Toxicity assessment of zinc sulfate: A commonly used compound.

Because zinc sulfate (ZnSO4) is widely used in many fields such as biomedicine, electronics, and chemistry, it is important to evaluate its toxic effects. In this study, the cyto-genotoxic effects of ZnSO4 on meristematic cells in the root tip of Allium cepa L. were investigated. After calculating the effective concentration (EC50 = 70 ppm) of ZnSO4, A. cepa root tip cells were suspended for 24, 48, 72, and 96 h in solutions of 35 ppm (EC50/2), 70 ppm (EC50), and 140 ppm (EC50 × 2) concentrations. Using the counts of dividing cells, the mitotic index (MI) was calculated. Chromosome aberration index (CAI) was determined from percentages of abnormal cells. When the obtained data were statistically evaluated, it was determined that all application concentrations caused a significant decrease in MI and an increase in CAI compared to the control group (distilled water). It was concluded that increased ZnSO4 dose concentrations and exposure times caused cytotoxicity and genotoxicity in the root cells of A. cepa L.

Sulfated polysaccharides of some seaweeds exhibit neuroprotection via mitigation of oxidative stress, cholinergic dysfunction and inhibition of Zn - induced neuronal damage in HT-22 cells.

BACKGROUND: Sulfated polysaccharides from marine algae are known to possess antioxidative activities, however, their therapeutic role in metal-induced neurodegeneration has not been explored. In this study, the neuroprotective potentials of sulfated polysaccharides isolated from Ecklonia maxima (PKPM), Gelidium pristoides (PMNP), Ulva lactuca (PULV), Ulva rigida (PURL) and Gracilaria gracilis (PGCL) against Zn-induced neurodegeneration in rats' hippocampal neuronal cells (HT-22) were assessed. METHODS: Cells were cultured and maintained at 37 °C. Control cells did not contain Zinc sulphate (ZnSO4) while other experimental groups contain Zn (50 µM) alone or in combination with sulfated polysaccharides (0.4 or 0.8 mg/mL). Cell viability was assessed using MTT assay while apoptotic assay was also determined using acridine orange and ethidium bromide staining technique. Oxidative stress parameters (superoxide dismutase and catalase activities, glutathione and nitric oxide levels) and acetylcholinesterase activity were also assessed in neuronal cells treated with or without Zn. RESULTS: Zn significantly reduced cell viability to about 50%. However, sulfated polysaccharides improved cell viability to about 95%. The sulfated polysaccharides also prevented late apoptosis and necrosis triggered by Zn. Furthermore, superoxide dismutase and catalase activities including glutathione content were significantly low in cells induced with Zn. Treatment with sulfated polysaccharides triggered a significant increase in antioxidant enzymes and glutathione content as well as a decrease in the activity of acetylcholinesterase in cells treated with Zn. CONCLUSION: PKPM, PGCL, PURL, PULV and PMNP exhibit neuroprotective effects against neuronal damage induced by Zn and this may be attributed to inhibition of apoptosis, oxidative damage and acetylcholinesterase activity. These polysaccharides may be good therapeutic agents to protect neuronal cells against Zn - induced pathological processes associated with Alzheimer's disease.

Comparative toxicity of organic, inorganic and nanoparticulate zinc following dietary exposure to common carp (Cyprinus carpio).

This study was carried out to compare the dietary toxicity of organic zinc (Zn-proteinate, Bioplex Zn®), mineral zinc (ZnSO4), and nanoparticulate zinc (ZnO-NPs) on the basis of some biological responses including growth performance and whole-body proximate composition, and antioxidant enzymes, as well as their accumulative affinity to target organs. These Zn sources with the nominal concentrations of 0, 30, 100, and 500 mg kg-1 diet were added to a basal diet. Juvenile common carp (n = 400; weight of 25.3 ±â€¯2.7 g) were fed with the diets for 56 days. ZnSO4 significantly reduced condition factor (CF) at 500 mg kg-1 diet. The highest activity of superoxide dismutase (SOD) and alkaline phosphatase (ALP) was observed in the plasma of the animals received 500 mg kg-1 diet of all experimental Zn sources. However, this concentration of ZnO-NPs significantly increased the activity of SOD when compared to the respective amount of ZnSO4 and Zn-proteinate. Catalase (CAT) showed a zinc-concentration decreasing activity; the minimum activity was observed in the fish group treated with the diet containing 500 mg kg-1 ZnSO4. Digestive, muscular, and integumentary systems demonstrated the following tissue zinc burden: liver > muscle > bone > posterior intestine ≈ skin > anterior intestine, for ZnO-NPs; liver > muscle ≈ bone ≈ posterior intestine ≈ skin > anterior intestine, for Zn-proteinate; and liver > muscle ≈ bone ≈ skin > posterior intestine ≈ anterior intestine, for ZnSO4. Based on accumulative affinity, taken together, ZnO-NPs displayed the highest affinity to all of the analyzed target organs, and also intestinal Zn accumulation suggested that the gut tissue has the lowest rendering ability against ZnO-NPs in compare to ZnSO4 and Zn-proteinate.

Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model.

Olfactory loss is known to affect both mood and quality of life. Transient anosmia was induced in mice to study the resulting changes in mood, behavior, and on a molecular level. Transient anosmia was induced by a single intranasal instillation of ZnSO4 in BALB/c mice. Hematoxylin and eosin (HE) staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression-related behavior; while the open field, and elevated plus maze tests were used to evaluate anxiety-related behavior. The mRNA levels of amygdalar corticotropin-releasing hormone (CRH) and hypothalamic glucocorticoid receptor (GR) were quantified using real-time PCR to confirm relevant molecular change. Olfactory loss was confirmed 1-2.5 weeks after induction, and this loss was subsequently reversed over time. The results of the behavioral tests indicated increased depression-like and reduced anxiety-like behavior at week 1. Accordingly, PCR data identified decreased amygdalar CRH expression at week 1. These results suggest that transient anosmia induces both depressive and anxiolytic behavior as a result of decreased amygdalar CRH in a mouse model of anosmia.

Chronic High Dose Zinc Supplementation Induces Visceral Adipose Tissue Hypertrophy without Altering Body Weight in Mice.

The trace element zinc plays an important role in human life. Zinc deficiency impairs growth, reproduction, metabolism and immunity in both human and animals. Thus, zinc supplementation is recommended in daily life. However, the effect of long-term chronic zinc supplementation on adipose homeostasis has not been well elucidated. In the current study, mice were supplemented with zinc sulfate in the drinking water for 20 weeks. The results suggested that chronic zinc supplementation impaired systemic glucose clearance after exogenous insulin or glucose challenges, as compared to the control mice. Further study revealed that chronic zinc supplementation made no difference to body weight, but increased visceral adipose tissue weight and adipocyte size. In addition, gene expression of leptin and IL6 in the visceral adipose tissue of zinc-supplemented mice were higher than those of control mice. Moreover, serum level of leptin of the zinc-supplemented mice was twice as high as that of the control mice. Besides, phosphorylation level of AKT T308 was attenuated in the perirenal adipose tissue of zinc-supplemented mice. In comparison, the expression of macrophage marker genes and lipogenic genes were not affected by chronic zinc supplementation, but the protein levels of FAS and SCD1 decreased or tended to decrease in the perirenal adipose tissue of zinc-supplemented mice, as compared to the control mice. Our findings suggest that chronic high dose zinc supplementation induces visceral adipose tissue hypertrophy and impairs AKT signaling in perirenal adipose tissue.

Phenotypic and biochemical alterations in relation to MT2 gene expression in Plantago ovata Forsk under zinc stress.

Plantago ovata Forsk is an annual herb with immense medicinal importance, the seed and husk of which is used in the treatment of chronic constipation, irritable bowel syndrome, diarrhea since ancient times. Zinc, an essential metal, is required by plants as they form important components of zinc finger proteins and also aid in synthesis of photosynthetic pigments such as chlorophyll. However, in excess amount Zn causes chlorosis of leaf and shoot tissues and generate reactive oxygen species. The present study is aimed at investigating the changes in expression levels of MT2 gene in Plantago ovata under zinc stress. Data show up to 1.66 fold increase in expression of PoMT2 in 1000 µM ZnSO4·7H2O treated sample. Our study also describes alteration of MT2 gene expressions in Plantago ovata as observed through Real time PCR (qPCR) done by [Formula: see text] method. In this study we have observed an upregulation (or induction) in the PoMT2 gene expression level in 500 and 800 µM ZnSO4·7H2O treated samples but found saturation on further increasing the dose to 1000 µM of ZnSO4·7H2O. Determination of the phenotypic and biochemical changes in Plantago ovata due to exposure to zinc stress of concentrations 500, 800 and 1000 µM revealed oxidative stress. The enhanced expression of MT2 gene in Plantago ovata has a correlation with the increased total antioxidant activity and increased DPPH radical scavenging activity.

In vivo toxicity assessment of non-cadmium quantum dots in BALB/c mice.

Along with widespread usage of QDs in electronic and biomedical industries, the likelihood of QDs exposure to the environment and humans is deemed to occur when the QD products are degraded or handled as waste for processing. To date, there are very few toxicological reports available in the literature for non-cadmium QDs in animal models. In this work, we studied the long term in vivo toxicity of InP/ZnS QDs in BALB/c mice. The biodistribution, body weight, hematology, blood biochemistry, and organ histology were determined at a very high dosage (25 mg/kg) of InP/ZnS QDs over 84 days period. Our results manifested that the QDs formulation did not result in observable toxicity in vivo within the evaluation period, thereby suggesting that the InP/ZnS QDs can be utilized as optical probes or nanocarrier for selected in vivo biological applications when an optimized dosage is employed. FROM THE CLINICAL EDITOR: This study investigated the toxicity of quantum dots in BALB/c mice, and concluded that no organotoxicity was detectable despite of using high concentration of InP/ZnS quantum dots with prolonged exposure of 3 months.

Anxiolytic-like effect of inhalation of essential oil from Lavandula officinalis: investigation of changes in 5-HT turnover and involvement of olfactory stimulation.

Essential oil extracted from Lavandula officinalis (LvEO) has a long history of usage in anxiety alleviation with good evidence to support its use. However, findings and information regarding the exact pathway involved and mechanism of action remain inconclusive. Therefore, we aimed to (1) reveal the influence of olfactory stimulation, and (2) determine whether the serotonergic system is involved in the anxiolytic effect of LvEO when it is inhaled. To this end, we first compared the anxiety-related behaviors of normosmic and anosmic mice. LvEO inhalation caused notable elevation in anxiety-related parameters with or without olfactory perception, indicating that olfactory stimulation is not necessarily required for LvEO to be effective. Neurochemical analysis of the serotonin (5-HT) turnover rate, accompanied by EPM testing, was then performed. LvEO significantly increased the striatal and hippocampal levels of 5-HT and decreased turnover rates in accordance with the anxiolytic behavioral changes. These results, together with previous findings, support the hypothesis that serotonergic neurotransmission plays a certain role in the anxiolytic properties of LvEO.

[Efficacy of using zinc oxide nanoparticles in nutrition. Experiments on the laboratory animal].

In experiments on rats there was researched bioavailability of zinc oxide (ZnO) nanoparticles. There were determined the content of Zn in blood serum and tibia, intestinal uptake of macromolecules of egg albumin, some hematological, biochemical and immune indices, liver cells apoptosis. The results obtained show that the uptake of nanoparticles of ZnO enables restoration of this microelement status damaged by zinc deficit diet.

Effects of zinc toxicity on sugar beet (Beta vulgaris L.) plants grown in hydroponics.

The effects of high Zn concentration were investigated in sugar beet (Beta vulgaris L.) plants grown in a controlled environment in hydroponics. High concentrations of Zn sulphate in the nutrient solution (50, 100 and 300 microm) decreased root and shoot fresh and dry mass, and increased root/shoot ratios, when compared to control conditions (1.2 microm Zn). Plants grown with excess Zn had inward-rolled leaf edges and a damaged and brownish root system, with short lateral roots. High Zn decreased N, Mg, K and Mn concentrations in all plant parts, whereas P and Ca concentrations increased, but only in shoots. Leaves of plants treated with 50 and 100 microm Zn developed symptoms of Fe deficiency, including decreases in Fe, chlorophyll and carotenoid concentrations, increases in carotenoid/chlorophyll and chlorophyll a/b ratios and de-epoxidation of violaxanthin cycle pigments. Plants grown with 300 microm Zn had decreased photosystem II efficiency and further growth decreases but did not have leaf Fe deficiency symptoms. Leaf Zn concentrations of plants grown with excess Zn were high but fairly constant (230-260 microg.g(-1) dry weight), whereas total Zn uptake per plant decreased markedly with high Zn supply. These data indicate that sugar beet could be a good model to investigate Zn homeostasis mechanisms in plants, but is not an efficient species for Zn phytoremediation.

Systemic imbalance of essential metals and cardiac gene expression in rats following acute pulmonary zinc exposure.

It was recently demonstrated that particulate matter (PM) containing water-soluble zinc produces cardiac injury following pulmonary exposure. To investigate whether pulmonary zinc exposure produces systemic metal imbalance and direct cardiac effects, male Wistar Kyoto (WKY) rats (12-14 wk age) were intratracheally (IT) instilled with saline or 2 micromol/kg zinc sulfate. Temporal analysis was performed for systemic levels of essential metals (zinc, copper, and selenium), and induction of zinc transporter-2 (ZT-2) and metallothionein-1 (MT-1) mRNA in the lung, heart, and liver. Additionally, cardiac gene expression profile was evaluated using Affymetrix GeneChips (rat 230A) arrays to identify zinc-specific effects. Pulmonary zinc instillation produced an increase in plasma zinc to approximately 20% at 1 and 4 h postexposure with concomitant decline in the lung levels. At 24 and 48 h postexposure, zinc levels rose significantly (approximately 35%) in the liver. At these time points, plasma and liver levels of copper and selenium also increased significantly, suggesting systemic disturbance in essential metals. Zinc exposure was associated with marked induction of MT-1 and ZT-2 mRNA in lung, heart, and liver, suggesting systemic metal sequestration response. Given the functional role of zinc in hundreds of proteins, the gene expression profiles demonstrated changes that are expected based on its physiological role. Zinc exposure produced an increase in expression of kinases and inhibition of expression of phosphatases; up- or downregulation of genes involved in mitochondrial function; changes in calcium regulatory proteins suggestive of elevated intracellular free calcium and increases in sulfotransferases; upregulation of potassium channel genes; and changes in free radical-sensitive proteins. Some of these expression changes are reflective of a direct effect of zinc on myocardium following pulmonary exposure, which may result in impaired mitochondrial respiration, stimulated cell signaling, altered Ca2+ homeostasis, and increased transcription of sulfotransferases. Cardiotoxicity may be an outcome of acute zinc toxicosis and occupational exposures to metal fumes containing soluble zinc. Imbalance of systemic metal homeostasis as a result of pulmonary zinc exposure may underlie the cause of extrapulmonary effects.

Localization of Triton-insoluble cAMP-dependent kinase type RIbeta in rat and mouse brain.

In eukaryotic cells, cAMP regulates many different cellular functions. Its effects are in most cases mediated by cAMP-dependent protein kinases. These consist of two regulatory and two catalytic subunits. In mammals, four different isoforms of cAMP-dependent protein kinases regulatory subunits have been characterized (RIalpha and beta, RIIalpha and beta). These four isoforms show a high level of homology and slightly different biochemical properties. In addition to biochemical properties, a different anatomical distribution of the regulatory isoforms may contribute to determine the specificity of diverse cAMP effects. By immunohistochemistry, the distribution of the detergent-insoluble fraction of RIbeta isoform has been examined in rat and mouse brain. Biochemical fractionation shows that a large fraction of both RIalpha and RIbeta isoforms is bound to the cytoskeleton. RIbeta labelling can be observed only in few locations: Purkinje cells, olfactory mitral cells, lateral thalamic neurons, superior olivary complex neurons. These cell populations are involved in the so called Purkinje cell degeneration. On the other hand, RIalpha aggregates have a more widespread distribution, in brain areas involved in visceroemotional control. At the subcellular level, these two subunits show a different pattern of labelling: in most cells a sharply defined clustered labelling is observed for RIalpha isoforms, while the RIbeta isoform presents a weaker, diffuse intracytoplasmic distribution. Competition experiments point to the presence of, as yet unidentified, different and selective anchoring proteins for the two similar RIalpha and beta isoforms. It is suggested that, as is the case for structural proteins, a different supramolecular organization of similar regulatory proteins may be crucial in order to fulfill different functions.

[Effects of high dietary zinc on mice (II)--Influence on growth, blood composition and immune function].

The effects of high-dietary-zinc (HZ, 1.5 g/kg) on growth, blood composition and immune function were studied with a high-dietary-zinc model of mice. By 3 weeks, the body weight and food consumption of mice were significantly lower in HZ group than those in control group. The concentrations of hemoglobin and blood calcium decreased significantly and the platelet and cholesterol levels increased significantly in HZ group. The HZ group showed a spleen swelling and depressed immune function.