Nanoparticle-induced Toxicity Research Articles

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

Expression of concern “Assessment of the neuroprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in rats” [Neurotoxicology 95 (2023) 232-243

Expression of concern “Assessment of the neuroprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in rats” [Neurotoxicology 95 (2023) 232-243

Assessment of the neuroprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in rats

BackgroundWith the recent growth in the applications of silver nanoparticles (Ag-NPs), worries about their harmful effects are increasing. Selenium plays a vital role in the antioxidant defense system as well as free radical scavenging activity. ObjectivesThis study aims to inspect the neuroprotective effect of selenium-loaded chitosan nanoparticles (CS-SeNPs) against the adverse impact of Ag-NPs on brain tissue in adult rats. DesignRats were divided into four groups: group I (control) was administered distilled water (0.5 mL/kg), group II was administered Ag-NPs (100 mg/kg), group III was administered Ag-NPs (100 mg/kg) and CS- SeNPs (0.5 mg/kg) and group IV received only CS- SeNPs (0.5 mg/kg) daily by oral gavage. After 60 days, rats were subjected to behavioral assessment and then euthanized. Brain tissues were obtained for estimation of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2-deoxy Guanosine (8-OHdG), and Nuclear Factor Erythroid 2 Like Protein 2 (Nrf2). Also, histological examination of the brain and immunohistochemical detection of glial fibrillary acidic protein (GFAP) were investigated Resultsexposure to Ag-NPs induced marked neurotoxicity in the brain tissue of rats that was manifested by decreased levels of TAC and Nrf2 with increased levels of MDA and 8-OHdG. Also, various pathological lesions with an increase in the number of GFAP immunoreactive cells were detected. While brain tissue of rats received Ag-NPs plus CS-SeNPs group (III) revealed significantly fewer pathological changes. ConclusionCo-administration of CS-SeNPs significantly ameliorates most of the Ag-NPs-induced brain damage.

Ultrastructural study of the hepatoprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in the female albino rats.

Ultrastructural study of the hepatoprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in the female albino rats.

Protocatechuic acid mitigates CuO nanoparticles-induced toxicity by strengthening the antioxidant defense system and suppressing apoptosis in liver cells

Due to exceptional properties, copper oxide nanoparticles (CuO NPs) are now being applied in diverse fields such as agriculture, cosmetics, food industry, and medicine. There is enough scientific evidence that CuO NPs are toxic to living organisms. However, no effective method is available to mitigate the health hazard of the CuO NPs. This study aimed to investigate the possible cytoprotective mechanism of protocatechuic acid (PCA) from the toxicity of CuO NPs in human liver HepG2 cells and primary rat hepatocytes. CuO NPs were synthesized by a facile hydrothermal method. X-ray diffraction and electron microscopy characterization data confirmed the formation of spherical and crystalline CuO NPs with smooth surface morphology. On the basis of preliminary results, cells are divided into four groups; (i) control group, (ii) PCA group (10 µg/mL, a non-cytotoxic dose), (iii) CuO NPs group (IC50), and (iv) co-exposure group (PCA + CuO NPs). Results show that pre-treatment with PCA significantly abrogates the CuO NPs-induced cytotoxicity and lactate dehydrogenase leakage in both types of cells. CuO NPs-induced reactive oxygen species, hydrogen peroxide, and malondialdehyde levels are remarkably mitigated by the PCA pre-treatment. The depletion in glutathione and several antioxidant enzymes (e.g. glutathione peroxidase, superoxide dismutase, and catalase) because of the CuO NPs exposure is effectively restored by PCA. Caspase-3 gene up-regulation and mitochondrial membrane potential depletion due to CuO NPs exposure are also alleviated by the pre-treatment using PCA. Therefore, this first study reports the mitigating potential of PCA against CuO NPs toxicity in liver cells by restoring the antioxidant defense system and quashing the apoptosis.

Surface-functionalized polystyrene nanoparticles alter transmembrane potential via ion-selective pores maintaining global bilayer integrity.

Although nanoplastics have well-known toxic effects towards the environment and living organisms, their molecular toxicity mechanisms, including the nature of nanoparticle-cell membrane interactions, are still under investigation. We employ dynamic light scattering (DLS), quartz crystal microbalance with dissipation monitoring (QCM-D) and electrophysiology to investigate the interaction between polystyrene nanoparticles (PS NPs) and phospholipid membranes. Our results show that PS NPs adsorb onto lipid bilayers creating soft inhomogeneous films that include disordered defects. PS NPs form an integral part of the generated channels so that the surface functionalization and charge of the NP determine the pore conductive properties. The large difference in size between nanoparticle diameter and lipid bilayer thickness (∼60 nm vs ∼5 nm) suggests a particular and complex lipid-NP assembly that is able to maintain overall membrane integrity. In view of that, we suggest that nanoparticle-induced toxicity in cells could operate in more subtle ways than membrane disintegration, such as inducing lipid reorganization and transmembrane ionic fluxes that disrupt the membrane potential.

Melatonin-mediated resistance to copper oxide nanoparticles-induced toxicity by regulating the photosynthetic apparatus, cellular damages and antioxidant defense system in maize seedlings

The pollution of nanoparticles (NPs) has linked with severe negative effects on crop productivity. Thus, effective strategies are needed to mitigate the phytotoxicity of NPs. The aim of present study was to evaluate the efficacy of exogenously applied melatonin (MT) in mitigating the toxic effects of copper oxide nanoparticles (CuO NPs) from maize seedlings. Therefore, we comprehensively investigated the inhibitory effects of MT against CuO NPs-induced toxicity on morpho-physiological, biochemical and ultrastructural levels in maize. Our results show that CuO NPs (300 mg L−1) exposure displayed significantly reduction in all plant growth traits and induced toxicity in maize. Furthermore, 50 μM MT provided maximum plant tolerance against CuO NPs-induced phytotoxicity. It was noticed that MT improved plant growth, biomass, photochemical efficiency (Fv/Fm), chlorophyll contents (Chl a and Chl b), SPAD values and gas exchange attributes (stomatal conductance, net photosynthetic rate, intercellular CO2 concentration and transpiration rate) under CuO NPs stress. In addition, MT enhanced the antioxidant defense system and conferred protection to ultrastructural (mainly chloroplast, thylakoids membrane and plastoglobuli) damages and stomatal closure in maize plants subjected to CuO NPs stress. Together, it can be stated that the exogenous supply of MT improves the resilience of maize plants against the CuO NPs-induced phytotoxicity. Our current findings can be useful for the enhancement of plant growth and yield attributes in CuO NPs-contaminated soils. The reported information can provide insight into the MT pathways that can be used to improve crop stress tolerance in a challenging environment.

Ethylene accelerates copper oxide nanoparticle-induced toxicity at physiological, biochemical, and ultrastructural levels in rice seedlings.

The enormous use of metal-based nanoparticles (NPs) in different sectors may result in enhanced accumulation in agricultural soil, which could impose negative effects on crop productivity. Hence, strategies are needed to explore the mechanisms of copper oxide nanoparticle (CuO NP)-induced toxicity in crops. The present study aimed to investigate the involvement of ethylene in CuO NP-induced toxicity in rice seedlings. Here, our results indicate that 450mg L-1 of CuO NPs induced toxic effects in rice seedlings. Thus, it was evidenced by the reduced plant biomass accumulation, enhanced oxidative stress indicators, and cellular ultrastructural damages. More importantly, the exogenous supply of ethylene biosynthesis and signaling antagonists cobalt (Co) and silver (Ag) respectively provided tolerance and improved the defense system of rice seedlings against CuO NP toxicity. The ethylene antagonists could significantly reduce the extent of ultrastructural and stomatal damage by controlling the ROS accumulation in rice seedlings under CuO NP stress. Furthermore, Co and Ag augmented the antioxidant defense system against CuO NP-induced toxicity. Contrary to that, all oxidative damage attributes were further enhanced exogenous application of ethylene biosynthesis precursor [1-aminocyclopropane-1-carboxylic acid (ACC)] in the presence of CuO NPs. In addition, ACC could increase the CuO NP-induced stomatal and ultrastructural damages by reducing the ROS-scavenging ability in rice seedlings. Taken together, these results indicate the involvement of ethylene in CuO NP-induced toxicity in rice seedlings.

Gut microbiome and plasma metabolome changes in rats after oral gavage of nanoparticles: sensitive indicators of possible adverse health effects

BackgroundThe oral uptake of nanoparticles is an important route of human exposure and requires solid models for hazard assessment. While the systemic availability is generally low, ingestion may not only affect gastrointestinal tissues but also intestinal microbes. The gut microbiota contributes essentially to human health, whereas gut microbial dysbiosis is known to promote several intestinal and extra-intestinal diseases. Gut microbiota-derived metabolites, which are found in the blood stream, serve as key molecular mediators of host metabolism and immunity.ResultsGut microbiota and the plasma metabolome were analyzed in male Wistar rats receiving either SiO2 (1000 mg/kg body weight/day) or Ag nanoparticles (100 mg/kg body weight/day) during a 28-day oral gavage study. Comprehensive clinical, histopathological and hematological examinations showed no signs of nanoparticle-induced toxicity. In contrast, the gut microbiota was affected by both nanoparticles, with significant alterations at all analyzed taxonomical levels. Treatments with each of the nanoparticles led to an increased abundance of Prevotellaceae, a family with gut species known to be correlated with intestinal inflammation. Only in Ag nanoparticle-exposed animals, Akkermansia, a genus known for its protective impact on the intestinal barrier was depleted to hardly detectable levels. In SiO2 nanoparticles-treated animals, several genera were significantly reduced, including probiotics such as Enterococcus. From the analysis of 231 plasma metabolites, we found 18 metabolites to be significantly altered in Ag-or SiO2 nanoparticles-treated rats. For most of these metabolites, an association with gut microbiota has been reported previously. Strikingly, both nanoparticle-treatments led to a significant reduction of gut microbiota-derived indole-3-acetic acid in plasma. This ligand of the arylhydrocarbon receptor is critical for regulating immunity, stem cell maintenance, cellular differentiation and xenobiotic-metabolizing enzymes.ConclusionsThe combined profiling of intestinal microbiome and plasma metabolome may serve as an early and sensitive indicator of gut microbiome changes induced by orally administered nanoparticles; this will help to recognize potential adverse effects of these changes to the host.

Lysosomal cysteine proteases are mediators of cell death in macrophages following exposure to amorphous silica nanoparticles

Increasing use of nanomaterials in everyday products such as cosmetics, medicines and food packaging is of grave concern given the lack of understanding with regards the impact such materials have on biological systems. The aim of this study is to examine cell death induced by cationic amorphous silica nanoparticles and determine the involvement of lysosomal cysteine proteases in this process. We report that multiple forms of cell death including apoptosis and pyroptosis are elicited following exposure to amorphous silica nanoparticles and that lysosomal cysteine proteases are involved in both cell death pathways in macrophages. Interestingly, lysosomal cysteine protease mRNA expression and release into the extracellular environment is induced following exposure to amorphous silica nanoparticles. Previously, the determination of nanoparticle-induced toxicity has focused on cytokine readouts, but the work presented here demonstrates that changes to normal protease biology should also be considered when evaluating the molecular mechanisms by which nanoparticulate matter causes cellular inflammation and death.

Modulatory Role of Quercetin in Mitochondrial Dysfunction in Titanium Dioxide Nanoparticle-Induced Hepatotoxicity.

Background: Titanium dioxide (TiO2) nanoparticles are among the largely manmade nanomaterials worldwide and are broadly used as both industrial and user products. The primary target site for several nanoparticles is the liver, including TiO2 nanoparticles (TNPs), exposed directly or indirectly through ingestion of contaminated water, food, or animals and elevated environmental contamination. Oxidative stress is a known facet of nanoparticle-induced toxicity, including TNPs. Mitochondria are potential targets for nanoparticles in several types of toxicity, such as hepatotoxicity. Nevertheless, its causal mechanism is still controversial due to scarcity of literature linking the role of mitochondria-mediated TNP-induced hepatotoxicity. Aim: The objective of the current study was to evaluate the relation of mitochondrial oxidative stress and respiratory chain mechanisms with TNP-induced mitochondrial dysfunction in vitro, and explore the hepatoprotective effect of quercetin (QR), which is a polyphenolic flavonoid abundant in fruits and vegetables with known antioxidant properties, on TNP-induced mitochondrial oxidative stress and disturbance in respiratory chain complex enzymes in the liver of rats. Results: Enzymatic and non-enzymatic antioxidant levels, oxidative stress markers, and mitochondrial complexes were assessed with regard to TNP-induced hepatotoxicity. The depleted lipid peroxidation levels and protein carbonyl content, in mitochondria, induced by TNPs were restored significantly by pretreatment with QR. QR modulated the altered non-enzymatic and enzymatic antioxidants and mitochondrial complex enzymes. Conclusion: Based on the findings, we conclude that QR, which mitigates oxidative stress caused by mitochondrial dysfunction, holds promising capability to potentially diminish TNP-induced adverse effects in the liver.

Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo

BackgroundSilver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations.ResultsThe consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation.ConclusionsOur integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

Nitric oxide overcomes copper and copper oxide nanoparticle-induced toxicity in Sorghum vulgare seedlings through regulation of ROS and proline metabolism.

This study aimed to investigate the phytotoxic effect of copper (Cu) and copper nanoparticles (CuONPs) and ameliorative potential of nitric oxide (NO) against these toxic materials in Sorghum vulgare Pers. seedlings. Data suggested that exposure of Cu and CuONPs significantly reduced growth, chlorophyll, carotenoids and protein in root and shoot, which coincided with increased Cu accumulation. However, addition of sodium nitroprusside (SNP, a donor of NO) lowered Cu and CuONPs mediated toxicity through restricting Cu accumulation and improving photosynthetic pigments and total soluble protein contents. Data further suggested that exposure of Cu and CuONPs significantly increased hydrogen peroxide (H2 O2 ), superoxide radicals (O2 •- ), and malondialdehyde (MDA) contents. Enhanced level of oxidative stress severely inhibited the enzymatic activities of glutathione reductase (GR), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) but enhanced superoxide dismutase (SOD) and catalase (CAT) activity. However, addition of SNP positively regulated antioxidants enzymes activity, particularly the enzymes involved in the ascorbate-glutathione cycle to overcome Cu- and CuONPs-induced stress in Sorghum seedlings. Further, Cu and CuONPs enhanced accumulation of free proline through inducing Δ1 -pyrroline-5-carboxylate synthetase (P5CS) activity while lowering the proline dehydrogenase (PDH) activity. However, addition of SNP reversed these responses. Therefore, overall results revealed that SNP has enough potential of reducing the toxicity of Cu and CuONPs in Sorghum seedlings through regulation of proline metabolism and activity of enzymes of the ascorbate-glutathione cycle. These findings can be employed in developing new resistant varieties of Sorghum having enhanced tolerance against Cu or CuONP stress and improved productivity.

The Effects of Oral Silver Nanoparticles and Propolis on the Level of Lipid Peroxidation in Male Wistar Rats

Background: Oxidative stress is a leading factor in developing silver nanoparticle-induced toxicity. Objective: This study evaluated the effects of oral prescription of different doses of silver nanoparticles and propolis on lipid peroxidation in male Wistar rats. Methods: The male Wistar rats were randomly divided into four groups. Control group and three different treatment groups with oral prescription of 30 ppm, 60 ppm, and 60 ppm of silver nanoparticles with 200 mg/kg of propolis. The serum level of Malondialdehyde (MDA) was measured by Thiobarbituric Acid Reactive Substances (TBARS) assay using Thiobarbituric Acid (TBA). Results: The serum level of MDA as a marker of lipid peroxidation in the control group was 1.92 mM/mL, and in other groups that received silver nanoparticles (30 ppm, 60 ppm, 60 ppm with 200 mg/kg propolis) were respectively 2.82, 3.83 and 2.62 mM/mL. MDA level also increased at the doses of 30 ppm and 60 ppm compared to the control group and decreased when propolis was prescribed with silver nanoparticles in the third group; however, its value did not reach the level of the control group. Minimal levels of serum lipid peroxidation were observed when silver and propolis nanoparticles were administered to male rats. Conclusion: The mixture of silver nanoparticles and propolis reduces the toxic effects of silver nanoparticles; it preserves and increases the efficiency of this compound in medical applications.

Autophagy deficiency exacerbates acute lung injury induced by copper oxide nanoparticles

Copper oxide nanoparticles (CuONPs) are one of the widely used metal nanoparticles in the industrial and commercial fields. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome and has been linked to nanoparticles-induced toxicity. In particular, the roles of autophagy in response to CuONPs have been explored in vitro, although the conclusions are controversial. To clarify the role of autophagy in CuONPs-induced acute lung injury, microtubule-associated protein 1 light chain 3 beta (Map1lc3b or lc3b) knockout mice and their corresponding wild type mice are applied. Our results showed that single-dose intratracheal instillation of CuONPs with dosages of 1.25, 2.5 or 5 mg/kg caused acute lung injury 3 days after treatment in a dose-dependent manner, as evidenced by deteriorative lung histopathology, more infiltration of macrophage cells, increased oxidative stress and copper ions. Loss of lc3b resulted in aggravated lung injury induced by CuONPs, which was probably due to the blockade of mitophagy and consequently the accumulation of aberrant mitochondria with overloaded copper ions. Our study provides the first in vivo evidence that autophagy deficiency exacerbates CuONPs-induced acute lung injury, and highlights that targeting autophagy is a meaningful strategy against CuONPs-associated respiratory toxicity.

Neuroprotective effect of sesamol against aluminum nanoparticle-induced toxicity in rats.

Alumina nanoparticles (ALNPs) are widely used causing neurobehavioral impairment in intoxicated animals and humans. Sesamol (SML) emerged as a natural phytochemical with potent antioxidant and anti-inflammatory properties. However, no study has directly tested the potential of SML to protect against AlNP-induced detrimental effects on the brain. AlNPs (100 mg/kg) were orally administered to rats by gavage with or without oral sesamol (100 mg/kg) for 28 days. In AlNP-intoxicated group, the brain AChE activity was elevated. The concentrations of MDA and 8-OHdG were increased suggesting lipid peroxidation and oxidative DNA damage. GSH depletion with inhibited activities of CAT and SOD were demonstrated. Serum levels of IL-1β and IL-6 were elevated. The expressions of GST, TNF-α, and caspase-3 genes in the brain were upregulated. Histopathologically, AlNPs induced hemorrhages, edema, neuronal necrosis, and/or apoptosis in medulla oblongata. The cerebellum showed loss of Purkinje cells, and the cerebrum showed perivascular edema, neuronal degeneration, necrosis, and neuronal apoptosis. However, concomitant administration of SML with AlNPs significantly ameliorated the toxic effects on the brain, reflecting antioxidant, anti-inflammatory, and anti-apoptotic effects of SML. Considering these results, sesamol could be a promising phytochemical with neuroprotective activity against AlNP-induced neurotoxicity.

Dietary supplementation with melatonin: influence on growth performance, oxidative stress status, and amelioration of silver nanoparticles-induced toxicity in Nile tilapia (Oreochromis niloticus).

Excessive use of silver nanoparticles (AgNPs) due to antibacterial properties can raise concerns about their release into environment and potential toxicity in aquatic organisms. Melatonin has several physiological functions especially antioxidant potential against oxidative stress. The current study was conducted to investigate the potential effects of two doses of dietary melatonin on growth performance, plasma biochemistry, and liver enzyme activity in Nile tilapia (Oreochromis niloticus) juveniles. We also investigated the potential ameliorative effect of melatonin in AgNPs-induced biochemical alterations in tilapia fish. The results showed that melatonin-supplemented diets had no significant effect on growth performance of fish (P>0.05). The liver GPx activity increased in fish fed melatonin-supplemented diets (P<0.05), but the SOD activity showed no significant difference in comparison with the control (P>0.05). The administration of melatonin-supplemented diets reduced the activity of liver MDA compared to the control (P<0.05). Feeding fish with high melatonin-supplemented diet (200 mg kg-1 of diet) decreased the plasma glucose, total protein, and AST levels (P<0.05). The liver GPx and SOD activities were higher in high melatonin-treated fish exposed to AgNPs than the control group (P<0.05). Dietary melatonin decreased the liver MDA activity in AgNPs-exposed fish. The plasma glucose, AST, and ALT levels in melatonin-treated fish exposed to AgNPs decreased compared to the untreated exposed fish (P<0.05). Melatonin-treated fish exposed to 0.05 and 0.5 mg L-1 of AgNPs had lower plasma LDH level than the control group (P<0.05). The results showed that consumption of melatonin-supplemented diets could modulate some of the biochemical indices of plasma and liver in Nile tilapia. The findings also indicated the ameliorative effect of dietary melatonin on AgNPs-induced toxicity in Nile tilapia.

The role of exogenous silicon to mitigate Al2O3 nanoparticle-induced toxicity in barley (Hordeum vulgare L.)

In this study, we used silicon (Si, in the form of K2SiO3, 2 mM) to alleviate the toxicity of aluminum oxide (Al2O3) nanoparticles (NPs) in barley (Hordeum vulgare L.). Using Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) analyses, we showed that the Al2O3 NPs were taken up by barley plants. Barley growth was negatively affected by the addition of 3 g l-1 nano-Al2O3, whereas the diminishing effect of NPs on barley growth was not obvious when 1 g l-1 nano-Al2O3 was applied, indicating that the nano-Al2O3 action is dependent on nano-Al2O3 dose. Si pretreatment ameliorated toxic effects of high nano-Al2O3 on root growth. Si pretreatment did not decrease nano-Al2O3 entry into roots but reduced nano-Al2O3 accumulation in the shoot. The restriction of the root-to-shoot translocation of nano-Al2O3 was one of the important mechanisms for Si to mitigate high nano-Al2O3 toxicity. The occurrence of oxidative stress was found under 3 g l1 nano-Al2O3 treatment, as evaluated by the accumulation of malondialdehyde (MDA). Exogenous addition of Si could alleviate toxicity symptoms induced by Al2O3 nanoparticles by reducing lipid peroxidation via enhancing antioxidant activity of catalase as well as by limiting the root-to-shoot translocation of nano-Al2O3. These data provide the first direct evidence that the Si pretreatment ameliorates nano Al2O3 phytotoxicity in plants.

Multiparametric nanoparticle-induced toxicity readouts with single cell resolution in HepG2 multicellular tumour spheroids.

The use of nanomaterials as therapeutic delivery vehicles requires their careful pre-clinical evaluation. Of particular importance in this regard is measurement of cellular toxicity, ideally assessing multiple parameters in parallel from various relevant subcellular organelles. In recent years it has become evident that in vitro monolayer-grown cells do not always accurately predict any toxicity response seen in vivo, and so there is a need for more sophisticated in vitro cell models, employing a greater depth of characterisation. In this work we present an automated high-content screening microscopy approach for quantifying nanoparticle-induced toxicity in a three-dimensional multicellular tumour spheroid (MCTS) cell model. As a proof-of-principle, we perform a comparative toxicity profile study of carboxylate- versus amine-modified polystyrene nanoparticles in HepG2 spheroids. Following treatment with these nanoparticle types, we demonstrate that several hundred spheroids, of various sizes, can be morphologically profiled in a single well using automated high-content image analysis. This provides a first level of information about spheroid health in response to nanoparticle treatment. Using a range of fluorescent reporters assessing membrane permeability, lysosome function and mitochondrial activity, we also show that nanoparticle-induced toxicity information can be obtained from individual cells with subcellular resolution. Strikingly, our work demonstrates that individual cells do not all behave in a consistent manner within a spheroid structure after exposure to nanoparticles. This highlights the need for toxicity studies to not only assess an appropriate number of spheroids, but also the importance of extracting information at the subcellular level.

Involvement of glucosinolates in the resistance to zinc oxide nanoparticle-induced toxicity and growth inhibition in Arabidopsis.

Zinc oxide nanoparticles (ZnO NPs) are widely used to manufacture textile fibers, synthetic rubber, and paint. However, crop yields and quality are threatened by the increased use of metallic NPs in industry, which has resulted in their accumulation in agricultural land. Many studies have shown that plants defend against biotic and abiotic stresses through the activities of metabolites and hormones. However, whether glucosinolates (GSs) are involved in plant responses to ZnO NP-related stress remains unknown. In this study, wild-type (WT) and GS mutant (myb28/29 and cyp79B2/B3) Arabidopsis plants were subjected to ZnO NP stress to address this question. Our results showed that exposure to ZnO NPs promoted GS accumulation and induced the relative messenger RNA (mRNA) expression levels of GS biosynthesis-related genes. Moreover, ZnO NP treatment adversely affected root length, the number of lateral roots, chlorophyll contents, and plant biomass. Importantly, our results showed that root growth, chlorophyll contents, and plant biomass were all decreased in the GS mutants compared with those in WT plants. Overall, our results showed that WT plants tolerated ZnO NP-induced stress more efficiently than the GS mutants, suggesting that GSs are involved in plant resistance to ZnO NP-induced toxicity.