Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors

Background

Nanomaterials, as a new kind of materials, have been greatly applied in different fields due to their special properties. With the industrialization of nanostructured materials and increasing public exposure, the biosafety and potential influences on central nervous system (CNS) have received more attention. Nanosized zinc oxide (nanoZnO) was suggested to up-regulate neuronal excitability and to induce glutamate release in vitro. Therefore, we hypothesized nanoparticles of nanoZnO may lead to changes in balance of neurotransmitter or neuronal excitability of CNS. This study was to investigate if there were effects of nanoZnO on animal model of depression.

Methods

Male Swiss mice were given lipopolysaccharides (LPS, 100 μg/kg, 100 μg/ml, every other day, 8 times, i.p.) from weaning to induce depressive-like behaviors. NanoZnO (5.6 mg/kg, 5.6 mg/ml, every other day, 8 times, i.p.) was given as the interaction. The mouse model was characterized using the methods of open field test, tail suspension test and forced swim test. Furthermore, the spatial memory was evaluated using Morris water maze (MWM) and the synaptic plasticity was assessed by measuring the long-term potentiation (LTP) in the perforant pathway (PP) to dentate gyrus (DG) in vivo.

Results

Results indicated that model mice showed disrupted spatial memory and LTP after LPS injections and the behavioral and electrophysiological improvements after nanoZnO treatment.

Conclusion

Data suggested that nanoZnO may play some roles in CNS of mental disorders, which could provide some useful direction on the new drug exploring and clinical researches.     

Antimicrobial activity of silymarin mediated zinc oxide and hydroxy apatite nanoparticles against oral pathogens

The nanoparticles such as hydroxyapatite, zinc oxide, titanium dioxide and zirconium nanoparticles have application in dentistry. Therefore, it is of interest to document the antimicrobial activity of silymarin mediated zinc oxide and hydroxy apatite nanoparticles against oral pathogens. Hence, we synthesized hydroxyapatie and zinc oxide nanoparticles with silymarin and characterized by UV-visible spectrophotometer. Data shows that silymarin mediated HAP and ZnO nanoparticles have antimicrobial activity against oral pathogens such as Pseudomonas sp, Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis and Candida albicans.     

BSA‐conjugated zinc oxide nanoparticles as luminescent probes for the determination of histidine

Zinc oxide nanoparticles doped with bovine serum albumin were used to determine histidine in aqueous solutions using a fluorescence spectroscopic technique. The results showed that histidine effectively quenched the fluorescence of the modified ZnO nanoparticles, whereas other amino acids did not significantly affect the light emission, thereby allowing selective and sensitive histidine detection in amino acid mixtures. Under optimal conditions (pH 7.0, 25 °C, 10 min preincubation), the detection limit for histidine was ~ 9.87 × 10^–7 mol/L. The high value of the determined quenching rate constant K_q (3.30 × 10¹³ L/mol/s) was consistent with a static quenching mechanism. Copyright © 2015 John Wiley & Sons, Ltd.     

纳米氧化锌经口染毒对C57BL/6J小鼠外周脏器的影响*

目的:探讨纳米氧化锌经口染毒60 d对C57BL/6J小鼠多种外周脏器的损伤作用。方法:20只雄性C57BL/6J小鼠随机分为对照组和实验组,每组10只,实验组将纳米氧化锌溶液以20 mg/kg体重的剂量连续灌胃染毒60 d,对照组给予相应量的生理盐水;小鼠每周称重一次,染毒结束后,眼球取血,检测血糖、血脂、肝功能和肾功能相关指标,以及血清中炎症因子PAF、IL-6和TNF-α含量;取心脏、肝脏、脾脏、肺、肾脏和小肠组织制备病理切片,HE染色后,观察组织形态学变化。结果:实验组和对照组之间的体重无显著性差异;与正常对照组比较,实验组大鼠血中白蛋白(ALB)、白蛋白/球蛋白比值(A/G)、碱性磷酸酶(ALP)、谷草/谷丙转氨酶比值(S/L)、尿酸(UA)和尿素氮(BUN)含量明显升高(P＜0.05或 P＜0.01);两组间血清中炎症因子含量无显著差异。病理学检查发现,实验组心肌中部分区域出现浊肿,肝脏出现轻度炎性病变(灶性或小灶性坏死),脾脏色素沉着减少,肺部出现轻或中度间质性炎症,肾脏和小肠未见明显病理改变。结论:纳米氧化锌经口染毒60 d未引起C57BL/6J小鼠血液系统炎症,但可诱导心脏、肝脏、脾脏和肺脏出现轻度的病理变化,并导致肝脏和肾脏的功能异常。     

Green synthesis and characterization of zinc oxide nanoparticles using Cayratia pedata leaf extract

The synthesis of Zinc oxide nanoparticles using a plant-mediated approach is presented in this paper. The nanoparticles were successfully synthesized using the Nitrate derivative of Zinc and plant extract of the indigenous medicinal plant Cayratia pedata. 0.1 mM of Zn (NO₃)₂.6H₂O was made to react with the plant extract at different concentrations, and the reaction temperature was maintained at 55 °C, 65 °C, and 75 °C. The yellow coloured paste obtained was wholly dried, collected, and packed for further analysis. In the UV visible spectrometer (UV–Vis) absorption peak was observed at 320 nm, which is specific for Zinc oxide nanoparticles. The characterization carried out using Field Emission Scanning Electron Microscope (FESEM) reveals the presence of Zinc oxide nanoparticles in its agglomerated form. From the X-ray diffraction (XRD) pattern, the average size of the nanoparticles was estimated to be 52.24 nm. Energy Dispersive Spectrum (EDX) results show the composition of Zinc and Oxygen, giving strong energy signals of 78.32% and 12.78% for Zinc and Oxygen, respectively. Fourier Transform - Infra-Red (FT-IR) spectroscopic analysis shows absorption peak of Zn–O bonding between 400 and 600 cm^?1. The various characterization methods carried out confirm the formation of nano Zinc oxide. The synthesized nanoparticles were used in the immobilization of the enzyme Glucose oxidase. Relative activity of 60% was obtained when Glucose oxidase was immobilized with the green synthesized ZnO nanoparticles. A comparative study of the green synthesized with native ZnO was also carried out. This green method of synthesis was found to be cost-effective and eco-friendly.     

Antibacterial activities of zinc oxide nanoparticles against Escherichia coli O157:H7

Aims:  To investigate antibacterial activities of zinc oxide nanoparticles (ZnO NP) and their mode of action against an important foodborne pathogen, Escherichia coli O157:H7.
Methods and Results:  ZnO NP with sizes of 70 nm and concentrations of 0, 3, 6 and 12 mmol l⁻¹ and NP-free solutions were used in antimicrobial tests against E. coli O157:H7. ZnO NP showed increasing inhibitory effects on the growth of E. coli O157:H7 as the concentrations of ZnO NP increased. A complete inhibition of microbial growth was achieved at the concentration level of 12 mmol l⁻¹ or higher. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy were used to characterize the changes of morphology and cellular compositions of bacterial cells treated with ZnO NP and study the mode of action of ZnO NP against E. coli O157:H7. The intensity of lipid and protein bands in the Raman spectra of bacterial cells increased after exposure to ZnO NP, while no significant changes in nucleic acid bands were observed.
Conclusions:  ZnO NP were found to have antibacterial activity against E. coli O157:H7. The inhibitory effects increase as the concentration of ZnO NP increased. Results indicate that ZnO NP may distort and damage bacterial cell membrane, resulting in a leakage of intracellular contents and eventually the death of bacterial cells.
Significance and Impact of the Study:  These results suggest that ZnO NP could potentially be used as an effective antibacterial agent to protect agricultural and food safety.     

Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

The use of titanium dioxide (TiO₂) in various industrial applications (eg, production of paper, plastics, cosmetics, and paints) has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO₂ nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO₂ micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO) nanoparticles were the most effective, TiO₂ nanoparticles the second most effective, and magnesium oxide (MgO) nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO₂ micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.     

Fungicidal synergistic effect of biogenically synthesized zinc oxide and copper oxide nanoparticles against Alternaria citri causing citrus black rot disease

Citrus black rot disease being caused by Alternaria citri is a major disease of citrus plants with 30–35% economic loss annually. Fungicides had not been effective in the control of this disease during last few decades. In the present study, antifungal role of green synthesized zinc oxide (ZnO) and copper oxide (CuO) nanoparticles (NPs) were studied against Alternaria citri. Alternaria citri was isolated from disease fruits samples and was identified by staining with lacto phenol cotton blue. Furthermore, CuO and ZnO NPs were synthesized by utilizing the lemon peels extract as the reducing and capping agent. Nanoparticles were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. From the XRD data, the calculated size of CuO NPs was to be 18 nm and ZnO NPs was16.8 nm using Scherrer equation. The SEM analyses revealed the surface morphology of all the metal oxide NPs synthesized were rounded, elongated and or spherical in the shape. The zone of inhibition was observed to be 50 ± 0.5 mm by CuO NPs, followed by 51.5 ± 0.5 mm by ZnO NPs and maximum zone of antifungal inhibition was observed to be 53 ± 0.6 mm by mix metal oxide NPs. The results of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of the synthesized nanoparticles showed that at the certain concentrations (80 mg ml^?1), these NPs were capable of inhibiting the fungal growth, whereas above that specified concentrations (100 mg ml^?1), NPs completely inhibited the fungal growth. Based on these findings, the green synthesized NPs can be used as alternative to fungicide in order to control the citrus black rot disease.     

Effects of zinc on cell proliferation and proteoglycan characteristics of epiphyseal chondrocytes

Zinc has been postulated as an important nutritional factor involved in growth promotion; however, the cellular mechanisms involved in the effects of zinc on linear growth remain to be elucidated. This study was conducted to evaluate the effects of zinc on the proliferation rate of epiphyseal growth plate chondrocytes and on the structural characteristics of the proteoglycans synthesized by these cells. For these purposes, hypertrophic and proliferating chondrocytes were isolated from the tibiae of 1- and 5-week-old chickens, respectively. Chondrocytes were cultured under serum-free conditions and primary cultures were used. The results showed that zinc stimulated proliferation by 40-50% above the baseline in the case of proliferating chondrocytes, but it had no effect on hypertrophic chondrocytes. Zinc had neither any effects on mean charge density of proteoglycans synthesized by hypertrophic chondrocytes nor in their hydrodynamic size. In contrast, zinc induced an increase in mean charge density and a decrease of hydrodynamic size of proteoglycans synthesized by proliferating chondrocytes. In both cell types zinc had no effect on the composition and hydrodynamic size of the glycosaminoglycan chains. The increased ability of proliferating chondrocytes cultured in the presence of zinc to synthesize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) could be explained by the induction of enzymes participating in the sulfation pathway of proteoglycans. Therefore, the increase in mean charge density of proteoglycans observed in this study may be explained by an increase of the degree of sulfation of proteoglycan molecules. We speculate that the effect of zinc on linear growth may be explained at a cellular level by: a) an increase in proliferation rates of proliferating chondrocytes, and b) increased synthesis of highly charged proteoglycan molecules which decreases mineralization.     

Tissue and blood levels of zinc, copper, and magnesium in nitric oxide synthase blockade-induced hypertension

The aim of this study was to determine the levels of tissue and blood zinc (Zn), copper (Cu), magnesium (Mg) in nitric oxide (NO) synthase blockade-induced hypertension. A group of albino rats received a NO synthase inhibitor, N ^G -nitro-l-arginine-methyl ester (l-NAME, 60 mg/kg/d) in their drinking water for 21 d. l-NAME intake caused a progressive rise in this group’s resting mean arterial blood pressure compared to a control group (p<0.01). There were no differences between the groups with regard to tissue and blood levels of Zn or Cu; however, Mg concentrations were significantly lower in the hypertensive rats’ erythrocytes (20.2% reduction from control levels), cerebral cortex (17.0%), heart (9.1%), renal cortex (12%), renal medulla (16.7%), and in the tissues of the caval vein (23.7%), mesenteric artery (29.8%), renal artery (18.4%), and renal vein (22.1%). There were no significant Mg concentration changes in the hypertensive group’s plasma, cerebellum, liver, duodenum, or aortal tissue. These findings suggest that Mg depletion may play a role in the blood pressure rise that occurs in the model of chronic NO synthase inhibition-induced hypertension.     

Sepsis inhibits reduction of dehydroascorbic acid and accumulation of ascorbate in astroglial cultures: intracellular ascorbate depletion increases nitric oxide synthase induction and glutamate uptake inhibition

Sepsis is associated with oxidative stress and impaired glutamatergic transmission in brain. We investigated whether sepsis impairs accumulation of the antioxidant, ascorbate, and uptake of glutamate by astrocytes. Bacterial endotoxin (Escherichia coli lipopolysaccharide, LPS) and the inflammatory cytokine, interferon-gamma (IFNgamma), were applied to primary astrocyte cultures to model sepsis. In the absence of ascorbate, the combination of LPS and IFNgamma (LPS + IFNgammay) up-regulated inducible nitric oxide synthase (iNOS) and decreased the initial rate of glutamate uptake by 50% within 24 h. Cell viability and facilitated glucose transport activity were not affected at 24 h. Pre-treatment with ascorbate-2-O-phosphate increased intracellular ascorbate concentration and attenuated the induction of iNOS and inhibition of glutamate uptake caused by LPS + IFNgamma. Subsequent experiments examined the mechanisms by which cells accumulate ascorbate. LPS + IFNy decreased slightly the initial rate of uptake of ascorbate and inhibited markedly the rate with which intracellular dehydroascorbic acid (DHAA) was reduced to ascorbate. We conclude that septic insult impairs astrocytic clearance of DHAA from the extracellular fluid and decreases intracellular ascorbate concentration. Furthermore, sepsis induces iNOS and inhibits glutamate uptake by astrocytes through mechanisms that can be modulated by intracellular ascorbate. These results indicate treatments that increase intracellular ascorbate concentration may be beneficial for patients at risk for neurologic complication in sepsis.     

Biofabrication of zinc oxide nanoparticles from Melia azedarach and its potential in controlling soybean seed-borne phytopathogenic fungi

Present study, report the biofabrication of zinc oxide nanoparticles from aqueous leaf extract of Melia azedarach (MaZnO-NPs) through solution combustion method and their novel application in preventing the growth of seed-borne fungal pathogens of soybean (Cladosporium cladosporioides and Fusarium oxysporum). The standard blotter method was employed to isolate fungi and was identified through molecular techniques. The characterization of MaZnO-NPs was carried out by UV–Vis spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) equipped with Energy Dispersive Spectroscopy (EDS) and Transmission Electron Microscopy (TEM). The physicochemical characterization confirmed the particles were of high purity and nano size (30–40 nm) with a hexagonal shape. The synthesized MaZnO-NPs inhibited the growth of C. cladosporioides and F. oxysporum in a dose dependent manner. Biomass, ergosterol, lipid peroxidation, intracellular reactive oxygen species and membrane integrity determination upon MaZnO-NPs treatment offered significant activities there by confirming the mechanism of action against the test pathogens. In conclusion, due to the effectiveness of MaZnO-NPs in controlling the growth of C. cladosporioides and F. oxysporum, the synthesized MaZnO-NPs provides insight towards their potential application in agriculture and food industries.     

Vitamins E and C ameliorate the oxidative stresses induced by zinc oxide nanoparticles on liver and gills of Oreochromis niloticus

The current study evaluated the hazards of Zinc oxide nanoparticles (ZnONPs) on Nile Tilapia liver and gill antioxidants enzymes activities and antioxidants genes expressions. The ameliorative action of vitamins E and C mixture was investigated. Two hundred males of Nile Tilapia were exposed to one and two mg?L^?1 of ZnONPs either with or without vitamin C and E mixture for 7 and 15?days. Glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and gene expression as well glutathione (GSH) and lipid peroxide (LPO) levels were investigated. The results revealed that the exposure to ZnONPs could induce alterations in the liver and gills antioxidants and LPO of Nile Tilapia. Moreover, the mixture of vitamin E and C highly effective in alleviation the toxic effect of ZnONPs.     

Evaluation of the effects of pharmacological zinc oxide and phosphorus source on weaned piglet growth performance,plasma minerals and mineral digestibility

Crossbred pigs (n=720; average age=28±3 days and weight=9.5±0.3 kg) were used in a 20-day trial in order to determine the influence of phosphorus (P) source and various doses of pharmacological zinc (Zn) on growth performance, plasma minerals and mineral digestibility. Pigs (five intact males and five females per pen) were randomly allotted to treatments in a 3×3 factorial arrangement with three sources of dietary P (4.5 g/kg digestible P, 4.5 g/kg digestible P plus 2500 phytase units (FTU)/kg, or 5.5 g/kg digestible P) and three dietary levels of supplemental Zn (0, 1750 or 3500 mg/kg) from ZnO (82% Zn) with eight pens per treatment. Diets were formulated to exceed all nutrient requirements, including calcium (Ca), P and Zn from day 0 to 20. Zn supplementation increased (quadratic P<0.05) average daily feed intake. There was a significant Zn level×P source interaction on average daily gain and feed conversion ratio (FCR). Pigs fed 4.5 g/kg digestible P without or with 2500 FTU/kg phytase gained more per day (quadratic P<0.05) and had better FCR (quadratic P<0.05) when they were fed 1750 mg/kg supplemental Zn. However, pigs fed 5.5 g/kg digestible P gained more per day (linear P<0.05) and were more efficient (linear P<0.05) when they were fed 3500 mg/kg supplemental Zn. Plasma Zn and Zn digestibility increased (linear P<0.05) as pharmacological Zn supplementation increased from 0 to 3500 mg/kg, irrespective of P source. However, Ca, P, sodium (Na), potassium (K) and copper (Cu) digestibility were reduced (P<0.05) as pharmacological Zn supplementation increased, and this was mitigated or exacerbated by the supplementation of 5.5 g/kg digestible P or phytase. In conclusion, increasing the dietary inclusion of pharmacological Zn may impact growth performance in young pigs through the interaction with minerals such as Ca, P, Na and K. Pharmacological Zn may reduce Na or K digestibility and indirectly reduce water secretion into the lumen, resulting in an increase in faecal dry matter as pharmacological Zn supplementation in the diet increased.     

Aluminium oxide nanoparticles inhibit EPS production,adhesion and biofilm formation by multidrug resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a biofilm forming multidrug resistant (MDR) pathogen responsible for respiratory tract infections. In this study, aluminium oxide nanoparticles (Al₂O₃ NPs) were synthesized and characterized by TEM and EDX and shown to be spherical shaped nanoparticles with a diameter < 10?nm. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) for the Al₂O₃ NPs ranged between 125 and 1,000?µg ml^?1. Exposure to NPs caused cellular membrane disruption, indicated by an increase in cellular leakage of the contents. Biofilm inhibition was 11.64 to 70.2%, whereas attachment of bacteria to polystyrene surfaces was reduced to 48.8 to 51.9% in the presence of NPs. Nanoparticles also reduced extracellular polymeric substance production and the biomass of established biofilms. The data revealed the non-toxic nature of Al₂O₃ NPs up to a concentrations of 120?µg ml^?1 in HeLa cell lines. These results demonstrate an effective and safer use of Al₂O₃ NPs against the MDR A. baumannii by targeting biofilm formation, adhesion and EPS production.     

Effect of rearing environment and dietary zinc oxide on the response of group-housed weaned pigs to enterotoxigenic Escherichia coli O149 challenge

A 2 × 2 factorial experiment was conducted to determine the effects of rearing environment (indoor (In) v. outdoor (Out)) and dietary zinc oxide (ZnO) supplementation (0 (-Zn) v. 3100 (+Zn) mg/kg feed) on the response of weaned pigs to a challenge infection with enterotoxigenic Escherichia coli (ETEC). Pigs from the two rearing environments were weaned onto trial diets at 4 weeks of age, moved into conventional accommodation and infected 3 days later with 109 CFU ETEC per os. Faecal ETEC shedding was determined before and after challenge. After 7 days of ETEC infection, all pigs were euthanized for gut lactic acid bacteria (LAB)-to-coliform ratio, pH and small intestine morphological measurements. Both ZnO and outdoor rearing reduced ETEC excretion, and these effects were additive. Outdoor rearing increased small intestine and colon tissue weight. ZnO increased villus height and goblet cell number in the upper small intestine, LAB-to-coliform ratio (through reduced coliforms) in the lower small intestine and proximal colon, and improved growth performance. There were interactive effects of rearing environment and ZnO supplementation on upper small intestine villus height and daily gain, as outdoor rearing conferred advantages on these variables only with ZnO dietary supplementation. Daily gains were 233, 174, 277 and 347 (s.e.m. 27.2) g/day for the In - Zn, Out - Zn, In + Zn and Out + Zn, respectively. These results suggest different, but complementary mechanisms of intestinal health and performance in outdoor-reared pigs and those offered ZnO supplemented diets. The results indicate that the benefits of ZnO to the weaned pig extend beyond suppression of ETEC and appear mediated through altered development of the small intestine mucosa.     

Decreased fibroblast and increased osteoblast adhesion on nanostructured NaOH-etched PLGA scaffolds

To facilitate locomotion and support the body, the skeleton relies on the transmission of forces between muscles and bones through complex junctions called entheses. The varying mechanical and biological properties of the enthesis make healing this avascular tissue difficult; hence the need for an engineered alternative. Cells in situ interact with their environment on the nano-scale which suggests that engineered approaches to enthesis regeneration should include such biologically-inspired nano-scale surface features. The present in vitro study investigated the effects of etching poly-lactic-co-glycolic acid (PLGA) scaffolds to produce nano-topography on the adhesion of fibroblasts and osteoblasts, two integral enthesis cell types. Nano-topography was produced on PLGA by etching the scaffolds in NaOH. Results showed that etching PLGA with NaOH to create nano-scale surface features decreased fibroblast adhesion while it increased osteoblast adhesion; criteria critical for the spatial control of osteoblast and fibroblast adhesion for a successful enthesis tissue engineering material. Thus, the results of this study showed for the first time collective evidence that PLGA can be either treated with NaOH or not on ends of an enthesis tissue engineering construct to spatially increase osteoblast and fibroblast adhesion, respectively.