Ti3C2 nanosheet-induced autophagy derails ovarian functions.

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. RESULTS: We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. CONCLUSION: Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.

Changes in life history parameters and expression of key genes of Brachionus plicatilis exposed to a combination of organic and inorganic ultraviolet filters.

The increasing use of ultraviolet filters has become an emerging contaminant on the coast, posing potential ecological risks. Rotifers are essential components of marine ecosystems, serving as an association between primary producers and higher-level consumers. These organisms frequently encounter ultraviolet filters in coastal waters. This study aimed to assess the comprehensive effects of organic ultraviolet filters, specifically 2-ethylhexyl-4-methoxycinnamate (EHMC), and inorganic ultraviolet filters, namely, titanium dioxide nanoparticles (TiO2 NPs), on the rotifer Brachionus plicatilis. We exposed B. plicatilis to multiple combinations of different concentrations of EHMC and TiO2 NPs to observe changes in life history parameters and the expression of genes related to reproduction and antioxidant responses. Our findings indicated that increased EHMC concentrations significantly delayed the age at first reproduction, reduced the total offspring, and led to considerable alterations in the expression of genes associated with reproduction and stress. Exposure to TiO2 NPs resulted in earlier reproduction and decreased total offspring, although these changes were not synchronised in gene expression. The two ultraviolet filters had a significant interaction on the age at first reproduction and the total offspring of rotifer, with these interactions extending to the first generation. This research offers new insights into the comprehensive effects of different types of ultraviolet filters on rotifers by examining life history parameters and gene expression related to reproduction and stress, highlighting the importance of understanding the impacts of sunscreen products on zooplankton health.

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

AIMS: We 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 METHODS: Thirty 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. RESULTS: Nano-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. CONCLUSION: Results 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.

Comparative investigation on chemical and green synthesized titanium dioxide nanoparticles against chromium (VI) stress eliciting differential physiological, biochemical, and cellular attributes in Helianthus annuus L.

Nanotechnology is a new scientific area that promotes unique concepts to comprehend the optimal mechanics of nanoparticles (NPs) in plants under heavy metal stress. The present investigation focuses on effects of synthetic and green synthesized titanium dioxide nanoparticles (TiO2 NPs and gTiO2 NPs) against Cr(VI). Green TiO2 NPs have been produced from plant leaf extract (Ricinus communis L.). Synthesis was confirmed employing an array of optical spectroscopic and electron microscopic techniques. Chromium strongly accelerated H2O2 and MDA productions by 227 % and 266 % at highest chromium concentration (60 mg/kg of soil), respectively, and also caused DNA damage, and decline in photosynthesis. Additionally, anomalies were observed in stomatal cells with gradual increment in chromium concentrations. Conversely, foliar applications of TiO2 NPs and gTiO2 NPs considerably mitigated chromium stress. Sunflower plants treated with modest amounts of green TiO2 NPs had significantly better growth index compared to chemically synthesized ones. Principal component analysis highlighted the variations among photosynthetic attributes, oxidative stress markers, and antioxidant defense systems. Notably, gTiO2 supplementation to the Cr(VI) strained plants minimized PC3 production which is a rare report so far. Conclusively, gTiO2 NPs have been identified to be promising nano-based nutrition resource for farming applications.

Nano-titanium dioxide exacerbates the harmful effects of perfluorooctanoic acid on the health of mussels.

Exposing marine organisms to contemporary contaminants, such as perfluorooctanoic acid (PFOA) and nano-titanium dioxide (nano-TiO2), can induce multifaceted physiological consequences. Our investigation centered on the responses of the mussel, Mytilus coruscus, to these agents. We discerned pronounced disruptions in gill filament connections, pivotal structures for aquatic respiration, suggesting compromised oxygen uptake capabilities. Concurrently, the respiratory rate exhibited a marked decline, indicating a respiratory distress. Furthermore, the mussels' clearance rate, a metric of their filtration efficacy, diminished, suggesting the potential for bioaccumulation of deleterious substances. Notably, the co-exposure of PFOA and nano-TiO2 exhibits interactive effects on the physiological performance of the mussels. The mussels' digestive performance waned in the face of heightened PFOA and nano-TiO2 concentrations, possibly hampering nutrient assimilation and energy accrual. This was mirrored in the noticeable contraction of their energy budget, suggesting long-term growth repercussions. Additionally, the dysregulation of the gut microbiota and the reduction in its diversity further confirm alterations in intestinal homeostasis, subsequently impacting its physiological functions and health. Collectively, these findings underscore the perils posed by escalated PFOA and nano-TiO2 levels to marine mussels, accentuating the need for a deeper understanding of nanoparticle-pollutant synergies in marine ecosystems.

Metal nanoparticle-induced effects on green toads (Amphibia, Anura) under climate change: conservation implications.

The toxicity of aluminum oxide (Al2O3), copper oxide (CuO), iron oxide (Fe3O4), nickel oxide (NiO), zinc oxide (ZnO), and titanium dioxide (TiO2) nanoparticles (NPs) on amphibians and their interaction with high temperatures, remain unknown. In this study, we investigated the survival, developmental, behavioral, and histological reactions of Bufotes viridis embryos and larvae exposed to different NPs for a duration of 10 days, using lethal concentrations (LC25%, LC50%, and LC75% mg/L) under both ambient (AT: 18 °C) and high (HT: 21 °C) temperatures. Based on LC, NiONPs > ZnONPs > CuONPs > Al2O3NPs > TiO2NPs > Fe3O4NPs showed the highest mortality at AT. A similar pattern was observed at HT, although mortality occurred at lower concentrations and Fe3O4NPs were more toxic than TiO2NPs. The results indicated that increasing concentrations of NPs significantly reduced hatching rates, except for TiO2NPs. Survival rates decreased, abnormality rates increased, and developmental processes slowed down, particularly for NiONPs and ZnONPs, under HT conditions. However, exposure to low concentrations of Fe3O4NPs for up to 7 days, CuONPs for up to 72 h, and NiO, ZnONPs, and TiO2NPs for up to 96 h did not have a negative impact on survival compared with the control group under AT. In behavioral tests with larvae, NPs generally induced hypoactivity at AT and hyperactivity at HT. Histological findings revealed liver and internal gill tissue lesions, and an increase in the number of melanomacrophage centers at HT. These results suggest that global warming may exacerbate the toxicity of metal oxide NPs to amphibians, emphasizing the need for further research and conservation efforts in this context.

Titanium dioxide nanoparticles oral exposure induce osteoblast apoptosis, inhibit osteogenic ability and increase lipogenesis in mouse.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used in food, paint, coating, cosmetic, and composite orthodontic material. As a common food additive, TiO2-NPs can accumulate in various organs of human body, but the effect and underlying mechanism of bone remain unclear. Here mice were exposed to TiO2-NPs by oral gavage, and histological staining of femoral sections showed that TiO2-NPs reduced bone formation and enhanced osteoclast activity and lipogenesis, contributing to decreased trabecula bone. Transmission electron microscope (TEM) as well as biochemical and flow cytometry analysis of osteoblast exhibited that TiO2-NPs accumulated in osteoblast cytoplasm and impaired mitochondria ultrastructure with increased reactive oxygen species (ROS) and lipid hyperoxide, resulting in osteoblast apoptosis. In terms of mechanism, TiO2-NPs treatment inhibited expression of AKT and then increased pro-apoptotic protein Bax expression which was failure to form heterodimers with decreased anti-apoptotic Bcl-2, activating downstream Caspase-9 and Caspase-3 and inducing apoptosis. Additionally, TiO2-NPs suppressed Wnt3a level and then activated anti-Glycogen synthesis kinase (GSK-3ß) phosphorylation, and ultimately resulted in degradation of ß-catenin which down-regulated Runt-related transcription factor 2 (Runx2) and Osterix, inhibiting expression of osteogenic related proteins. Together, these results revealed that exposure of TiO2-NPs induced apoptosis and inhibited osteoblast differentiation through suppressing PI3K/AKT and Wnt/ß-catenin signaling pathways, resulting in reduction of trabecula bone.

Life cycle exposure to titanium dioxide nanoparticles (TiO2-NPs) induces filial toxicity and population decline in the nematode Caenorhabditis elegans.

Titanium dioxide nanoparticle (TiO2-NP) exposure has raised significant concern due to their potential toxicity and adverse ecological impacts. Despite their ubiquitous presence in various environmental compartments, the long-term consequences of TiO2-NPs remain poorly understood. In this study, we combined data of in vivo toxicity and modeling to investigate the potential negative impacts of TiO2-NP exposure. We employed the nematode Caenorhabditis elegans, an environmental organism, to conduct a full life cycle TiO2-NP toxicity assays. Moreover, to assess the potential impact of TiO2-NP toxicity on population dynamics, we applied a stage-constructed matrix population model (MPM). Results showed that TiO2-NPs caused significant reductions in reproduction, survival, and growth of parental C. elegans (P0) at the examined concentrations. Moreover, these toxic effects were even more pronounced in the subsequent generation (F1) when exposed to TiO2-NPs. Furthermore, parental TiO2-NP exposure resulted in significant toxicity in non-exposed C. elegans progeny (TiO2-NPs free), adversely affecting their reproduction, survival, and growth. MPM analysis revealed decreased transition probabilities of surviving (Pi), growth (Gi), and fertility (Fi) in scenarios with TiO2-NP exposure. Additionally, the population growth rate (λmax) was found to be less than 1 in both P0 and F1, indicating a declining population trend after successive generations. Sensitivity analysis pinpointed L1 larvae as the most vulnerable stage, significantly contributing to the observed population decline in both P0 and F1 generations under TiO2-NP exposure. Our findings provide insight into the potential risk of an environmental organism like nematode by life cycle exposure to TiO2-NPs.

Modulation efficiency of clove oil nano-emulsion against genotoxic, oxidative stress, and histological injuries induced via titanium dioxide nanoparticles in mice.

Titanium dioxide nanoparticles (TiO2-NPs) have found wide applications in medical and industrial fields. However, the toxic effect of various tissues is still under study. In this study, we evaluated the toxic effect of TiO2-NP on stomach, liver, and kidney tissues and the amelioration effect of clove oil nanoemulsion (CLV-NE) against DNA damage, oxidative stress, pathological changes, and the apoptotic effect of TiO2-NPs. Four groups of male mice were subjected to oral treatment for five consecutive days including, the control group, the group treated with TiO2-NPs (50 mg/kg), the group treated with (CLV-NE) (5% of the MTD), and the group treated with TiO2-NPs plus CLV-NE. The results revealed that the treatment with TiO2-NPs significantly caused DNA damage in the liver, stomach, and kidney tissues due to increased ROS as indicated by the reduction of the antioxidant activity of SOD and Gpx and increased MDA level. Further, abnormal histological signs and apoptotic effect confirmed by the significant elevation of p53 expression were reported after TiO2-NPs administration. The present data reported a significant improvement in the previous parameters after treatment with CLV-NE. These results showed the collaborative effect of the oils and the extra role of nanoemulsion in enhancing antioxidant effectiveness that enhances its disperse-ability and further promotes its controlled release. One could conclude that CLV-NE is safe and can be used as a powerful antioxidative agent to assess the toxic effects of the acute use of TiO2-NPs.

Combined effects of pentachlorophenol and nano-TiO2 with different sizes on antioxidant, digestive, and immune responses of the swimming crab Portunus trituberculatus.

Marine nano-titanium dioxide (nano-TiO2) and pentachlorophenol (PCP) pollution are escalating concerns in coastal areas. This study investigated the combined effects of continuous exposure to nano-TiO2 (25 nm, 100 nm) and PCP (0, 1, 10 µg/L) for 28 days on the antioxidant, digestive, and immune abilities of the swimming crab Portunus trituberculatus. Compared with the control group, the interaction between nano-TiO2 and PCP was significantly higher than exposure to a single stressor, with a pronounced decrease in amylase activity observed due to the reducing nano-TiO2 particle sizes. Resulting in increased MDA and SOD activity. The expression levels of Toll4, CSP3, and SER genes in crab hemolymph showed perturbations following exposure to nano-TiO2 and PCP. In summary, according to the results of CAT, GPX, PES and AMS enzyme activities, it was concluded that compared to the larger particle size (100 nm), the single stress of nano-TiO2 at a smaller particle size (25 nm) and co-stress with PCP have more significant impacts on P. trituberculatus. However, the potential physiological regulation mechanism of the interaction between these pollutants remains elusive and requires further study.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles induce mitochondrial permeability and cardiac damage after oral exposure in rats.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are found in diverse products for human use. E171 is used as whitening agent in food and cosmetics, and ZnO NPs in food packaging. Their potential multi-organ toxicity has raised concerns on their safety. Since mitochondrial dysfunction is a key aspect of cardio-pathologies, here, we evaluate the effect of chronic exposure to E171 and ZnO NPs in rats on cardiac mitochondria. Changes in cardiac electrophysiology and body weight were measured. E171 reduced body weight more than 10% after 5 weeks. Both E171 and ZnO NPs increased systolic blood pressure (SBP) from 110-120 to 120-140 mmHg after 45 days of treatment. Both NPs altered the mitochondrial permeability transition pore (mPTP), reducing calcium requirement for permeability by 60% and 93% in E171- and ZnO NPs-exposed rats, respectively. Treatments also affected conformational state of adenine nucleotide translocase (ANT). E171 reduced the binding of EMA to Cys 159 in 30% and ZnO NPs in 57%. Mitochondrial aconitase activity was reduced by roughly 50% with both NPs, indicating oxidative stress. Transmission electron microscopy (TEM) revealed changes in mitochondrial morphology including sarcomere discontinuity, edema, and hypertrophy in rats exposed to both NPs. In conclusion, chronic oral exposure to NPs induces functional and morphological damage in cardiac mitochondria, with ZnO NPs being more toxic than E171, possibly due to their dissociation in free Zn2+ ion form. Therefore, chronic intake of these food additives could increase risk of cardiovascular disease.

Viability and Proliferation Assessment of Gingival Fibroblasts Cultured on Silver Nanoparticle-Doped Ti-6Al-4V Surfaces.

PURPOSE: To investigate the biocompatibility of silver nanoparticle (AgNP)-doped Ti-6Al-4V surfaces by evaluating the viability and proliferation rate of human gingival fibroblasts (HGFs)-as the dominant cells of peri-implant soft tissues-seeded on the modified surfaces. MATERIALS AND METHODS: AgNPs (sizes 8 nm and 30 nm) were incorporated onto Ti-6Al-4V specimen surfaces via electrochemical deposition, using colloid silver dispersions with increasing AgNP concentrations of 100 ppm, 200 ppm, and 300 ppm. One control and six experimental groups were included in the study: (1) control (Ti-6Al-4V), (2) 8 nm/100 ppm, (3) 8 nm/200 ppm, (4) 8 nm/300 ppm, (5) 30 nm/100 ppm, (6) 30 nm/200 ppm, and (7) 30 nm/300 ppm. HGF cell primary cultures were isolated from periodontally healthy donor patients and cultured in direct contact with the group specimens for 24 and 72 hours. The cytotoxicity of AgNP-doped Ti-6Al-4V specimens toward HGF was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and BrdU (5-bromo-2'-deoxyuridine) assay tests. Calcein AM and ethidium homodimer (EthD-1) fluorescent stains were used to determine the live and dead cells. The morphology and attachment properties of the HGFs were determined via scanning electron microscopy (SEM). RESULTS: Energy dispersive x-ray (EDX) analysis confirmed the presence of AgNPs on the specimens. The MTT test revealed that AgNPs of both sizes and all concentrations presented a decreased cellular metabolic activity compared to the control discs. All concentrations of both sizes of AgNPs affected the cell proliferation rate compared to the control group, as revealed by the BrdU assay. Overall, cytotoxicity of the modified Ti-6Al-4V surfaces depended on cell exposure time. Observation via confocal microscopy confirmed the results of the MTT and BrdU assay tests. Specifically, most cells remained alive throughout the 72-hour culture period. SEM images revealed that adjacent cells form bonds with each other, creating confluent layers of conjugated cells. CONCLUSIONS: The findings of the present study indicate that Ti-6Al-4V surfaces modified with 8 nm and 30 nm AgNPs at concentrations of 100 ppm, 200 ppm, and 300 ppm do not produce any serious cytotoxicity toward HGFs. The initial arrest of the HGF proliferation rate recovered at 72 hours. These results on the antibacterial activity against common periodontal pathogens, in combination with the results found in a previous study by the same research group, suggest that AgNP-doped Ti-6Al-4V surfaces are potential candidates for use in implant abutments for preventing peri-implant diseases.

Calycosin alleviates titanium particle-induced osteolysis by modulating macrophage polarization and subsequent osteogenic differentiation.

Periprosthetic osteolysis (PPO) caused by wear particles is one of the leading causes of implant failure after arthroplasty. Macrophage polarization imbalance and subsequent osteogenic inhibition play a crucial role in PPO. Calycosin (CA) is a compound with anti-inflammatory and osteoprotective properties. This study aimed to evaluate the effects of CA on titanium (Ti) particle-induced osteolysis, Ti particle-induced macrophage polarization and subsequent osteogenic deficits, and explore the associated signalling pathways in a Ti particle-stimulated calvarial osteolysis mouse model using micro-CT, ELISA, qRT-PCR, immunofluorescence and western blot techniques. The results showed that CA alleviated inflammation, osteogenic inhibition and osteolysis in the Ti particle-induced calvarial osteolysis mouse model in vivo. In vitro experiments showed that CA suppressed Ti-induced M1 macrophage polarization, promoted M2 macrophage polarization and ultimately enhanced osteogenic differentiation of MC3T3-E1 cells. In addition, CA alleviated osteogenic deficits by regulating macrophage polarization homeostasis via the NF-κB signalling pathway both in vivo and in vitro. All these findings suggest that CA may prove to be an effective therapeutic agent for wear particle-induced osteolysis.

The combined neurotoxicity of DBP and nano-TiO2 in embryonic zebrafish (Danio rerio) revealed by oxidative activity, neuro-development genes expression and metabolomics changes.

Dibutyl phthalate (DBP) is a commonly used plasticizer that is frequently detected in water samples due to its widespread use. Titanium dioxide nanoparticles (n-TiO2) have been found to enhance the harmful effects of organic contaminants by increasing their bioavailability in aquatic environments. However, the combined toxic effects of DBP and n-TiO2 on aquatic organisms remain unclear. This study aimed to investigate the neurotoxicity of DBP and n-TiO2 synergistic exposure during the early life stage of zebrafish. The results of the study revealed that co-exposure of DBP and n-TiO2 led to an increase in deformities and a significant reduction in the active duration of zebrafish larvae. Furthermore, the co-exposure of DBP and n-TiO2 resulted in elevated levels of oxidative stress and altered gene expression related to neurodevelopment and apoptosis. Notably, n-TiO2 exacerbated the oxidative damage and apoptosis induced by DBP alone exposure. Additionally, co-exposure of the 1.0 mg/L DBP and n-TiO2 significantly affected the expression of genes associated with neurodevelopment. Moreover, disturbances in amino acid metabolism and interference with lipid metabolism were observed as a result of DBP and n-TiO2 co-exposure. In general, n-TiO2 aggravated the neurotoxicity of DBP in the early life stage of zebrafish by increasing oxidative stress, apoptosis, and disrupting amino acid synthesis and lipid metabolism. Therefore, it is essential to consider the potential risks caused by DBP and nanomaterials co-existence in the aquatic environment.

Chronic toxicity of core-shell SiC/TiO2 (nano)-particles to Daphnia magna under environmentally relevant food rations in the presence of humic acid.

To date, research on the toxicity and potential environmental impacts of nanomaterials has predominantly focused on relatively simple and single-component materials, whilst more complex nanomaterials are currently entering commercial stages. The current study aimed to assess the long-term and size-dependent (60 and 500 nm) toxicity of a novel core-shell nanostructure consisting of a SiC core and TiO2 shell (SiC/TiO2, 5, 25, and 50 mg L-1) to the common model organism Daphnia magna. These novel core-shell nanostructures can be categorized as advanced materials. Experiments were conducted under environmentally realistic feeding rations and in the presence of a range of concentrations of humic acid (0.5, 2, 5, and 10 mg L-1 TOC). The findings show that although effect concentrations of SiC/TiO2 were several orders of magnitude lower than the current reported environmental concentrations of more abundantly used nanomaterials, humic acid can exacerbate the toxicity of SiC/TiO2 by reducing aggregation and sedimentation rates. The EC50 values (mean ± standard error) based on nominal SiC/TiO2 concentrations for the 60 nm particles were 28.0 ± 11.5 mg L-1 (TOC 0.5 mg L-1), 21.1 ± 3.7 mg L-1 (TOC 2 mg L-1), 18.3 ± 5.4 mg L-1 (TOC 5 mg L-1), and 17.8 ± 2.4 mg L-1 (TOC 10 mg L-1). For the 500 nm particles, the EC50 values were 34.9 ± 16.5 mg L-1 (TOC 0.5 mg L-1), 24.8 ± 5.6 mg L-1 (TOC 2 mg L-1), 28.0 ± 10.0 mg L-1 (TOC 5 mg L-1), and 23.2 ± 4.1 mg L-1 (TOC 10 mg L-1). We argue that fate-driven phenomena are often neglected in effect assessments, whilst environmental factors such as the presence of humic acid may significantly influence the toxicity of nanomaterials.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Doping zinc oxide and titanium dioxide nanoparticles with gold induces additional oxidative stress, membrane damage, and neurotoxicity in Mytilus galloprovincialis: Results from a laboratory bioassay.

BACKGROUND: While previous studies have provided insights into the effects of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles (NPs) on aquatic organisms, there is still a substantial amount of information lacking about the possible effects of their doped counterparts. The goal of the current work was to address this gap by examining Mytilus galloprovincialis reaction to exposure to doped and undoped nanoparticles. METHODS: Two concentrations (50 or 100 µg/L) of undoped ZnO and TiO2 NPs, as well as their gold (Au) doped counterparts, were applied on mussels for 14 days, and the effects on biomarkers activities in digestive glands and gills were assessed by spectrophotometry. RESULTS: The NPs were quasi-spherical in shape (below 100 nm), stable in seawater, and with no aggregation for both doped and undoped forms. Analytical results using inductively coupled plasma atomic emission spectroscopy indicated the uptake of NPs in mussels. Furthermore, it was found that biometal dyshomeostasis could occur following NP treatment and that doping the NPs aggravated this response. At the biochemical level, exposure to undoped NPs caused membrane damage, neurotoxic effect, and changes in the activities in the gills and digestive glands of superoxide dismutase, catalase, and glutathione-S-transferase, in a concentration and organ-dependent manner. CONCLUSION: Doping ZnO NPs and TiO2NPs with Au induced additional oxidative stress, membrane damage, and neurotoxicity in mussels.

Aggravated visual toxicity in zebrafish larvae upon co-exposure to titanium dioxide nanoparticles and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate.

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of ßB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates.

Silicon and titanium nanoparticles modulated drought and chromium toxicity by adjusting physio-biochemical attributes and fatty acid profiles of black cumin (Nigella sativa L.).

Drought and chromium (Cr) stress are the main environmental issues affecting plant performance. Although the positive effects of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanoparticles (NPs) are used as a promising strategy to control abiotic stresses; their synergic effects on controlling drought and Cr toxicity are unknown. This study aimed to investigate the effects of foliar applications of SiO2 (200 mg L-1) and TiO2 (60 mg L-1) NPs on growth, chlorophyll (Chl) content, lipid peroxidation, antioxidant enzyme, and fatty acid profile of black cumin (Nigella sativa L.) under drought (soil moisture at 50% field capacity (FC) and Cr toxicity as K2Cr2O7 at 10 mg L-1. The results showed that drought and Cr stress significantly reduced growth and Chl a + b, but increased malondialdehyde (MDA), electrolyte leakage (EL), and the activity of antioxidant enzymes. The use of NPs particularly SiO2 NPs modulated drought and Cr stress through enhancing Chl content and alleviating MDA, EL, and antioxidant activities. Under drought stress, SiO2 NPs enhanced shoot weight (26%), root weight (25%), seed yield (36%), Chl content (26%), but lowered MDA (22%), EL (14%), catalase (CAT, 32%), and superoxide dismutase (SOD, 33%) activity relative to non-NP application. The main changes in fatty acid profile corresponded to abiotic stresses, where they increased polyunsaturated fatty acids (PUFAs) but decreased monounsaturated fatty acids (MUFAs). Multivariate analysis showed that plant weight, seed yield, Cl content, and oleic acid negatively correlated with MDA, EL, antioxidant enzymes, and linoleic acid. In total, the use of SiO2 is recommended for modulating drought and Cr stress to reach the maximum seed yield of black cumin and a healthy fatty acid profile.

Titanium dioxide nanoparticles induce apoptosis through ROS-Ca2+-p38/AKT/mTOR pathway in TM4 cells.

Titanium dioxide nanoparticles (TiO2 NPs) can cause apoptosis in TM4 cells; however, the underlying mechanism has not been entirely elucidated. The purpose of this study was to investigate the effects of TiO2 NPs on ROS, Ca2+ level, p38/AKT/mTOR pathway, and apoptosis in TM4 cells and to evaluate the role of Ca2+ in p38/AKT/mTOR pathway and apoptosis. After exposure to different concentrations (0, 50, 100, 150, and 200 µg/mL) of TiO2 NPs for 24 h, cell viability, ROS, Ca2+ level, Ca2+-ATPase activity, p38/AKT/mTOR pathway-related proteins, apoptosis rate, and apoptosis-related proteins (Bax, Bcl-2, Caspase 3, Caspase 9, and p53) were detected. The ROS scavenger NAC was used to determine the effect of ROS on Ca2+ level. The Ca2+ chelator BAPTA-AM was used to evaluate the role of Ca2+ in p38/AKT/mTOR pathway and apoptosis. TiO2 NPs significantly inhibited cell viability, increased ROS level, and elevated Ca2+ level while suppressing Ca2+-ATPase activity. TiO2 NPs regulated the p38/AKT/mTOR pathway via increasing p-p38 level and decreasing p-AKT and p-mTOR levels. TiO2 NPs significantly enhanced the apoptosis. NAC attenuated Ca2+ overload and reduction in Ca2+-ATPase activity caused by TiO2 NPs. BAPTA-AM alleviated TiO2 NPs-induced abnormal expression of p38/AKT/mTOR pathway-related proteins. BAPTA-AM assuaged the apoptosis caused by TiO2 NPs. Altogether, this study revealed that TiO2 NPs elevated intracellular Ca2+ level through ROS accumulation. Subsequently, the heightened intracellular Ca2+ level was observed to exert regulation over the p38/AKT/mTOR pathway, ultimately culminating in apoptosis. These results provides a complementary understanding to the mechanism of TiO2 NPs-induced apoptosis in TM4 cells.