposure concentration of TiO2 NPs under simulated microgravity at least partially. Our study has provided some tentative information on the effects of TiO2 NPs exposure on cell behaviors under simulated microgravity.

Impacts of nano-titanium dioxide toward Vallisneria natans and epiphytic microbes

In this study, Vallisneria natans plants were exposed to 5 and 20 nm of titanium dioxide nanoparticles (TiO₂ NPs) anatase and 600–1000 nm of bulk at 5 and 20 mg/L for 30 days. SEM images and EDX spectra revealed that epiphytic biofilms were more prone to TiO₂ NPs adhesion than bare plant leaves. TiO₂ NPs injured plant leaf cells, ruptured epiphytic diatoms membranes and increased the ratio of free-living microbes. The TN, NH4⁺-N and NO3ˉ-N concentrations significantly decreased, respectively, by 44.9%, 33.6%, and 23.6% compared to bulk treatments after 30 days due to macrophyte damage and a decline in diversity of epiphytic bacterial community and abundance of nitrogen cycle bacteria. TiO₂ NPs size-dependent decrease in bacterial relative abundance was detected, including phylum Cyanobacteria, Planctomycetes, and Verrucomicrobia. Although TiO₂ NPs increased eukaryotic diversity and abundance, abundances of Bacillariophyceae and Vampyrellidae classes and Gastrotricha and Phragmoplastophyta phylum decreased significantly under TiO₂ NPs exposure compared to bulk and control. TiO₂ NPs reduced intensities of interaction relationships among epiphytic microbial genera. This study shed new light on the potential effects of TiO₂ NPs toxicity toward aquatic plants and epiphytic microbial communities and its impacts on nitrogen species removal in wetlands.

Single-cell transcriptomics uncovers the impacts of titanium dioxide nanoparticles on human bone marrow stromal cells

Titanium dioxide nanoparticles (TiO2 NPs) have attracted substantial attention in various applications, including environmental remediation and nanomedicine. A detailed understanding of the toxicity of TiO2 NPs and the underlying mechanisms is fundamental to further development of their environmental and biomedical applications. Herein, we determined the changes in the transcriptional profile of human bone marrow stromal cells (BMSCs) after a set of different sized TiO2 NPs exposure using single-cell RNA-seq (scRNA-seq). By taking advantage of sensitivity of scRNA-seq, we found that TiO2 NPs exposure led to profound changes in gene expression and DNA damage signaling played a pivotal role in cellular responses to TiO2 NPs exposure. Smaller TiO2 NPs (5, 14 nm) led to a response similar to antivirus defense, and bigger TiO2 NPs (54, 135, and 228 nm) induced proliferation and differentiation changes in transcriptional levels. Validation experiments on representative genes showed that some genes might be served as biomarkers of TiO2 NPs exposure. Furthermore, in vitro and in vivo analyses showed remarkable over-production of reactive oxygen species (ROS) but did not affect osteogenic differentiation potential in BMSCs. The results unveiled landscape changes in transcriptomes in BMSCs induced by TiO2 NPs, which provides new insights into toxicity assessments of nanomaterials.

Effects of Titanium Dioxide Nanoparticles on Porcine Prepubertal Sertoli Cells: An "In Vitro" Study.

The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. Titanium dioxide nanoparticles (TiO2 NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO2 NPs induced reproductive toxicity in male animals. In this in vitro study, porcine prepubertal Sertoli cells (SCs) have undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposures at both subtoxic (5 µg/ml) and toxic (100 µg/ml) doses of TiO2 NPs. After performing synthesis and characterization of nanoparticles, we focused on SCs morphological/ultrastructural analysis, apoptosis, and functionality (AMH, inhibin B), ROS production and oxidative DNA damage, gene expression of antioxidant enzymes, proinflammatory/immunomodulatory cytokines, and MAPK kinase signaling pathway. We found that 5 µg/ml TiO2 NPs did not induce substantial morphological changes overtime, but ultrastructural alterations appeared at the third week. Conversely, SCs exposed to 100 µg/ml TiO2 NPs throughout the whole experiment showed morphological and ultrastructural modifications. TiO2 NPs exposure, at each concentration, induced the activation of caspase-3 at the first and second week. AMH and inhibin B gene expression significantly decreased up to the third week at both concentrations of nanoparticles. The toxic dose of TiO2 NPs induced a marked increase of intracellular ROS and DNA damage at all exposure times. At both concentrations, the increased gene expression of antioxidant enzymes such as SOD and HO-1 was observed whereas, at the toxic dose, a clear proinflammatory stress was evaluated along with the steady increase in the gene expression of IL-1α and IL-6. At both concentrations, an increased phosphorylation ratio of p-ERK1/2 was observed up to the second week followed by the increased phosphorylation ratio of p-NF-kB in the chronic exposure. Although in vitro, this pilot study highlights the adverse effects even of subtoxic dose of TiO2 NPs on porcine prepubertal SCs functionality and viability and, more importantly, set the basis for further in vivo studies, especially in chronic exposure at subtoxic dose of TiO2 NPs, a condition closer to the human exposure to this nanoagent.

Retinal cytotoxicity of silica and titanium dioxide nanoparticles.

The retina plays a key role in human vision. It is composed of cells that are essential for vision signal generation. Thus far, conventional medications have been ineffective for treating retinal diseases because of the intrinsic blood-retinal barrier. Nanoparticles (NPs) are promising effective platforms for ocular drug delivery. However, nanotoxicity in the retinal tissue has not received much attention. This study used R28 cells (a retinal precursor cell line that originated from rats) to investigate the safety of two commonly used types of NPs: silica nanoparticles (SiO2NPs, 100nm) and titanium dioxide nanoparticles (TiO2NPs, 100nm). Cellular viability and reactive oxygen species generation were measured after 24, 48, and 72h of exposure to each NP. Cellular autophagy and the mTOR pathways were evaluated. The retinal toxicity of the NPs was investigated in vivo in rat models. Both types of NPs were found to induce significant dose-dependent toxicity on the R28 cells. A significant elevation of reactive oxygen species generation was also observed. Increased autophagy and decreased mTOR phosphorylation were observed after SiO2NPs and TiO2NPs exposure. The diffuse apoptosis of the retinal cellular layers was detected after intravitreal injection.

MicroRNAs as a Suitable Biomarker to Detect the Effects of Long-Term Exposures to Nanomaterials. Studies on TiO2NP and MWCNT.

The presence of nanomaterials (NMs) in the environment may represent a serious risk to human health, especially in a scenario of chronic exposure. To evaluate the potential relationship between NM-induced epigenetic alterations and carcinogenesis, the present study analyzed a panel of 33 miRNAs related to the cell transformation process in BEAS-2B cells transformed by TiO2NP and long-term MWCNT exposure. Our battery revealed a large impact on miRNA expression profiling in cells exposed to both NMs. From this analysis, a small set of five miRNAs (miR-23a, miR-25, miR-96, miR-210, and miR-502) were identified as informative biomarkers of the transforming effects induced by NM exposures. The usefulness of this reduced miRNA battery was further validated in other previously generated transformed cell systems by long-term exposure to other NMs (CoNP, ZnONP, MSiNP, and CeO2NP). Interestingly, the five selected miRNAs were consistently overexpressed in all cell lines and NMs tested. These results confirm the suitability of the proposed set of mRNAs to identify the potential transforming ability of NMs. Particular attention should be paid to the epigenome and especially to miRNAs for hazard assessment of NMs, as wells as for the study of the underlying mechanisms of action.

Mixture toxicity of TiO2 NPs and tetracycline at two trophic levels in the marine ecosystem: Chlorella sp. and Artemia salina

Increasing usage of both nanomaterials and pharmaceuticals and their unabated release to the marine ecosystem pose a serious concern nowadays. The toxicity of the mixture of TiO2 NPs and tetracycline (TC) in the marine species are not very well covered in prior literature. The current study explores the joint toxic effects of TiO2 NPs and TC in a simulated marine food chain: Chlorella sp. and Artemia salina. Chlorella sp. was interacted with pristine TiO2 NPs (0.05, 05, and 5 mg/L), TC (0.5 mg/L), and their combinations for 48 h. The toxicity induced in Chlorella sp. by pristine TiO2 NPs through oxidative stress and chloroplast damage was not significantly changed in the presence of TC. Principal component analysis for the toxicity parameters revealed a strong association between growth inhibition and adsorption/internalization. In the second trophic level (A. salina), the waterborne exposure of TC additively increased the toxicity of TiO2 NPs. Both adsorption and degradation played a major role in the removal of TC from the suspension, resulting in additive toxic effects in both Chlorella sp. and A. salina. Compared to the waterborne exposure, the foodborne exposure of TiO2 NPs and TC induced lesser toxic effects owing to reduced uptake and accumulation in A. salina. Biomagnification results indicate that the dietary transfer of TiO2 NPs and TC does not pose a serious environmental threat in this two-level marine food chain.

Developmental titanium dioxide nanoparticle exposure induces oxidative stress and neurobehavioral changes in zebrafish.

The widespread commercial application of titanium dioxide nanoparticles (TiO2 NPs) leads to ubiquitous presence of TiO2 NPs in the aquatic environment, which highlights the necessity to determine their potential adverse effects on aquatic organisms. The developing nerve system is particularly susceptible to environment perturbation. However, few studies have explored the developmental neurobehavioral toxicity of TiO2 NPs, especially at smaller particle size ranges (≤20nm) that have relatively longer retention time in the water column. In this study, zebrafish embryos were exposed to non-teratogenic concentrations of 0.1 and 1mg/L TiO2 NPs (average size of 14-20nm) from 8 to 108h post-fertilization (hpf) followed by various assessments at different time points up to 12 days post-fertilization (dpf). Our findings revealed that 1mg/L TiO2 NPs perturbed the motor and social behaviors in larval zebrafish. These behavioral changes were characterized by decreased swimming speed in a locomotor response test at 5dpf, increased travel distance in a flash stimulus test at 5dpf, increased preference to the light zone in a light/dark preference test at 10dpf, and increased mirror attack and percent time spent in the mirror zone in a mirror stimulus response assay at 12dpf. Mechanistic examinations at 5dpf revealed elevated cell apoptosis and oxidative stress. Cell apoptosis was characterized by increased acridine orange (AO) positive cells in the olfactory region and neuromasts of the lateral line system. Oxidative stress was characterized by increased lipid peroxidation, increased ROS production, and upregulated catalase (cat) gene expression. In addition, TiO2 NP exposure also upregulated genes associated with the developmental nervous system such as the growth associated protein 43 (gap43) and proliferating cell nuclear antigen (pcna). Our results suggest that the neurobehavioral changes in larvae exposed to 1mg/L TiO2 NPs during early development may result from cell apoptosis and oxidative stress induced neuronal damages.

Effects of Prenatal Exposure to Titanium Dioxide Nanoparticles on DNA Methylation and Gene Expression Profile in the Mouse Brain.

Background and Objectives: Titanium dioxide nanoparticles (TiO2-NP) are important materials used in commercial practice. Reportedly, TiO2-NP exposure during pregnancy can affect the development of the central nervous system in mouse offspring; however, the underlying mechanism remains unknown. In the present study, we investigated the impact of prenatal TiO2-NP exposure on global DNA methylation and mRNA expression patterns in the brains of neonatal mice. Materials and Methods: Pregnant C57BL/6J mice were intratracheally administered a TiO2-NP suspension (100 μg/mouse) on gestational day 10.5, and brains were collected from male and female offspring at day 1 postpartum. After extraction of methylated DNA by immunoprecipitation, the DNA methylation profile was analyzed using a mouse CpG island microarray. Total RNA was obtained, and mRNA expression profiles were comprehensively assessed using microarray analysis. Results: Among genes in the CpG island microarray, DNA methylation was increased in 614 and 2,924 genes and decreased in 6,220 and 6,477 genes in male and female offspring, respectively. Combined with mRNA microarray analysis, 88 and 89 genes were upregulated (≥1.5-fold) accompanied by demethylation of CpG islands, whereas 13 and 33 genes were downregulated (≤0.67-fold) accompanied by methylation of CpG islands in male and female offspring mice, respectively. Gene Set Enrichment Analysis (GSEA) revealed that these genes were enriched in gene ontology terms related to the regulation of transcription factors, cell proliferation, and organism development. Additionally, MeSH terms related to stem cells and morphogenesis were enriched. Conclusion: Prenatal TiO2-NP exposure induced genome-wide alterations in DNA methylation and mRNA expression in the brains of male and female offspring. Based on GSEA findings, it can be speculated that prenatal TiO2-NP exposure causes adverse effects on brain functions by altering the DNA methylation state of the fetal brain, especially neural stem cells, resulting in the subsequent abnormal regulation of transcription factors that modulate development and differentiation.

Inductive effect of titanium dioxide nanoparticles on the anticancer compounds production and expression of rosmarinic acid biosynthesis genes in Dracocephalum kotschyi transformed roots

Methoxylated flavonoids, mainly xanthomicrol and cirsimaritin that can be extracted from Dracocephalum kotschyi Boiss, have anticancer, antispasmodic and antiplatelet effects. The production of these valuable pharmaceutical compounds is one of the major goals of biotechnology studies. In this work, induced transformed roots were influenced by various concentrations of titanium dioxide nanoparticles (TiO2 NPs) at 24 or 48 h exposure time. The effects of TiO2 NPs were assessed on growth rate, activity of antioxidant enzymes, total phenol and flavonoid content (TPC and TFC) and rosmarinic acid (RA) and some flavonoids accumulation. The gene expression level of phenylalanine ammonia-lyase (pal) and rosmarinic acid synthase (ras) genes were assessed by real time PCR analysis. The transformed roots biomass was substantially increased in elicited roots in comparison with the control. The TPC, TFC and antioxidant enzymes activitywere affected by TiO2 NPs concentration and exposure time. Valuable flavonoids with anticancer characteristics along with xanthomicrol, cirsimaritin and isokaempferide exhibited an increase (70, 34.28 and 7.81-fold, respectively) versus the control. The maximum content of RA (530.5 μg g−1 FW), which was 4.30 times as great as that of control was detected in samples treated with TiO2 NPs (50 mg L−1) 24 h after elicitation. Real-time PCR analysis revealed a considerable increase in pal and ras expression rate engaged by TiO2 NPs levels and exposure time. Overall D. kotschyi transformed roots elicitation by TiO2 NPs led to a massive increment in the production of valuable anticancer flavonoids such as xanthomicrol, cirsimaritin and RA as polyphenol.

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma.

Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity.

Lycopene Alleviates Titanium Dioxide Nanoparticle-Induced Testicular Toxicity by Inhibiting Oxidative Stress and Apoptosis in Mice.

The research was carried out to investigate the possible ameliorative effect of lycopene on TiO2 NPs-induced male reproductive toxicity and explore the possible mechanism. Ninety-six healthy male Institute of Cancer Research (ICR) mice were equally divided into eight groups (control group, 50mg/kg TiO2 NPs group, 5mg/kg LYC group, 20mg/kg LYC group, 40mg/kg LYC group, 50mg/kg TiO2 NPs + 5mg/kg LYC group, 50mg/kg TiO2 NPs + 20mg/kg LYC group, 50mg/kg TiO2 NPs + 40mg/kg LYC group), and the mice were treated by intragastric administration every day for 30days in this research. Sperm parameters, testicular histopathology, oxidant and antioxidant enzymes, and cell apoptosis-related protein expression in the testicular tissue were analyzed. The results showed that TiO2 NPs exposure significantly decreased sperm count and motility, and TiO2 NPs also increased sperm malformation in the epididymis; these characteristics were improved when co-administration with LYC. Testicular histopathological lesions like disorder of germ cells arrange, detachment, atrophy, and vacuolization were observed after TiO2 NPs exposure, and these abnormalities were effectively ameliorated by co-administration with LYC. Oxidative stress was induced by TiO2 NPs exposure as evidenced by increased the level of MDA and decreased the activity of SOD as well as the level of anti-O2-, and these alterations were effectively prevented by co-administration with LYC. LYC also alleviated TiO2 NPs-induced germ cell apoptosis by inhibiting mitochondrial apoptotic pathway, as shown by the upregulation of Bcl-2, the downregulation of Bax, Cleaved Caspase 3, and Cleaved Caspase 9. LYC could ameliorate TiO2 NPs-induced testicular damage via inhibiting oxidative stress and apoptosis, which could be used to alleviate the testicular toxicity associated with TiO2 NPs intake.

Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring

BackgroundPregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited.MethodsIn the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring.ResultsThe results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis.ConclusionsThis is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women.Graphical abstract

Damaging effects of TiO2 nanoparticles on the ovarian cells of Bombyx mori.

As a new type of biologically compatible material, TiO2 NPs are widely used in the industry as additives, drug carriers, and components of skin care products. Due to their wide use, residual TiO2 NPs in the environment are a safety concern that has attracted extensive attention. In this study, the ovarian cell line BmN of the model organism Bombyx mori was used to reveal the damaging effects of TiO2 NPs exposure. The results demonstrated that TiO2 NPs exhibited a dose-dependent effect on the relative cell viability, with significant toxic effects being observed above 20mg/L. Oxidative damage analysis showed that ROS accumulated significantly in BmN cells after exposure to TiO2 NPs (P ≤ 0.05) and induced DNA damage. Further analysis revealed that the transcriptional levels of key superoxide dismutase genes (SOD) decreased significantly, while the transcriptions of key genes of the MAPK/NF-κB signaling pathway (P38, MEK, ERK and REL) and the downstream inflammatory factor genes (IL6 and TNFSF5) were all significantly up-regulated (P ≤ 0.05). Overall, our results indicate that exposure to TiO2 NPs leads to reduced transcription of antioxidant genes, accumulation of peroxides, and inflammation. These findings provide valuable data for the safety evaluation of environmental residues of TiO2 NPs.

Metabolomics screening of serum biomarkers for occupational exposure of titanium dioxide nanoparticles

Although nanotoxicology studies have shown that respiratory exposure of titanium dioxide nanoparticles (TiO2 NPs) could induce adverse health effects, limited biomarkers associated with occupational exposure of TiO2 NPs were reported. The purpose of this study is to screen serum biomarkers among workers occupationally exposed to TiO2 NPs using metabolomics. Compared with the control group, a total of 296 serum metabolites were differentially expressed in the TiO2 NPs-exposed group, of which the relative expression of 265 metabolites increased, and the remaining 31 decreased. Three machine learning methods including random forest (RF), support vector machines (SVM), and boruta screened eight potential biomarkers and simultaneously selected a metabolite, Liquoric acid. Through multiple linear regression analysis to adjust the influence of confounding factors such as gender, age, BMI, smoking and drinking, occupational exposure to TiO2 NPs was significantly related to the relative expression of the eight potential biomarkers. Meanwhile, the receiver operating characteristic curves (ROCs) of these potential biomarkers had good sensitivity and specificity. These potential biomarkers were related to lipid peroxidation, and had biological basis for occupational exposure to TiO2 NPs. Therefore, it was demonstrated that the serum metabolites represented by Liquoric acid were good biomarkers of occupational exposure to TiO2 NPs.

Titanium dioxide nanoparticles alter reproductive and thyroid hormones of Labeo rohita females: Amelioration through vitamin E and folic acid

The present study aimed to understand titanium dioxide nanoparticle (TiO2-NPs) induced changes in selected hormones of hypothalamic-pituitary-thyroid/gonad axis in adult females of Labeo rohita, as well as the possible ameliorative role of dietary vitamin E and folic acid. Firstly, adult females of Labeo rohita were injected intraperitoneally with two sublethal doses (1/50 LD50; 10.6 μg kg−1 and 1/10 LD50; 52.8 μg kg−1) of TiO2-NPs and the effect in terms of gonadosomatic index, reproductive & thyroid hormones, vitellogenin, and cortisol were assessed after 21 days of exposure. Subsequently, TiO2-NPs pre-exposed fish were supplemented with vitamin E and folic acid in different combinations for 30 days. The control diet fulfilled the minimum requirement, while two higher doses of vitamin E (200 and 250 mg/kg diet) and folic acid (3 and 4 mg/kg diet) were used in experimental diets. The results showed significant alteration of gonadotropins (an increase of FSH and LH), thyroid hormones (an increase of T3 and T4 without substantial change in TSH), cortisol, steroid hormones, and vitellogenin, upon TiO2-NPs exposure. Among the steroid hormones, testosterone and progesterone levels declined significantly with a concomitant increase in estradiol. More precisely, exposure to 52.8 μg kg−1 TiO2-NPs increased serum estradiol and cortisol to the extent of 98% and 77%, respectively. While serum vitellogenin in Labeo rohita exposed to low and high doses of TiO2-NPs decreased by 29% and 58%, respectively, indicating the adverse effect of TiO2-NPs on reproduction. Dietary administration of vitamin E and folic acid reduced oxidative stress as characterized by lowered antioxidative enzyme's activities. Further, most of the harmful effects of TiO2-NPs were ameliorated by dietary fortification of vitamin E and folic acid, with vitamin E having more pronounced effect.

Nono-titanium dioxide exposure during the adolescent period induces neurotoxicities in rats: Ameliorative potential of bergamot essential oil.

IntroductionIn adolescence, the brain is still maturing, and disorders in maturation may affect the normal development of the brain. Exposure to titanium dioxide nanoparticles (TiO2 NPs) has various potential negative effects on the central nervous system. Bergamot essential oil (BEO) has been found to be effective for neuroprotection.MethodsThe rats were injected intraperitoneally with TiO2 NPs (20 mg/kg) and/or BEO (200 mg/kg). The endogenous antioxidant state and inflammatory parameters were estimated using ELISA kits, and then the memory ability and anxiety‐like behavior in rats were assessed.ResultsTiO2 NPs exposure during the adolescent period induced anxiety‐like behavior, cognitive impairment, neuroinflammation and oxidative damage in hippocampus, and BEO treatment could significantly ameliorate the neurotoxicities induced by TiO2 NPs exposure.ConclusionOur results suggest that the negative effects of TiO2 NPs exposure during the adolescent period on anxiety‐like behavior and cognitive function may be related to oxidative stress and neuroinflammation induced by TiO2 NPs exposure. In addition, BEO may ameliorate the neurotoxicities induced by TiO2 NPs exposure in adolescent rats through the antioxidant and anti‐inflammatory activity of BEO.

Compositional and functional responses of bacterial community to titanium dioxide nanoparticles varied with soil heterogeneity and exposure duration

Titanium dioxide nanoparticles (TiO2 NPs) are widely used as nano-agrochemicals. In this study we investigated the influence of soil heterogeneity on bacterial communities exposed to TiO2 NPs over time. Clay and sandy soils with low- and high-organic matter contents were exposed to environmentally relevant concentration of TiO2 NPs (1 mg/kg) and soil bacterial communities were sampled after short-term (15 days) and long-term exposure (60 days). After short-term TiO2 NPs exposure, significant effects regarding the enzyme activity, bacterial community structure and composition, and community functioning were observed in the clay soils with high organic matter (clay-HOM) but not in other soil groups. Response alterations were observed to taxa belonging to Acidobacteria and Verrucomicrobia, and functional pathways related to carbohydrates degradation. These results indicated that soil heterogeneity play more important roles in shaping the bacterial community in soil with low clay fraction and less organic matter, while TiO2 NPs selection was the main driver in inducing the compositional and functional impacts on the soil bacterial community in the presence of clay soil with high organic matter content. As exposure time increased, the bacterial community recovered after a long-term exposure of 60 days, suggesting that the bacterial evolution and adaptation could overcome the TiO2 NPs selection after long-term exposure. Our results highlighted the importance of soil heterogeneity including clay fraction and organic matter and exposure duration in assessing the impact of nanoparticle on soil bacterial activity, community and function. By comprehensively evaluating the risks of nanoparticles on soil ecosystem and explicitly and explicitly include spatial and temporal variations, the benefit of nano-agrochemical products has the potential to be promoted in future applications.

Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation

BackgroundDepending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions.ResultsTiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes.ConclusionsOverall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Biochar-mediated transformation of titanium dioxide nanoparticles concerning TiO2NPs-biochar interactions, plant traits and tissue accumulation to cell translocation.

Titanium dioxide nanoparticles (TiO2NPs) application in variety of commercial products would likely release these NPs into the environment. The interaction of TiO2NPs with terrestrial plants upon uptake can disturb plants functional traits and can also transfer to the food chain members. In this study, we investigated the impact of TiO2NPs on wheat (Triticum aestivum L.) plants functional traits, primary macronutrients assimilation, and change in the profile of bio-macromolecule. Moreover, the mechanism of biochar-TiO2NPs interaction, immobilization, and tissue accumulation to cell translocation of NPs in plants was also explored. The results indicated that the contents of Ti in wheat tissues was reduced about 3-fold and the Ti transfer rate (per day) was reduced about 2 fold at the 1000mgL-1 exposure level of TiO2NPs in biochar amended exposure medium. Transmission electron microscopy (TEM) with elemental mapping confirmed that Ti concentrated in plant tissues in nano-form. The interactive effect of TiO2NPs+biochar amendment on photosynthesis related and gas exchange traits was observed at relatively low TiO2NPs exposure level (200mgL-1), which induced the positive impact on wheat plants proliferation. TiO2NPs alone exposure to wheat also modified the plant's bio-macromolecules profile with the reduction in the assimilation of primary macronutrients, which could affect the food crop nutritional value and quality. X-ray photoelectron spectroscopy (XPS) chemical analysis of biochar+TiO2NPs showed an additional peak, which indicated the binding interaction of NPs with biochar. Moreover, Fourier-transform infrared (FTIR) spectroscopy confirmed that the biochar carboxyl group is the main functionality involved in the bonding process with TiO2NPs. These findings will help for a mechanistic understanding of the role of biochar in the reduction of NPs bioavailability to primary producers of the terrestrial environment.