Showing papers on "Zinc toxicity published in 2015"

Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.

Abstract: Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways.

Survival in amoeba: a major selection pressure on the presence of bacterial copper and zinc resistance determinants?: identification of a "copper pathogenicity island"

Abstract: The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs.

Roles of some nitrogenous compounds protectors in the resistance to zinc toxicity in Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco

Abstract: Zinc (Zn) pollution in the soil represents a major problem for crop production worldwide. In the present work, two horticultural plants exhibiting different tolerance to Zn, Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco, were exposed to Zn to evaluate the contribution of compatible osmolytes such as proline (Pro), glycine betaine (GB) and γ-aminobutyric acid (GABA) in the mechanism(s) of tolerance to Zn stress. This study confirms the higher susceptibility of L. sativa to Zn stress: lettuce plants experienced a strong reduction in biomass, while the levels of Pro and GB increased. These results suggest that in L. sativa, the increase of Pro and GB does not represent a mechanism of resistance to toxicity, but it is likely a symptom of Zn stress. Conversely, in B. oleracea, a slight decrease in Pro levels, mainly catalysed by degradation through proline dehydrogenase, was observed; a similar behaviour affected GB levels. On the other hand, GABA synthesis was slightly, but significantly, increased. The presence of high levels of GABA in Zn-stressed B. oleracea would suggest that reactive oxygen species detoxification could be essential to improve the resistance to toxicity under metal stress conditions.

Coordinated Zinc Homeostasis Is Essential for the Wild-Type Virulence of Brucella abortus

Abstract: Metal homeostasis in bacterial cells is a highly regulated process requiring intricately coordinated import and export, as well as precise sensing of intracellular metal concentrations. The uptake of zinc (Zn) has been linked to the virulence of Brucella abortus; however, the capacity of Brucella strains to sense Zn levels and subsequently coordinate Zn homeostasis has not been described. Here, we show that expression of the genes encoding the zinc uptake system ZnuABC is negatively regulated by the Zn-sensing Fur family transcriptional regulator, Zur, by direct interactions between Zur and the promoter region of znuABC. Moreover, the MerR-type regulator, ZntR, controls the expression of the gene encoding the Zn exporter ZntA by binding directly to its promoter. Deletion of zur or zntR alone did not result in increased zinc toxicity in the corresponding mutants; however, deletion of zntA led to increased sensitivity to Zn but not to other metals, such as Cu and Ni, suggesting that ZntA is a Zn-specific exporter. Strikingly, deletion of zntR resulted in significant attenuation of B. abortus in a mouse model of chronic infection, and subsequent experiments revealed that overexpression of zntA in the zntR mutant is the molecular basis for its decreased virulence. IMPORTANCE The importance of zinc uptake for Brucella pathogenesis has been demonstrated previously, but to date, there has been no description of how overall zinc homeostasis is maintained and genetically controlled in the brucellae. The present work defines the predominant zinc export system, as well as the key genetic regulators of both zinc uptake and export in Brucella abortus. Moreover, the data show the importance of precise coordination of the zinc homeostasis systems as disregulation of some elements of these systems leads to the attenuation of Brucella virulence in a mouse model. Overall, this study advances our understanding of the essential role of zinc in the pathogenesis of intracellular bacteria.

Local Anesthetic Lidocaine Inhibits TRPM7 Current and TRPM7‐Mediated Zinc Toxicity

Abstract: Summary Background Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn2+ accumulation may represent a promising strategy in the treatment of stroke. Aims To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. Methods Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn2+ imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn2+ accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. Results (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn2+ accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn2+ toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. Conclusion Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity.

Chapter 61 – Zinc

Abstract: Zinc (Zn) is ubiquitous, essential for life, and toxic in excess. When diets provide adequate amounts of bioavailable Zn and intakes of other nutrients are also adequate homeostasis is maintained. When the consumption of bioavailable Zn is insufficient, the risk of deficiency increases. The worldwide prevalence of this phenomenon is at least 20%. Excessive consumption of bioavailable Zn and of exposure to Zn-containing chemicals increase the risk of toxicity. The prevalence of the former is unknown. The latter typically occurs in association with industry; the likelihood is decreased by the use of appropriate precautions. Low available Zn in soil is common and if unmitigated decreases agricultural production. Populations at risk of Zn deficiency are also at risk of other deficiencies. Diets based on cereal and legume products are rich in phytate and other indigestible zinc-binding ligands, and diets based on plant products that are low in Zn, such as roots, tubers, and highly milled rice, are the major causes of human Zn deficiency. Although Zn in animal flesh is highly bioavailable, indigestible Zn-binding ligands in diets suppress its availability. The physiological consequences of Zn deficiency involve all systems. Zinc toxicity is most common after habitual excessive consumption of Zn-containing dietary supplements. Bioavailability of dietary copper (Cu) is suppressed, resulting in deficiency. Inadvertent consumption of Zn-rich dental products over time, and the chronic pica of articles composed of Zn also cause Cu deficiency. Acute gastrointestinal illness can occur after consumption of Zn-contaminated food or drink. Zinc toxicity associated with industry includes flu-like metal fume fever from inhalation of Zn oxide fume. Exposure to highly toxic Zn chloride fume can occur in industry, and from the use of smoke bombs for crowd control.

Phytoremediation potential of moso bamboo (Phyllostachys pubescens) for zinc and ultrastructure changes under zinc toxicity

Abstract: This study has investigated toxicity of Zn and phytoremediation ability in shoot of moso bamboo. In hydroponic experiment the plants showed high Zn torelence up to application of 400 µM, while there was a general trend of decline in the roots and shoot biomass. Maximum concentration of 1594 mg kg–1 was observed in shoot after treating with 100 µM Zn. The shoot/root ratio reached the level of 0.27 under 10 µM zinc stress. Transmission electron microscopy revealed that electron-dense granules in vacuoles and structure of leaf cells were significantly effected by 200 µM of Zn. However, mitochondria and thylakoid membrane arrangement did not alter. Using scanning electron microscopy, Zn-related changes in the structure of the stoma were uncovered and crystal particles probably of Zinc were observed in stem.

Crosstalk between Zinc Status and Giardia Infection: A New Approach.

Abstract: Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia.

Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo

Abstract: A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.

Local and systemic effects of targeted zinc redistribution in Drosophila neuronal and gastrointestinal tissues.

Abstract: While the effects of systemic zinc ion deficiency and toxicity on animal health are well documented, the impacts of localized, tissue-specific disturbances in zinc homeostasis are less well understood. Previously we have identified zinc dyshomeostasis scenarios caused by the targeted manipulation of zinc transport genes in the Drosophila eye. Over expression of the uptake transporter dZIP42C.1 (dZIP1) combined with knockdown of the efflux transporter dZNT63C (dZNT1) causes a zinc toxicity phenotype, as does over expression of dZIP71B or dZNT86D. However, all three genotypes result in different morphologies, responses to dietary zinc, and genetic interactions with the remaining zinc transport genes, indicating that each causes a different redistribution of zinc within affected cells. dZNT86D (eGFP) over expression generates a completely different phenotype, interpreted as a Golgi zinc deficiency. Here we assess the effect of each of these transgenes when targeted to a range of Drosophila tissues. We find that dZIP71B is a particularly potent zinc uptake gene, causing early developmental lethality when targeted to multiple different tissue types. dZNT86D over expression (Golgi-only zinc toxicity) is less deleterious, but causes highly penetrant adult cuticle, sensory bristle and wing expansion defects. The dZIP42C.1 over expression, dZNT63C knockdown combination causes only moderate adult cuticle defects and sensitivity to dietary zinc when expressed in the midgut. The Golgi-only zinc deficiency caused by dZNT86D (eGFP) expression results in mild cuticle defects, highly penetrant wing expansion defects and developmental lethality when targeted to the central nervous system and, uniquely, the fat bodies.

Acute Cadmium Exposure Reduces the Local Angiotensin I Converting Enzyme Activity and Increases the Tissue Metal Content.

Abstract: Cadmium exposure causes health problems that may result from increased oxidative stress and from changes in enzyme metalloproteases activities as angiotensin-converting enzyme (ACE). In fact, cadmium produces inhibition of serum ACE but is not known how cadmium acts on tissue ACE activity and whether following acute exposure tissue cadmium content is increased. In order to elucidate these issues, a cadmium bolus was injected intravenously in Wistar rats, and the cadmium content and the ACE activity were measured in the serum, lungs, aorta and kidneys. Moreover, in order to clarify if the cadmium affects directly tissue ACE activity, acute metal exposure in vitro was performed. Our results demonstrated that 120 min following cadmium administration, blood and organ cadmium content were both increased. Serum and lung ACE activity were reduced following acute cadmium exposure, but aortic and kidney ACE activities were not affected. The inhibitory effects induced by cadmium on ACE activity were also observed in the serum, as well as the lungs and the aorta, but not in the kidneys following in vitro exposure. Moreover, the inhibitory effects induced by cadmium on ACE activity were partially restored in vitro by zinc supplementation, suggesting a possible interaction or competition between cadmium and zinc by at the active site of ACE. Summarising, our results suggest that acute cadmium exposure promotes an increase in the tissue metal content that was accompanied by direct inhibition of serum, aorta and lung ACE activity, an effect that is cadmium concentration-dependent and is partially reversed by zinc.

Influence of water quality on zinc toxicity to the Florida apple snail (Pomacea paludosa) and sensitivity of freshwater snails to zinc

Abstract: The present study characterized the influence of water-quality characteristics on zinc (Zn) toxicity to the Florida apple snail (Pomacea paludosa) and the sensitivity of freshwater snails to Zn. Standard 96-h renewal acute toxicity tests were conducted with Zn and juvenile P. paludosa under 3 conditions of pH and alkalinity, water hardness, and dissolved organic carbon (DOC). Median lethal effect concentrations (96-h LC50s), no-observed- effect concentrations, lowest-observed-effect concentrations, LC10s, and LC20s were determined for each test. The results showed that Zn toxicity to P. paludosa decreased linearly with increasing hardness, pH, and DOC. A multiple linear regression model based on pH, hardness, and DOC was able to explain 99% of the observed variability in LC50s. These results are useful for the development of a biotic ligand model (BLM) for P. paludosa and Zn. Zinc acute toxicity data were collected from the literature for 12 freshwater snail species in a wide range of water-quality characteristics for species sensitivity distribution analysis. The results showed that P. paludosa is the second most sensitive to Zn. The present study also suggested that aqueous ZnCO3 and ZnHCO3 (-) can be bioavailable to P. paludosa. Therefore, bioavailability models (e.g., BLM) should take these Zn species into consideration for bioavailability when applied to snails.

The potentiation of zinc toxicity by soil moisture in a boreal forest ecosystem.

Abstract: Northern boreal forests often experience forest dieback as a result of metal ore mining and smelting. The common solution is to lime the soil, which increases pH, reducing metal toxicity and encouraging recovery. In certain situations, however, such as in Flin Flon, Manitoba, Canada, liming has yielded only moderate benefits, with some locations responding well to liming and other locations not at all. In an effort to increase the effectiveness of the ecorestoration strategy, the authors investigated if these differences in liming responsiveness were linked to differences in toxicity. Toxicity of metal-impacted Flin Flon soils on the oribatid mite Oppia nitens and the collembolan Folsomia candida was assessed, with a view toward identifying the metal of concern in the area. The effects of moisture content on metal sorption, uptake, and toxicity to the invertebrates were also investigated. Toxicity tests with the invertebrates were conducted using either Flin Flon soils or artificial soils with moisture content adjusted to 30%, 45%, 60%, or 75% of the maximum water-holding capacity of the soil samples. The Relative to Cd Toxicity Model identified Zn as the metal of concern in the area, and this was confirmed using validation tests with field contaminated soils. Furthermore, increasing the moisture content in soils increased the amount of mobile Zn available for uptake with the ion exchange resin. Survival and reproduction of both invertebrates were reduced under Zn exposure as moisture level increased. Thus, moisture-collecting landforms, which are often also associated with high Zn concentrations at Flin Flon, have, as a result, higher Zn toxicity to the soil ecosystem because of increases in soil moisture. Environ Toxicol Chem 2015;34:600–607. © 2014 SETAC

Impaired behavior and changes in some biochemical markers of bivalve (Ruditapes decussatus) due to zinc toxicity

Abstract: Susceptibility and response of bivalves, the clam Ruditapes decussatus, to zinc (Zn) were studied by monitoring behavior using valve movement and some biochemical parameters. The LC50 was 4.1 mg L−1 at 7 days. Depuration of Zn from their tissues was also followed. Accumulation of Zn increased with concentration and duration of exposure. After 20 days, Zn caused impairment of valve movement as well as the antioxidant system, decreasing glutathione and protein levels and increasing the lipid peroxidation which is indicative of oxidative damage. Results suggested that behavior and biochemical parameters of clam R. decussatus were sensitive and suitable responses for assessing the effects of Zn on the aquatic ecosystems. It could be concluded that there is a time–dose–response relationship of Zn with behavior and oxidative stress of R. decussatus.

The Effects of Chronological Age and Size on Toxicity of Zinc to Juvenile Brown Trout

Abstract: A series of toxicity tests were conducted to investigate the role of chronological age on zinc tolerance in juvenile brown trout (Salmo trutta). Four different incubation temperatures were used to control the maturation of the juveniles before zinc exposures. These 96-h exposures used flow-through conditions and four chronological ages of fish with weights ranging from 0.148 to 1.432 g. Time-to-death (TTD) data were collected throughout the exposure along with the final mortality. The results indicate that chronological age does not play a predictable role in zinc tolerance for juvenile brown trout. However, a relationship between zinc tolerance and fish size was observed in all chronological age populations, which prompted us to conduct additional exploratory data analysis to quantify how much of an effect size had during this stage of development. The smallest fish (0.148–0.423 g) were shown to be less sensitive than the largest fish (0.639–1.432 g) with LC50 values of 868 and 354 µg Zn/L, respectively. The Kaplan–Meier product estimation method was used to determine survival functions from the TTD data and supports the LC50 results with a greater median TTD for smaller fish than larger juvenile fish. These results indicate that fish size or a related characteristic may be a significant determinant of susceptibility and should be considered in acute zinc toxicity tests with specific attention paid to the expected exposure scenario in the field.

Acidosis and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) Attenuate Zinc/Kainate Toxicity in Cultured Cerebellar Granule Neurons.

Abstract: Cultured cerebellar granule neurons (CGNs) are resistant to the toxic effect of ZnCl2 (0.005 mM, 3 h) and slightly sensitive to the effect of kainate (0.1 mM, 3 h). Simultaneous treatment of CGNs with kainate and ZnCl2 caused intensive neuronal death, which was attenuated by external acidosis (pH 6.5) or 5-(N-ethyl-N-isopropyl)amiloride (EIPA, Na+/H+ exchange blocker, 0.03 mM). Intracellular zinc and calcium ion concentrations ([Zn2+]i and [Ca2+]i) were increased under the toxic action of kainate + ZnCl2, this effect being significantly decreased on external acidosis and increased in case of EIPA addition. Neuronal Zn2+ imaging demonstrated that EIPA increases the cytosolic concentration of free Zn2+ on incubation in Zn2+-containing solution. These data imply that acidosis reduces ZnCl2/kainate toxic effects by decreasing Zn2+ entry into neurons, and EIPA prevents zinc stores from being overloaded with zinc.

Exogenous Salicylic Acid Alleviates Zinc-induced Oxidative Damage in Tomato Plants

Abstract: In the present study, the effects of Zinc (Zn) and salicylic acid (SA) interaction on tomato plants were examined. 25-day-old tomato plants were subjected to different concentrations of ZnSO4 . 7H2O (0, 250, 500 µM) and SA (0, 100 µM) for 10 days. Zn was accumulated in roots and shoots of Zn-stressed plants. Treatment with Zn reduced dry weight of roots and shoots and decreased chlorophyll content in leaves. In Zn-treated plants, Malondialdehyde (MDA), H2O2 and proline contents significantly increased in leaves. Moreover, changes in the activities of the antioxidant enzymes, catalase, guaiacol peroxidase, ascorbate peroxidase and superoxide dismutase in leaves indicated that Zn caused an oxidative stress in tomato plants. In Zn-stressed plants, application of SA reduced root-to-shoot translocation of Zn and enhanced growth and chlorophyll content. Adding of SA in the nutrient solution, increased the antioxidant enzymes activities and decreased the level of lipid peroxidation, H2O2 and proline accumulation in leaves of Zn-treated plants. As a result, SA by sequestration of Zn in roots and increase in the activities of antioxidant enzymes, considerably decreased Zn induced oxidative damage on tomato plants