Toxic Effects Of TiO2 NPs Research Articles

Fructose improves titanium dioxide nanoparticles induced alterations in developmental competence of mouse oocytes

AimsWe investigated the effects of intraperitoneal injections of titanium dioxide nanoparticles (TiO2 NPs, 100 mg/kg) for 5 consecutive days on the developmental competence of murine oocytes. Furthermore, study the effects of TiO2 NPs on antioxidant and oxidative stress biomarkers, as well as their effects on expression of apoptotic and hypoxia inducing factor-1α (HIF1A) protein translation. Moreover, the possible ameliorating effects of intraperitoneal injections of fructose (2.75 mM/ml) was examined.Materials and methodsThirty sexually mature (8–12 weeks old; ~ 25 g body weight) female mice were used for the current study. The female mice were assigned randomly to three treatment groups: Group1 (G1) mice were injected intraperitoneal (ip) with deionized water for 5 consecutive days; Group 2 (G2) mice were injected ip with TiO2 NPs (100 mg/kg BW) for 5 consecutive days; Group 3 (G3) mice were injected ip with TiO2 NPs (100 mg/kg BW + fructose (2.75 mM) for 5 consecutive days.ResultsNano-titanium significantly decreased expression of GSH, GPx, and NO, expression of MDA and TAC increased. The rates of MI, MII, GVBD and degenerated oocytes were significantly less for nano-titanium treated mice, but the rate of activated oocytes was significantly greater than those in control oocytes. TiO2 NPs significantly increased expression of apoptotic genes (BAX, Caspase 3 and P53) and HIF1A. Intraperitoneal injection of fructose (2.75 mM/kg) significantly alleviated the detrimental effects of TiO2 NPs. Transmission electron microscopy indicated that fructose mitigated adverse effects of TiO2 NPs to alter the cell surface of murine oocytes.ConclusionResults of this study suggest that the i/p infusion of fructose for consecutive 5 days enhances development of murine oocytes and decreases toxic effects of TiO2 NPs through positive effects on oxidative and antioxidant biomarkers in cumulus-oocyte complexes and effects to inhibit TiO2-induced increases in expression of apoptotic and hypoxia inducing factors.

The toxicological effects of nano titanium dioxide on target organs and mechanisms of toxicity.

Nano-titanium dioxide (TiO2 NPs) is widely used for its extremely high stability, corrosion resistance, and photocatalytic properties and has penetrated into various fields of production and life. Assessing its toxicity to different organs should be a key part of preclinical toxicity assessment of TiO2 NPs, which is relatively incomprehensive yet. Therefore, this review focuses on the toxic effects of TiO2 NPs on various organs in mammals and biological mechanisms from different organs. The commonality of toxic effects on various target organs reflected in tissue structure damage and dysfunction, such as liver damage and dysfunction; pulmonary fibrosis; and renal impairment (including hematuria and nephritis); damage of brain tissue and neurons; alteration of intestinal villi; and weight loss. And effects on the reproductive system are affected by different sexes, including ovarian dysfunction, testicular development damage, and sperm viability reduction. We believe that the toxic mechanisms of TiO2 NPs in target organs have commonalities, such as oxidative stress, inflammatory responses, and organelle damage. However, different target organ toxicities also have their specificities. TiO2 NPs disturb the intestinal flora and cause undesirable changes in feces products. And in spleen are infiltration of neutrophils and lymphadenopathy and eventually immune deficiency. Although the toxic pathways are different, but there may be a close link between the different toxic pathways. In this article, the main manifestations of the toxic effects of titanium dioxide nanoparticles on major mammalian organs are reviewed, in order to provide basic data for their better application from a medical perspective.

Combined analysis of transcriptomics and metabolomics on the cumulative effect of nano-titanium dioxide on mulberry seedlings.

Titanium dioxide nanoparticles (TiO2 NPs) are among the most widely used inorganic nanomaterials in industry, medicine and food additives. There are increasing concerns regarding their potential risks to plants and the environment. Mulberry trees are widely grown in China due to their high survival rate and ability to aid ecological recovery. Herein, the effects of TiO2 NPs with different concentrations (100, 200, 400 and 800 mg/L) on the growth and physiology of the mulberry tree were systematically evaluated in aspects of physiology, transcriptomics and metabolomics. Results showed that TiO2 NPs could be absorbed by the mulberry sapling root system and be transferred to the plant shoot. This results in the destruction of mulberry sapling root and leaf tissue. Furthermore, the number of chloroplasts and their pigment contents were reduced and the homeostasis of metal ions was disrupted. The toxic effects of TiO2 NPs attenuated the mulberry sapling's stress resistance, the contents of malondialdehyde in 100 mg/L, 200 mg/L 400 mg/L and 800 mg/L treatment groups increased by 87.70%, 91.36%, 96.57% and 192.19% respectively compared with the control group. The transcriptomic data showed that TiO2 NPs treatment mainly affected the expression of genes related to energy synthesis and transport, protein metabolism, and response to stress. Meanwhile, the results of metabolomics showed that 42 metabolites produced significant differences in mulberry, of which 26 differential metabolites were up-regulated in expression and 16 differential metabolites were down-regulated, mainly including metabolic pathways such as secondary metabolite biosynthesis, citric acid cycle, and tricarboxylic acid cycle, and was not conducive to the seed germination and or growth of the mulberry sapling. This study enriches the understanding of the effects of TiO2 NPs on plants and provides a reference for the comprehensive scientific assessment of the potential risks of nanomaterials on plants.

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.

Influence of titanium dioxide nanoparticles on bioaccumulation, antioxidant defense and immune system of Galleria mellonella L.

Nanomaterials of different sizes and diameters are frequently used in various industrial areas, due to the rapid development of nanotechnology. Hence, it leads to toxic effects on the environment and non-target organisms, and adverse effects such as oxidative stress and membrane damage in cells and tissues are occurred. Some biomarkers such as the accumulation of intermediate products, detoxification of the immune system, or xenobiotic are used in the detection of toxic effects of exogenous substances in living organisms. In this study, the effects on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-s-transferase (GST) enzyme activities to determine the toxic effects of TiO2 NPs on antioxidant defense system, acetylcholinesterase (AChE) activity to determine their neurotoxic effects, and total hemocyte count (THC) to determine their effect on the immune system were investigated in model organism Galleria mellonella larvae. It was determined that major amounts of Ti were mostly eliminated through the Malpighian tubules. Moreover, TiO2 NPs in different concentrations caused the formation of reactive oxygen species in G. mellonella and lead to an increase in antioxidant enzymes. Decreases were found in THC due to the TiO2 NP application. As a result, it was concluded that TiO2 NPs caused accumulation in tissues of the model organism G. mellonella, resulting in oxidative stress and has adverse effects on the immune system.

Toxicity assessment of synthesized titanium dioxide nanoparticles in fresh water algae Chlorella pyrenoidosa and a zebrafish liver cell line

This study aims to assess the toxicity of the commonly-spread titanium dioxide nanoparticles (TiO2 NPs) by evaluating the exposure impact of the particles on both freshwater algae Chlorella pyrenoidosa and zebrafish liver cell line (ZFL), the two common in vitro models in toxicological studies. To compare the toxic effects of TiO2 NPs with different physiochemical properties, three types of manufactured TiO2 were used: bulk TiO2, Degussa P25 TiO2, and ultrafine TiO2 NPs. Both short and long-term biological responses of green algae, such as the effect on the cell growth rate, pigment autofluorescence, and esterase activity were investigated. The dosage, physical property of TiO2 particles, and their interactions with algal cells affect cellular growth, especially after short-term exposure. The hydrodynamic size plays a critical role in determining the acute toxicity to C. pyrenoidosa in terms of autofluorescence and esterase activity, while all types of TiO2 NPs show toxic effects after exposure for 14 days. However, this observation is not seen when studying the effect of introduced particles in ZFL, for the precipitated Degussa P25 TiO2 showed the highest cellular inhibition. Interestingly, despite the obvious overall toxicity toward C. pyrenoidosa, the photocatalytical properties of TiO2 NPs may contribute to the enhanced photosynthesis in the low concentration range (<40 µg mL−1). Overall, we found that the physical interactions between TiO2 particles and the cells, particles’ size and dispersibility play critical role in the cytotoxic effect for both algal and ZFL cells, while the photocatalytical properties of TiO2 particles may produce mixed effects on the cytotoxicity of green algae.

In Vitro Interactions of TiO2 Nanoparticles with Earthworm Coelomocytes: Immunotoxicity Assessment.

Titanium dioxide nanoparticles (TiO2 NPs) are manufactured worldwide. Once they arrive in the soil environment, they can endanger living organisms. Hence, monitoring and assessing the effects of these nanoparticles is required. We focus on the Eisenia andrei earthworm immune cells exposed to sublethal concentrations of TiO2 NPs (1, 10, and 100 µg/mL) for 2, 6, and 24 h. TiO2 NPs at all concentrations did not affect cell viability. Further, TiO2 NPs did not cause changes in reactive oxygen species (ROS) production, malondialdehyde (MDA) production, and phagocytic activity. Similarly, they did not elicit DNA damage. Overall, we did not detect any toxic effects of TiO2 NPs at the cellular level. At the gene expression level, slight changes were detected. Metallothionein, fetidin/lysenin, lumbricin and MEK kinase I were upregulated in coelomocytes after exposure to 10 µg/mL TiO2 NPs for 6 h. Antioxidant enzyme expression was similar in exposed and control cells. TiO2 NPs were detected on coelomocyte membranes. However, our results do not show any strong effects of these nanoparticles on coelomocytes at both the cellular and molecular levels.

Toxic effects of TiO2 NPs in the blood-milk barrier of the maternal dams and growth of offspring

Titanium dioxide nanoparticles (TiO2 NPs) are amongst the most frequently used nanomaterial in everyday consumer products, and their widespread applications have raised concerns of the consequent deleterious effects on human health, particularly to vulnerable populations, such as lactating females remains elusive. Therefore, this study was initiated to investigate the detrimental effects and toxic mechanisms induced by TiO2 NPs in maternal dams and offspring during the lactation period. Dams were randomly divided into three groups. The water (Control; Group I) and TiO2 NPs (100 mg/kg; Group II) were orally administered from postnatal day 1–20, respectively. The results indicated that TiO2 NPs could cause toxicity in the dams, such as pathological damages to mammary gland tissues. The excessive accumulation of TiO2 NPs could induce oxidative stress in the mammary gland, leading to the dysfunctional blood-milk barrier; besides, TiO2 NPs could also be transferred to offspring via breastfeeding, causing abnormal development of infant. We further accessed the possible underlying molecular mechanism; for this, we orally administered TiO2 NPs with vitamin E (100 mg/kg; Group III). The results revealed that toxicity induced by TiO2 NPs was rescued. Collectively, this study presented the deleterious pathological effects of oral exposure to TiO2 NPs in the mammary gland tissues and blood-milk barrier via the production of reactive oxygen species (ROS) in dams and developmental concerns in offspring. However, the administration of VE could mitigate the toxic effects induced by the TiO2 NPs.

Melatonin protects sperm cells of Capoeta trutta from toxicity of titanium dioxide nanoparticles.

In this study, it was aimed to determine the protective effects of melatonin (0.01, 0.1, and 1mM) against 10mg/L titanium dioxide nanoparticles (TiO2-NPs) on kinematic and oxidative indices in the sperm cells of Capoeta trutta. Therefore, TiO2 nanoparticles were synthesized primarily within the scope of the study. The synthesized nanoparticles were characterized by structurally different techniques. Then, melatonin and TiO2 were applied to Capoeta trutta sperm cells by in vitro. According to our data, all doses of melatonin showed protective effects on all velocities of sperm cells such as the straight line velocity (VSL), the curvilinear velocity (VCL), and the angular path velocity (VAP) against TiO2-NPs, while 0.1 and 1mM doses of melatonin improved the VSL value. Although TiO2-NPs increased total glutathione (tGSH), malondialdehyde (MDA) lipid peroxidation, and superoxide dismutase (SOD) compared to the control group, there were positive treatment effects for all doses of melatonin on antioxidant capacity of sperm cells. At the end of this research, it is suggested that over 0.1mM dose of melatonin improves the velocity of sperm cells and it plays a protective role against the toxic effects of TiO2-NPs.

Titanium dioxide nanoparticles induce endothelial cell apoptosis via cell membrane oxidative damage and p38, PI3K/Akt, NF-κB signaling pathways modulation

BackgroundTitanium dioxide nanoparticles (TiO2 NPs) are widely used nanoparticles. Despite, several studies investigated the toxic effects of TiO2 NPs on HUVECs, the results are contradictory and the possible underlying mechanisms remain unclear. MethodsIn the present study, we conducted an in vitro study to re-evaluate the possible toxic effects of TiO2 NPs on HUVECs including cell viability, lipids peroxidation, intracellular signaling pathways and nitric oxide syntheses enzymes. ResultsOur results demonstrated that, TiO2 NPs were internalized to HUVECs and induce intracellular reactive oxygen species production and cell membrane oxidative damage at the higher concentration. TiO2 NPs induce IKKα/β and Akt phosphorylation and p38 dephosphorylation. After 24 h treatment, pro-inflammatory cytokines, adhesion molecules and chemokine upregulated significantly. TiO2 NPs have no significant effects on eNOS enzymatic activation and iNOS gene expression. At cellular level, apoptosis is the main process that occur in response to TiO2 NPs treatment. HUVECs pretreatment with N-acetyl-l-cysteine (NAC) ameliorate the toxic effects of TiO2 NPs that indicate the oxidative stress is essential in TiO2 NPs -induced toxicity. Total antioxidant capacity show a trend to increase in response to TiO2 NPs exposure. ConclusionsTaken together, this study confirmed the effects of TiO2 NPs on endothelial cells and proposed multiple underlying mechanisms including cell membrane oxidative damage and intracellular processes.

Different effects of titanium dioxide nanoparticles instillation in young and adult mice on DNA methylation related with lung inflammation and fibrosis

Wide use of titanium dioxide nanoparticles (TiO2 NPs) as white pigments induces unintentionally release in environment which increases concerns about their adverse health effects on respiratory system. So it is crucial to get a deep understanding of the disease process and molecular mechanism. Epigenetic mechanisms, such as DNA methylation, have been found to play a role in the development of lung diseases by affecting expression of key genes. In addition, there could be potential different toxic effects of TiO2 NPs between young and adult. Thus, the comparative toxicity of TiO2 NPs in 5-week (young) and 10-week (adult) old NIH mice is investigated in this study following nasal inhalation of TiO2 NPs at dose of 20 mg/kg (body weight)/day for 30 days. Global DNA methylation and hydroxymethylation in lung were measured. Promoter methylation of inflammatory genes (IFN-γ and TNF-α) and tissue fibrosis gene (Thy-1) were determined. Additional, RNA-sequencing runs were performed on the pulmonic libraries. We found the induced pulmonary inflammation and fibrosis were more severe in young mice. Decreased global methylation and hydroxymethylation were only found in the young group. The altered methylation in promoter of TNF-α and Thy-1 were found to play a role in the inflammatory response and fibration. RNA-sequencing showed that in pathways in cancer expression of 197 genes was up-regulated in the young mice more that in the adult mice. All these results suggested that the young ages are more sensitive to TiO2 NP exposure and the potential of abnormal DNA methylation might be used as biomarkers of both exposure and disease development.

Toxic Effects of TiO₂ NPs on Zebrafish.

Titanium dioxide nanoparticles (TiO2 NPs) have become a widely used nanomaterial due to the photocatalytic activity and absorption of ultraviolet light of specific wavelengths. This study investigated the toxic effects of rutile TiO2 NPs on zebrafish by examining its embryos and adults. In the embryo acute toxicity test, exposure to 100 mg/L TiO2 NPs didn’t affect the hatching rate of zebrafish embryos, and there was no sign of deformity. In the adult toxicity test, the effects of TiO2 NPs on oxidative damage in liver, intestine and gill tissue were studied. Enzyme linked immunosorbent assay (ELISA) and fluorescence-based quantitative real-time reverse transcription PCR (qRT-PCR) were used to detect the three antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione S transferase (GSTs) in the above mentioned zebrafish organs at protein and gene levels. The results showed that long-term exposure to TiO2 NPs can cause oxidative damage to organisms; and compared with the control group, the activity of the three kinds of enzyme declined somewhat at the protein level. In addition, long-term exposure to TiO2 NPs could cause high expression of CAT, SOD and GSTs in three organs of adult zebrafish in order to counter the adverse reaction. The effects of long-term exposure to TiO2 NPs to adult zebrafish were more obvious in the liver and gill.

Influence of differently functionalized polystyrene microplastics on the toxic effects of P25 TiO2 NPs towards marine algae Chlorella sp.

Increased utilization of titanium dioxide nanoparticles (TiO2 NPs) for commercial as well as industrial purposes resulted in the accumulation of nanoparticles in the marine system. Microplastics being an emerging secondary pollutant in the marine ecosystem have an impact on the toxic effects of TiO2 NPs which has not been evaluated up to date. So it is important to assess the toxic effects of both these pollutants on the marine environment. The present study examines the impact of differently functionalized microplastics on the toxic effects of P25 TiO2 NPs to marine algae Chlorella sp. The tendency of nanoparticles to undergo aggregation in artificial seawater was observed with increase in time. The median effective concentration for TiO2 NPs was found to be 81 μM which indicates higher toxic effects of NPs toward algae. In contrast, microplastics irrespective of their difference in functionalization had minimal toxic effect of about 15% at their higher concentration tested, 1000 mg L−1. Plain and aminated polystyrene microplastics enhanced the TiO2 NPs toxicity which was further validated with oxidative stress determination studies like reactive oxygen species and lipid peroxidation assays. Negatively charged carboxylated polystyrene microplastics decreased the TiO2 NPs toxicity with possible hetero-aggregation between TiO2 NPs and microplastics in the system. The toxicity data obtained for the mixture was further corroborated with Abbott’s mathematical model.

Nano-TiO2 enhances biofilm formation in a bacterial isolate from activated sludge of a waste water treatment plant

TiO2 NPs is one of the major components of paints and sunscreens and also acts as a catalyst for waste water treatment. The study demonstrates the toxic effects of TiO2 NPs on an anaerobic bacterium, Macrococcus caseolyticus, isolated from the activated sludge of a waste water treatment facility. The cytotoxicity assessment under UVA, visible light, and dark conditions revealed a dose- and exposure-dependent reduction in viability. The examination of cytotoxicity was performed with membrane permeability assessment through LDH (Lactate dehydrogenase) detection. The formation of exopolymeric substances (EPS) was observed to be dose-dependent, and maximum EPS release was noted under UVA condition. The scanning electron microscopy described the aggregation tendency of biofilm to be more pronounced under UVA condition when treated with TiO2 NPs as compared to the control biofilm. Uptake of TiO2 NPs by the biofilm indicated possible remediation of the NPs in waste water by these organisms.

In Vitro Analyses of Effect of Light on Toxicity of Titanium Dioxide Nanoparticles to Tetrahymena pyriformis Using Fourier Transform Infrared Spectra

ABSTRACT The wide application of titanium dioxide nanoparticles (TiO2 NPs) has caused a large number of TiO2 NPs to be released into the water environment without treatment, which would inevitably result in unexpected toxic damage to aquatic animals. The objects of this research were to discuss the toxic effects of TiO2 NPs to Tetrahymena pyriformis (T. pyriformis) under dark and light conditions. The Fourier transform infrared (FTIR) spectra were utilized to investigate the biochemical constituent changes of T. pyriformis under the exposure of TiO2 NPs. The results showed that illumination had little effect on the cell numbers of T. pyriformis after 24 hr exposure at 5 mg/L of TiO2 concentration. However, the cell viability of TiO2 NP–exposed T. pyriformis under light illumination (81.4%) decreased compared with that in the dark environment (96.1%). The FTIR results showed that the typical absorption band of the CH2 asymmetric stretching vibration shifted from 2924.64 to 2925.49 cm−1 in the dark, which indicated an increase in membrane fluidity without illumination. A decreased intensity (p < 0.05) was observed in amide I and amide II from 98.57 ± 9.62 and 41.88 ± 3.63 to 75.65 ± 4.07 and 25.25 ± 1.12 in the irradiated T. pyriformis, respectively, which suggested that the coexistence of TiO2 NPs and light could induce an obvious decrease of protein. In the light condition, the overproduction of ROS led to the breakdown of balance of the oxidative/antioxidative system, resulting in the lipid peroxidation and the death of cells. The results further reveal that TiO2 NPs under light conditions are more toxic than in the dark.

Imbalance between oxidative and antioxidative systems: Toward an understanding of visible light-induced titanium dioxide nanoparticles toxicity

The broad application of titanium dioxide nanoparticles (TiO2 NPs) has resulted in the release of substantial quantities of untreated TiO2 NPs into aquatic systems, which serve as the terminal sink for nanomaterials. These TiO2 NPs may induce some unexpected toxic effects to aquatic systems. The objectives of this research were to evaluate toxic effects of low dosage TiO2 NPs on Tetrahymena pyriformis under visible-light illumination conditions and further discuss possible mechanisms. The results showed that TiO2 NPs accumulated as aggregates in cytosolic vesicles of T. pyriformis. Cell numbers and viability of TiO2 NPs-exposed groups decreased to (20.2±1.8)% and (17.3±1.9)% after 24h continuous 12000 Lx illumination. Compared with the dark control, the intracellular reactive oxygen species (ROS) levels increased (1.9-fold) by the combination of 5mgL−1 TiO2 NPs and 12000 Lx illumination. Even incubation in the dark for 6h after 12h illumination, superoxide dismutase (SOD) activity of TiO2 NPs exposed groups still maintained at the high level (about 3.9-fold of dark control). Meanwhile, illumination-induced TiO2 NPs led to a reduction of scavenging hydroxyl radicals (OH) activity with an average of (14.3±6.5)%. Under illumination conditions, overproduction of reactive oxygen species (ROS) by TiO2 NPs exceeded the scavenging capability of T. pyriformis and then led to the breakdown of oxidative/anti-oxidative systems, further resulting in cell growth delay and mitochondria dysfunction. All the results revealed that via visible light excitation, oxidative injury may be responsible for the toxic effects of TiO2 NPs on T. pyriformis.