Toxicity Of ZnO NPs Research Articles

Toxic effects of ZnO NPs on immune response and tissue pathology in Mytilus galloprovincialis

Nano-zinc oxide (ZnO NPs), as widely used nanomaterials, are inevitably released into aquatic environments, posing potential threats to aquatic organisms. Mytilus galloprovincialis is a bivalve species sensitive to changes in marine ecological environments, but there has been limited research on its toxicity response to ZnO NPs. Therefore, we selected M. galloprovincialis as the research subject and exposed them to 50 µg/L ZnO NPs for 96 h and 30 days to determine the dissolution of ZnO NPs in seawater and their distribution in M. galloprovincialis. The toxicity of ZnO NPs in M. galloprovincialis was then evaluated through gene expression, tissue pathology, and cellular immune response. The results showed that ZnO NPs could enrich Zn in various tissues of the mussel, in the order of gills > hepatopancreas > adductor muscle > mantle. Seven immune-related genes including four heat shock protein genes (HSPA12A, sHSP24.1, sHSP22, TCTP) and three apoptotic genes (Ras, p63 and Bcl-2) were altered to varying degrees. There was a downward trend in lysosomal membrane stability of M. galloprovincialis after exposure to ZnO NPs for 96 h and 30 days, while ROS and apoptosis rates increased significantly. Furthermore, the seven genes, apoptosis, LMS, and ROS were dependent on exposure time, treatment, and their interaction. Histopathological damage included disorganisation of hepatopancreas epithelial cells, gill filament swelling, and contraction of blood sinuses. These results indicated that ZnO NPs exerted toxicity in M. galloprovincialis, affecting the immune system, resulting in changes in the expression of immune-related genes and ultimately leading to histopathological changes. Our research findings could contribute to systematically understand the impact of ZnO NPs on bivalves in aquatic environments and provide a theoretical basis for marine pollution assessment.

Toxicity of zinc oxide nanoparticles: Cellular and behavioural effects

Due to their extensive use, the release of zinc oxide nanoparticles (ZnO NP) into the environment is increasing and may lead to unintended risk to both human health and ecosystems. Access of ZnO NP to the brain has been demonstrated, so their potential toxicity on the nervous system is a matter of particular concern. Although evaluation of ZnO NP toxicity has been reported in several previous studies, the specific effects on the nervous system are not completely understood and, particularly, effects on genetic material and on organism behaviour are poorly addressed. We evaluated the potential toxic effects of ZnO NP in vitro and in vivo, and the role of zinc ions (Zn2+) in these effects. In vitro, the ability of ZnO NP to be internalized by A172 glial cells was verified, and the cytotoxic and genotoxic effects of ZnO NP or the released Zn2+ ions were addressed by means of vital dye exclusion and comet assay, respectively. In vivo, behavioural alterations were evaluated in zebrafish embryos using a total locomotion assay. ZnO NP induced decreases in viability of A172 cells after 24 h of exposure and genetic damage after 3 and 24 h. The involvement of the Zn2+ ions released from the NP in genotoxicity was confirmed. ZnO NP exposure also resulted in decreased locomotor activity of zebrafish embryos, with a clear role of released Zn2+ ions in this effect. These findings support the toxic potential of ZnO NP showing, for the first time, genetic effects on glial cells and proving the intervention of Zn2+ ions.

The Effect of ZnO Nanoparticles Functionalized with Glutamine and Conjugated with Thiosemicarbazide on Triggering of Apoptosis in the Adenocarcinoma Gastric Cell Line.

Gastric carcinoma is the fourth most common malignancy worldwide. Conjugation of metal nanoparticles with thiosemicarbazones has shown considerable anti-cancer potential. Zinc oxide nanoparticles (ZnO NPs) were synthesized, functionalized by glutamine, and conjugated with thiosemicarbazide (ZnO@Gln-TSC). Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy imaging, energy-dispersive X-ray, DLS, and zeta potential were used to characterize the NPs. The toxicity of ZnO NPs, TSC, ZnO@Gln-TSC NPs, and oxaliplatin in AGS cells and ZnO NPs and ZnO@Gln-TSC NPs in HEK293 cells was investigated by MTT assay. Cell apoptosis was evaluated by flow cytometry, caspase-3 activity, and Hoechst staining assays. The intra-cellular reactive oxygen species level and expression level of the CASP3 gene in AGS cells treated with ZnO@Gln-TSC NPs were evaluated. The NPs were in the size range of 20 to 70 nm. The DLS and zeta potential were 374 nm and -31.7 mV, respectively. In MTT, the IC50 of ZnO, TSC, oxaliplatin, and ZnO@Gln-TSC NPs for AGS cells were 130, 80.5, 67.7, and 9.8 μg/mL, respectively, and the IC50 of ZnO and ZnO@Gln-TSC NPs for HEK293 cells were 215 and 150.5 μg/mL, respectively. Flow cytometry showed higher apoptosis in the cell treated with the NPs and TSC. Apoptotic features, including cell shrinkage, were recognized. A significant increase of 5.9 folds in the level of ROS was noticed. The activity of caspase-3 and the expression level of the CASP3 gene were increased by1.83 and 1.6 folds after exposure to ZnO@Gln-TSC NPs, respectively. This study revealed the anti-cancer potential of ZnO@Gln-TSC NPs to be used for gastric cancer treatment after further in vitro and in vivo assays.

Maternal exposure to zinc oxide nanoparticles causes cochlear dysfunction in the offspring.

Introduction: Zinc oxide nanoparticles (ZnO NPs) have been engineered and are largely used in material science and industry. This large and increasing use justifies a careful study about the toxicity of this material for human subjects. The concerns regard also the reproductive toxicity and the fetotoxicity. Materials and methods: The effect of the exposure to ZnO NPs on the cochlear function was studied in a group of pregnant CD1 mice and in their offspring. This study is part of a larger toxicological study about the toxicity of ZnO NPs during pregnancy. Four groups were analyzed and compared, exposed and non-exposed dams and their offspring. The cochlear function was quantitatively assessed by means of Distortion Product Otoacoustic Emissions (DPOAEs). Results and discussion: A large statistically significant difference was found between the non-exposed dams offspring and the exposed dams offspring (p = 1.6 · 10-3), whose DPOAE levels were significantly lower than those of non-exposed dams offspring and comparable to those of the adults. The DPOAE levels of the exposed and non-exposed dams were very low and not significantly different. This occurrence is related to the fact that these mice encounter a rapid aging process. Conclusion: Our findings show that maternal exposure to ZnO NPs does not reflect in overt toxicity on fetal development nor impair offspring birth, however it may damage the nervous tissue of the inner ear in the offspring. Other studies should confirm this result and identify the mechanisms through which ZnO NPs may affect ear development.

Antioxidant response to ZnO nanoparticles in juvenile Takifugu obscurus: protective effects of salinity.

The extensive utilization of Zinc Oxide nanoparticles (ZnO NPs) has garnered significant attention due to their detrimental impacts on ecosystem. Unfortunately, ecotoxicity of ZnO NPs in coastal waters with fluctuating salinity has been disregarded. This study mainly discussed the toxic effects of ZnO NPs on species inhabiting the transition zones between freshwater and brackish water, who are of great ecological and economic importance among fish. To serve as the model organism, Takifugu obscurus, a juvenile euryhaline fish, was exposed to different ZnO NPs concentrations (0-200 mg/L) and salinity levels (0 and 15 ppt). The results showed that a moderate increase in salinity (15 ppt) could alleviate the toxic effect of ZnO NPs, as evidenced by improved survival rates. The integrated biomarker response index on oxidative stress also revealed that the toxicity of ZnO NPs was higher in freshwater compared to brackish water. These outcomes can be attributed to higher salinity (15 ppt) reducing the bioavailability of ZnO NPs by facilitating their aggregation and inhibiting the release of metal ions. It is noteworthy that elevated salinity was found to alleviate ZnO NPs toxicity by means of osmotic adjustment via the activation of Na+/K+-ATPase activity. This study demonstrates the salinity-dependent effect of ZnO NPs on T. obscurus, suggesting the possibility for euryhaline fish like T. obscurus to adapt their habitat towards more saline environments, under constant exposure to ZnO NPs.

ZnO nanoparticles impair autophagic flux and cell viability through the TRIM16-NRF2-p62 pathway in inflammatory keratinocytes

PurposeZinc oxide nanoparticles (ZnO NPs) are widely used in sunscreen, cosmetics, and topical drugs. Most previous studies have confirmed the safety of ZnO NPs applied to normal skin; however, little is known about the safety and potential toxicity of ZnO NPs applied to inflamed skin. This study aimed to evaluate the exposure risk of ZnO NPs in the treatment of inflammatory skin diseases. MethodsNormal human and tumor necrosis factor-α (TNF-α)-induced inflammatory keratinocytes were incubated with ZnO NPs to assess their toxic effects on cell viability and autophagy signaling pathway. Tandem mass tag (TMT)-based proteomics analysis was used to identify differentially expressed proteins following incubation of inflammatory keratinocytes with ZnO NPs. Protein expression was assessed by Western blot, and double fluorescent labeling and siRNA-knockdown further elucidated the role of the TRIM16-NRF2-p62 pathway in mediating the effects of ZnO NP. ResultsIn TNF-α-induced inflammatory keratinocytes, ZnO NPs activated cytoprotective autophagy and mediated p62-related autophagic flux block, thereby reducing the viability of inflammatory keratinocytes. Additionally, TRIM16-NRF2 was essential in ZnO NP-mediated autophagy flux block and cell viability reduction in inflammatory keratinocytes. Inhibition of the TRIM16-NRF2 pathway reduced p62 levels, alleviated autophagy flux blockade, and slightly restored the viability of inflammatory keratinocytes. ConclusionZnO NPs activated protective cell autophagy. Blockade of autophagy flux mediated by the TRIM16-NRF2-p62 pathway led to decreased cell viability. This study provided a deeper understanding of the toxicity mechanism of ZnO NPs in inflammatory keratinocytes.

Combined impact of elevated temperature and zinc oxide nanoparticles on physiological stress and recovery responses of Scylla serrata

Global climate change is the major cause behind unexpected fluctuations in temperature. In recent years, application of nanotechnology also has become widespread and nanomaterials are constantly being released into aquatic environments, posing a potential risk to various organisms and ecosystems. The lack of detailed understanding of how multiple stressors work, and how they differ from single stressors, impede to assess their combined effect on aquatic organisms and ecosystems. The prime aim of the current investigation is to decipher the toxicity of ZnO-NP after simultaneous exposure to a global environmental stressor, elevated temperature for 14 days, followed by a 7 days recovery period, on the eco-physiological responses of mud crab Scylla serrata collected from Sundarbans. Physiological energetics such as ingestion, assimilation, absorption, respiration, and excretion rates were measured to determine the Scope for growth (SfG). Additionally, we assessed various biomarkers from different levels of biological organisation (antioxidant, detoxification defence mechanisms, and lipid peroxidation levels) of the species. Combined stress attenuated the SfG in crabs which deteriorated further in the recovery phase. Oxidative stress also exacerbated under coalesced stress condition. Recovery was not observed in crabs with increased lipid peroxidation level under combined stress conditions. Elevated temperature disturbed the energy budget of crabs as mirrored by diminished energy left for compensatory actions under added metal stress, ultimately sensitizing the animals to ZnO NP pollutants. The current results advocate future ocean temperature to aggravate the impact of metal NP pollution and induce oxidative damage in S. serrata.

Zinc oxide nanoparticles disrupt development and function of the olfactory sensory system impairing olfaction-mediated behaviour in zebrafish

Zinc (Zn) is an essential metal present in numerous enzymes throughout the body, playing a vital role in animal and human health. However, the increasing use of zinc oxide nanomaterials (ZnONPs) in a diverse range of products has raised concerns regarding their potential impacts on health and the environment. Despite these concerns, the toxicity of ZnONP exposure on animal health remain poorly understood. To help address this knowledge gap, we have developed a highly sensitive oxidative stress (OS) biosensor zebrafish capable of detecting cell/tissue-specific OS responses to low doses of various oxidative stressors, including Zn, in a live fish embryo.Using live-imaging analysis with this biosensor zebrafish embryo, we discovered that the olfactory sensory neurons in the brain are especially sensitive to ZnOP exposure. Furthermore, through studies monitoring neutrophil migration and neuronal activation in the embryonic brain and via behaviour analysis, we have found that sub-lethal doses of ZnONPs (ranging from 0.033 to 1 mg/L nominal concentrations), which had no visible effect on embryo growth or morphology, cause significant localised inflammation, disrupting the neurophysiology of olfactory brain tissues and ultimately impaired olfaction-mediated behaviour. Collectively, these findings establish a potent and important effect mechanism for ZnONP toxicity, indicating the olfactory sensory system as the primary target for ZnONPs as an environmental toxicant in aquatic environments. Our result also highlights that even low doses of ZnONPs can have detrimental effects on the olfactory sensory system, surpassing previous expectations. The importance of olfaction in environment sensing, sex behaviours and overall fitness across species raises concerns about the potential impact of ZnONPs on olfaction-mediated brain function and behaviour in animals and humans. Our study emphasises the need for greater consideration of the potential risks associated with these nanomaterials.

Nano zinc oxide induced lipid peroxidation, oxidative stress, genotoxicity, phagocytic alteration, and detoxification response in the coelomocytes of an anecic earthworm of India

Zinc oxide nanoparticle (ZnO NP) is an emerging soil pollutant of industrial origin. The unique physicochemical properties of ZnO NP viz. the bioavailability and subsequent ecotoxicological effects on organisms have made it an ecological concern. Lampito mauritii (Kinberg, 1866) is a common anecic earthworm and is considered as a keystone species of soil ecosystems in India. They are continuously exposed to various environmental toxins during their feeding and other activities. The current study aimed to estimate the immunotoxicological effects of ZnO NP in the coelomocytes, the chief immunoeffector cells of L. mauritii. The results of the study indicated decreased total count, phagocytic activity, antioxidative, and detoxifying potential of the coelomocytes in L. mauritii at 7 and 14 days of exposure. ZnO NP exposure resulted in the generation of oxidative molecules, lipid peroxidation, and DNA damage within coelomocytes. The higher degree of cytotoxicity on ZnO NP exposure was suggestive of immunocompromisation in L. mauritii. An integrated biomarker response (IBR) guided methodology was also utilized in estimating the comprehensive effects of ZnO NP on the health of L. mauritii. The present study would provide useful information on the ZnO NP induced chemical stress in L. mauritii, with the selected endpoints having the potential to function as markers for ZnO NP toxicity.

The toxicity and uptake of bulk and nano-sized ZnO particles in wheat (Triticum aestivum) seedlings

The effect of synthesized nano-sized ZnO particles (ZnO NPs) on wheat germination and growth parameters (Triticum aestivum L.) was studied compared to bulk Zn. Results showed that adding bulk Zn resulted in no significant differences in germination parameters compared to the control samples. On the other hand, the addition of ZnO NPs showed significant differences (p < 0.05) in all germination parameters in comparison to the blank (control) samples. Moreover, the general average Zn concentrations in the plant were 141 and 253 mg kg−1 (dry weight) for bulk Zn and ZnO NPs treated plants, respectively, indicating preferential uptake of ZnO NPs. The addition of c. 10 mg L−1 of ZnO NPs to the wheat shoot system promoted chlorophyll formation equal to 100 mg L−1 addition of bulk Zn. Adding bulk Zn and ZnO NPs reduced root growth substantially compared to the control samples. The effective toxic dose (so-called EC50) for ZnO NPs and bulk Zn was 20.7 and 522 mg Zn L−1, respectively, indicating much higher toxicity of ZnO NPs and highlighting the nano-specific toxicity of nano-sized Zn. The wheat uptake of ZnO NPs was well fitted to a nonlinear Freundlich-like expression, suggesting that our model could effectively predict mass production fertilization procedures. The present study may thus help to increase Zn biofortification in cereals by using ZnO NPs, which may in turn be very helpful for populations suffer from Zn malnutrition.

Effects of dietary zinc oxide nanoparticles supplementation on broiler growth performance, zinc retention, liver health status, and gastrointestinal microbial load

BackgroundZinc (Zn) is an essential trace element for poultry health and biological functions. Inorganic Zn, like Zn oxide and Zn sulfate, was commonly used in poultry feed due to its low cost. However, the bioavailability of inorganic Zn is low, leading to a high level of Zn being added to the feed and resulting in other issues. Zinc oxide nanoparticles (ZnO NPs) have emerged as a promising alternative to their bulkier counterparts, but concerns about their safety persist. Therefore, this study aimed to evaluate the potential benefits and toxicity of dietary ZnO NPs as a feed supplement and antibacterial agent in broiler chickens. Methods180 broiler chicks (Cobb500) were randomly allocated to five dietary treatment groups (36 birds/group). The experimental treatment groups were as follows: (G1) basal diet supplemented with 100 mg kg−1 ZnO (control group), (G2-G5) basal diet supplemented with 10, 40, 70, and 100 mg kg−1 ZnO NPs. The effects of dietary ZnO NPs at different inclusion levels were studied by measuring growth performance (FI, BWG, and FCR), Zn retention, liver enzyme activity, lymphoid organ weight, and gastrointestinal microbial load. ResultsThe results showed that dietary ZnO and different levels of ZnO NPs inclusion had no effect on broiler growth performance (p > 0.05). The birds fed dietary ZnO NPs retained significantly more Zn than the control group (p < 0.05), lowering feces Zn excretion. The supplementation of ZnO NPs did not reduce lymphoid organs weight; in fact, a notable increase in weight was observed in groups supplemented with higher levels of ZnO NPs when compared to the control group. Furthermore, no significant increase in liver weight (p > 0.05) or enzymatic activities (AST and ALT) were observed in birds fed ZnO NPs, indicating no liver damage occurred. ZnO NPs at 100 mg kg−1 in the diet showed antibacterial effects, reducing Enterococcus spp. and E. coli count significantly, without affecting commensal bacteria (lactic acid bacteria) count. ConclusionThe inclusion of ZnO NPs to broiler chicken feed as a Zn source had no negative effects on growth or health. Additionally, it increased Zn absorption and bioavailability, reduced Zn excretion, and exhibited potential antibacterial activity against tested pathogens.

Zinc Oxide Nanoparticles Induce Renal Injury by Initiating Oxidative Stress, Mitochondrial Damage and Apoptosis in Renal Tubular Epithelial Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in many fields due to their unique physicochemical properties. However, the renal toxicity of ZnO NPs and the underlying mechanisms have not been well studied. We found that ZnO NPs induced injury in human renal proximal tubular epithelial cells (HK-2) in a dose- and size-dependent manner, as revealed by CCK-8, LDH and Annexin V-FITC assays. Mechanistically, ZnO NPs promoted oxidative stress and mitochondrial damage by generating ROS and induced apoptosis in HK-2 cells, as evidenced by the upregulation of Bax and Caspase 3 and downregulation of Beclin 1. In vivo, ZnO NPs induced tubular epithelial cell apoptosis and increased serum creatinine, serum urea nitrogen, and urinary protein in mice, suggesting damage to renal structure and function. These findings clarified our understanding of the biological mechanisms underlying ZnO NP-induced renal tubular epithelial cell injury and contributed to estimating the risk of ZnO NPs to the kidney.

Toxic effects of zinc oxide nanoparticles as a food additive in goat mammary epithelial cells

Zinc oxide nanoparticles (ZnO NPs) have recently been used as food preservatives and additives because of their good antibacterial and nutritional functions. This study performed RNA-seq analyses to evaluate the potential toxicity of ZnO NPs on goat mammary epithelial cells (GMECs) in vitro. Our results suggested that the ZnO NP treatment significantly reduced GMEC viability in a time- and dose-dependent manner. Transcriptomic analysis showed that ZnO NP exposure changed the expression levels of more than 500 genes in GMECs, including various biological pathways. We observed that decreased mitochondrial membrane potential caused mitochondrial dysfunction. Further study indicated that the treatment of cells with ZnO NPs resulted in the accumulation of reactive oxygen species (ROS), which led to oxidative stress. Meanwhile, the expression of genes (TNFα, TNFR1, FADD, Caspase 8 and Caspase 6) associated with the death receptor pathway was upregulated, which indicated the death receptor-mediated extrinsic apoptosis pathway was activated. Moreover, the expression levels of Bax, Cytc, Caspase 3 and Caspase 9 were upregulated, while the expression levels of Bcl2 were downregulated, which indicated mitochondria-mediated intrinsic apoptosis pathway was activated. More notably, ZnO NP exposure increased the expression levels of ER stress-related genes (PERK, ATF4, eIF2α and CHOP) and proteins (p-PERK, p-eIF2α, PERK and CHOP). Furthermore, gene ontology (GO) terms and genes related to autophagy were altered, suggesting that exposure to ZnO NPs might activate autophagy in GMECs. In summary, our findings showed that ZnO NPs could exert significant toxic effects on GMECs through multiple mechanisms. These pathways are related to each other and influence each other to participate in ZnO NPs-induced the damage of GMECs. Thus, their safe use in the feed and food industry should be considered. Meanwhile, RNA-seq might represent a new method of assessing the toxicity mechanisms of nanomaterials.

Ameliorative Effects of some Natural Antioxidants against Blood and Cardiovascular Toxicity of Oral Subchronic Exposure to Silicon Dioxide, Aluminum Oxide, or Zinc Oxide Nanoparticles in Wistar Rats.

The present study determines the possible protective role of fig fruit extract with olive oil and date palm fruit extract (FOD) in decreasing the oral subchronic blood and cardiovascular toxicity of SiO2NPs, Al2O3NPs, or ZnONPs. The present study used 80 male Wistar rats (8 groups, n = 10) distributed according to the treatment. The FOD treatments were used at their recommended antioxidant doses. All nanoparticles (NPs) were given orally and daily at doses of 100 mg/kg for 75 days. The oral administration of different NPs alone led to dramatic, oxidative stress, inflammatory markers, blood coagulation, endothelial dysfunction markers, myocardial enzymes, hematological parameters, lipid profile, and histopathological features compared with the control group. The FOD-NP-treated groups recorded significantly ameliorated blood and cardiovascular toxicity hazards compared to the groups administered with the NPs alone. In conclusion, the administration of FOD provides considerable chemopreventive and ameliorative effects against NP toxicity.

Salinity Moderated the Toxicity of Zinc Oxide Nanoparticles (ZnO NPs) towards the Early Development of Takifugu obscurus

ZnO nanoparticles (ZnO NPs) have been applied in a wide range of fields due to their unique properties. However, their ecotoxicological threats are reorganized after being discharged. Their toxic effect on anadromous fish could be complicated due to the salinity fluctuations during migration between freshwater and brackish water. In this study, the combined impact of ZnO NPs and salinity on the early development of a typical anadromous fish, obscure puffer (Takifugu obscurus), was evaluated by (i) observation of the nanoparticle characterization in salt solution; (ii) quantification of the toxicity to embryos, newly hatched larvae, and larvae; and (iii) toxicological analysis using biomarkers. It is indicated that with increased salinity level in brackish water (10 ppt), the toxicity of ZnO NPs decreased due to reduced dissolved Zn2+ content, leading to higher hatch rate of embryos and survival rate of larvae than in freshwater (0 ppt). The irregular antioxidant enzyme activity changes are attributed to the toxic effects of nanoparticles on CAT (catalase), but further determination is required. The results of present study have the significance to guide the wildlife conservation of Takifugu obscurus population.

Histological and immunohistochemical studies on the effect of zinc oxide nanoparticles on the cerebellum of newborn and adult rats and the possible protective role of EDTA

Zinc oxide nanoparticles (ZnO NPs) are involved in different applications such as nutrition, while, it causes damage to different organs of the body including the brain. This study aimed to compare between the effect of ZnO NPs on newborn and adult rats´ cerebellum and to evaluate the protective role of Ethylenediaminetetraacetic acid (EDTA) against ZnO NPs toxicity. Thirty-two newborn (NBM)and thirty-two adult male (ADM) Sprague Dawley rats are used. Four groups (n = 8) of each are divided as following; Gp1: is served as control, Gp2: injected intraperitoneal (IP) with ZnO NPs (3 g/ kg). Gp3: injected IP with EDTA (500 mg/ kg) for 7 days. Gp4: injected with ZnO NPs and treated with EDTA as in Gp3. Brain tissue is prepared for biochemical and histopathological investigations. Newborn and adult rats injected with ZnO NPs showed degeneration of purkinje and granular cells in cerebellum tissue confirmed with high expression of caspase-3, while, treatment with EDTA post ZnO NPs showed lightly improvement. The body weights and relative brain weights is decrease in all the rats treated with ZnO NPs. In addition, our current study proved that the effect of ZnO NPs on ADM rats is more than on the NBM ones. Collectively, ZnO NPs injection caused damage of the cerebellum in newborn and adult rats, however, the treatment with EDTA stopped somewhat this damage.

Effect of Dietary Moringa oleifera Leaves Nanoparticles on Growth Performance, Physiological, Immunological Responses, and Liver Antioxidant Biomarkers in Nile tilapia (Oreochromis niloticus) against Zinc Oxide Nanoparticles Toxicity

The current study addresses the influence of Moringa oleifera leaves nanoparticles (MO-NPs) on growth, biochemical, immunological, and hepatic antioxidant alterations induced by zinc oxide nanoparticles toxicity in Nile tilapia (O. niloticus). Fish (N = 180) were divided into four groups with replicates. The first one was set as a control group and the second group was fed an MO-NPs-enriched diet (2.5 g/kg diet). The third group was exposed to 8 mg/L ZnO-NPs, while the forth group was exposed to 8 mg/L ZnO-NPs and fed on MO-NPs (2.5 g/kg diet) for 2 months. Exposure of O. niloticus to 8 mg/L ZnO-NPs induced the following consequences: a sharp decrease in the growth parameters; a marked increment in the biochemical biomarkers (glucose, cortisol, and liver enzymes (ALT, AST, ALP); a significant increase in serum renal products, urea and creatinine, cholesterol, and LDH levels. Nonetheless, the dietary MO-NPs supplementation for 2 months significantly alleviated the ZnO-NPs toxicity and significantly enhanced the growth indices, plus normalizing the physio-biochemical levels in the exposed group to ZnO-NPs toxicity to reach the levels of the control group. The MO-NPs markedly improved hepatic antioxidant biomarkers, MDA, and TAC, while, decreasing SOD, CAT, and GSH levels to be near the control values. Moreover, supplemented fish in MO-NPs (2.5 g/kg diet) and exposed to ZnO-NPs provided a remarkable increase in the immune profile (respiratory burst (RB) activity, lysozyme, and total immunoglobulins (IgM)) compared to the ZnO-NPs-intoxicated group. Based on the findings of the study, the exposed O. niloticus to ZnO-NPs were immune-antioxidant-depressed, besides showing growth retardation, and physio-biochemical alterations. On the other hand, a supplemented diet with MO-NPs is a novel approach to ameliorate ZnO-NPs toxicity for sustaining aquaculture and correspondingly protecting human health.

Zinc Oxide Nanoparticles Induce Toxicity in H9c2 Rat Cardiomyoblasts.

Zinc oxide nanoparticles (ZnO NPs) are widely used in the cosmetic industry. They are nano-optical and nano-electrical devices, and their antimicrobial properties are applied in food packaging and medicine. ZnO NPs penetrate the body through inhalation, oral, and dermal exposure and spread through circulation to various systems and organs. Since the cardiovascular system is one of the most vulnerable systems, in this work, we studied ZnO NPs toxicity in H9c2 rat cardiomyoblasts. Cardiac cells were exposed to different concentrations of ZnO NPs, and then the morphology, proliferation, viability, mitochondrial membrane potential (ΔΨm), redox state, and protein expression were measured. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining showed strong morphological damage. ZnO NPs were not observed inside cells, suggesting that Zn2+ ions were internalized, causing the damage. ZnO NPs strongly inhibited cell proliferation and MTT reduction at 10 and 20 μg/cm2 after 72 h of treatment. ZnO NPs at 20 μg/cm2 elevated DCF fluorescence, indicating alterations in the cellular redox state associated with changes in ΔΨm and cell death. ZnO NPs also reduced the intracellular expression of troponin I and atrial natriuretic peptide. ZnO NPs are toxic for cardiac cells; therefore, consumption of products containing them could cause heart damage and the development of cardiovascular diseases.

Different Strategies to Attenuate the Toxic Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells.

Zinc oxide nanoparticles (ZnO NPs) are one of the most used nanoparticles due to their unique physicochemical and biological properties. There is, however, a growing concern about their negative impact on male reproductive health. Therefore, in the present study, two different strategies were used to evaluate the recovery ability of spermatogonia cells from the first stage of spermatogenesis (GC-1 spg cell line) after being exposed to a cytotoxic concentration of ZnO NPs (20 µg/mL) for two different short time periods, 6 and 12 h. The first strategy was to let the GC-1 cells recover after ZnO NPs exposure in a ZnO NPs-free medium for 4 days. At this phase, cell viability assays were performed to evaluate whether this period was long enough to allow for cell recovery. Exposure to ZnO NPs for 6 h and 12 h induced a decrease in viability of 25% and 41%, respectively. However, the recovery period allowed for an increase in cell viability from 16% to 25% to values as high as 91% and 84%. These results strongly suggest that GC-1 cells recover, but not completely, given that the cell viability does not reach 100%. Additionally, the impact of a synthetic chalcone (E)-3-(2,6-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) to counteract the reproductive toxicity of ZnO NPs was investigated. Different concentrations of chalcone 1 (0–12.5 µM) were used before and during exposure of GC-1 cells to ZnO NPs to mitigate the damage induced by NPs. The protective ability of this compound was evaluated through viability assays, levels of DNA damage, and cytoskeleton dynamics (evaluating the acetylated α-tubulin and β-actin protein levels). The results indicated that the tested concentrations of chalcone 1 can attenuate the genotoxicity induced by ZnO NPs for shorter exposure periods (6 h). Chalcone 1 supplementation also increased cell viability and stabilized the microtubules. However, the antioxidant potential of this compound remains to be elucidated. In conclusion, this work addressed the main cytotoxic effects of ZnO NPs on a spermatogonia cell line and analyzed two different strategies to mitigate this damage, which represent a significant contribution to the field of male fertility.

Zinc Oxide Particles Can Cause Ovarian Toxicity by Oxidative Stress in Female Mice Model.

IntroductionZinc oxide nanoparticles (ZnO NPs) participate in all aspects of our lives, but with their wide application, more and more disadvantages are exposed. The goal of this study was to investigate the toxicity of ZnO NPs in female mice ovaries and explore its potential mechanism.MethodsIn this study, adult female mice were orally exposed to 0, 100, 200, and 400 mg/kg ZnO NPs for 7 days. We explored the underlying mechanisms via the intraperitoneal injection of N-acetyl-cysteine (NAC), an inhibitor of oxidative stress, and salubrinal (Sal), an inhibitor of endoplasmic reticulum (ER) stress.ResultsThe results indicated that serum estradiol and progesterone levels declined greatly with increasing ZnO NPs dosage. Hematoxylin and eosin (HE) staining revealed increased atretic follicles and exfoliated follicular granulosa cells. Moreover, at the transcriptional level, antioxidant-related genes such as Keap1 and Nrf2, and ER stress-related genes PERK, eIF2α, and ATF4 were markedly upregulated. In addition, the expression of Caspase12, Caspase9, and Caspase3, which are genes related to apoptosis, was also upregulated in all ZnO NPs treatment groups. Serum malondialdehyde (MDA) content was remarkably up-regulated, whereas superoxide dismutase (SOD) activity was down-regulated. The 400 mg/kg ZnO NPs treatment group suffered the most substantial harm. However, ovarian damage was repaired when NAC and Sal were added to this group.ConclusionZnO NPs had toxic effects on the ovary of female mice, which were due to oxidative stress, ER stress, and the eventual activation of apoptosis.