Showing papers on "Zinc toxicity published in 2021"

Frontline Science: LPS-inducible SLC30A1 drives human macrophage-mediated zinc toxicity against intracellular Escherichia coli

Abstract: TLR-inducible zinc toxicity is an antimicrobial mechanism utilized by macrophages, however knowledge of molecular mechanisms mediating this response is limited. Here, we show that E. coli exposed to zinc stress within primary human macrophages reside in membrane-bound vesicular compartments. Since SLC30A zinc exporters can deliver zinc into the lumen of vesicles, we examined LPS-regulated mRNA expression of Slc30a/SLC30A family members in primary mouse and human macrophages. A number of these transporters were dynamically regulated in both cell populations. In human monocyte-derived macrophages, LPS strongly up-regulated SLC30A1 mRNA and protein expression. In contrast, SLC30A1 was not LPS-inducible in macrophage-like PMA-differentiated THP-1 cells. We therefore ectopically expressed SLC30A1 in these cells, finding that this was sufficient to promote zinc-containing vesicle formation. The response was similar to that observed following LPS stimulation. Ectopically expressed SLC30A1 localized to both the plasma membrane and intracellular zinc-containing vesicles within LPS-stimulated THP-1 cells. Inducible overexpression of SLC30A1 in THP-1 cells infected with the Escherichia coli K-12 strain MG1655 augmented the zinc stress response of intracellular bacteria and promoted clearance. Furthermore, in THP-1 cells infected with an MG1655 zinc stress reporter strain, all bacteria contained within SLC30A1-positive compartments were subjected to zinc stress. Thus, SLC30A1 marks zinc-containing compartments associated with TLR-inducible zinc toxicity in human macrophages, and its ectopic over-expression is sufficient to initiate this antimicrobial pathway in these cells. Finally, SLC30A1 silencing did not compromise E. coli clearance by primary human macrophages, suggesting that other zinc exporters may also contribute to the zinc toxicity response.

An alloy of zinc and innate immunity: Galvanising host defence against infection.

Abstract: Innate immune cells such as macrophages and neutrophils initiate protective inflammatory responses and engage antimicrobial responses to provide frontline defence against invading pathogens. These cells can both restrict the availability of certain transition metals that are essential for microbial growth and direct toxic concentrations of metals towards pathogens as antimicrobial responses. Zinc is important for the structure and function of many proteins, however excess zinc can be cytotoxic. In recent years, several studies have revealed that innate immune cells can deliver toxic concentrations of zinc to intracellular pathogens. In this review, we discuss the importance of zinc status during infectious disease and the evidence for zinc intoxication as an innate immune antimicrobial response. Evidence for pathogen subversion of this response is also examined. The likely mechanisms, including the involvement of specific zinc transporters, that facilitate delivery of zinc by innate immune cells for metal ion poisoning of pathogens are also considered. Precise mechanisms by which excess levels of zinc can be toxic to microorganisms are then discussed, particularly in the context of synergy with other antimicrobial responses. Finally, we highlight key unanswered questions in this emerging field, which may offer new opportunities for exploiting innate immune responses for anti‐infective development.

The Influence of pH on Zinc Lability and Toxicity to a Tropical Freshwater Microalga.

Abstract: Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity-modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc (Zn) to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration, and diffusive gradients in thin films (DGT). Zinc toxicity increased significantly with increasing pH from 6.7 to 8.3, with 50% growth inhibition effect concentrations decreasing from 185 to 53 µg l-1 across the pH range. Linear relationships between DGT-labile Zn and dissolved Zn did not vary across the tested pH range, nor did the linear relationship between dissolved (<0.45 µm) and ultrafiltered (<3 kDa) Zn. Our findings show that Zn toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and that these toxicity changes could not be explained by Zn speciation and lability as measured by DGT and WHAM7. Environ Toxicol Chem 2021;40:2836-2845. © 2021 SETAC.

Bioaccumulation and transfer of zinc in soil plant and animal system: a health risk assessment for the grazing animals

Abstract: Heavy metals pollution has thorough worldwide apprehensions due to the instantaneous growth of industries. Farming regions are irrigated mainly with wastewater which contains both municipal and industrial emancipations. Keeping in view the above scenario, a study was designed in which three sites irrigated with ground, canal, and municipal wastewater in the District Jhang were selected to determine the zinc accumulation and its transfer in the soil, plant, and animal food chain. Zinc concentration was ranged as 18.85–35.59mg/kg in the soil, 26.42–42.67 mg/kg in the forage, and 0.982–2.85mg/kg in the animal samples. Investigated zinc concentration in soil and forages was found to be within the recommended WHO/FAO limits, but blood samples exceed the standards of NRC (2007). The maximum level of pollution load index (0.427–0.805mg/kg) and enrichment factor (0.373–0.894 mg/kg) for zinc was noticed upon wastewater irrigation. Daily intake (0.039 to 0.082 mg/kg/day) and health risk index (0.130 to 0.275 mg/kg/day) of zinc metal was higher in the buffaloes that feed on wastewater-irrigated forages. Bio-concentration factor (0.840 to 2.01mg/kg) for soil-forage was >1 which represents that these plants accumulated the zinc concentration into their tissues and raised health issues in grazing animals on consumption of wastewater-contaminated forages. As animal-derived products are part of human food, then zinc toxicity prevailed in livestock tissues ultimately affects the human food chain. Overall, findings of this study concluded that animal herds should be monitored periodically to devise preventive measures regarding the toxic level of heavy metals availability to livestock.

Erythropoietin-Resistant Anemia Secondary to Zinc-Induced Hypocupremia in a Hemodialysis Patient.

Abstract: Excessive intake of zinc is a known but often forgotten cause of copper deficiency, and its consequences in the context of end-stage renal disease (ESRD) are not widely discussed. Zinc-induced copper deficiency (ZICD) can result in erythropoietin (EPO)-resistant anemia and may not be considered as a possible etiology when conducting the work-up. We present a case wherein an ESRD patient had been receiving excess zinc for several months and subsequently experienced EPO-resistant anemia. Our patient's GI work-up was negative, and increased doses of iron and EPO-stimulating agent were ineffective. She underwent a bone marrow biopsy and more serological testing. She was ultimately diagnosed with ZICD, and cessation of her zinc supplement and initiation of copper replacement proved effective in restoring EPO responsiveness. Awareness of ZICD as a possible factor in EPO-resistant anemia could lead to an expedited diagnosis and avoid an unnecessary and extensive work-up.

Silicon distribution in leaves and roots of rice and maize in response to cadmium and zinc toxicity and the associated histological variations.

Abstract: At present, the levels of cadmium (Cd) and zinc (Zn) in arable land are high and affect the growth and development of important food crops, including rice and maize. However, the application of silicon (Si) in contaminated areas increases the metal tolerance potential of these plants. This work aimed to study the variations in the distribution pattern of endogenous Si in various tissue regions in roots and leaves of rice and maize exposed to cadmium (Cd) and zinc (Zn) stresses. For these experiments, 45 day-old rice (var. Varsha) and maize (var. CoHM6) seedlings were treated with 1.95 g Zn and 0.45 g Cd kg-1 soil. Under Cd stress, the distribution of Si was high in the cortical region of the root, but under Zn stress, the highest Si deposition was found in the endodermis. In leaves, Si deposition was high in both the mesodermis and stelar regions of Cd-treated plants but more Si was deposited in the mesodermis tissue of Zn-treated plants. Heavy metal (Cd and Zn) accumulation and Si deposition showed a strong negative correlation in the roots of rice and maize plants. Complexation with metal ions and redistribution of Si were considered the major mechanisms in Si-mediated mitigation of Cd and Zn stress. Cd- and Zn-induced anatomical changes, such as endodermal thickening, deposits in the xylary elements and aerenchyma formation in the roots of rice and maize, were also associated with the Si distribution.

Influence of salinity on physiological development and zinc toxicity in the marine medaka Oryzias melastigma

Abstract: To determine whether the marine medaka Oryzias melastigma is a suitable model organism for evaluating the effects of environmental chemicals on marine teleosts, we examined the effect of salinity on physiological development and zinc toxicity. Growth as measured by total body length was significantly lower in fresh water compared to brackish water. Reproductive success was also significantly reduced in fresh water, although we observed cells in the pituitary producing gonadotropins such as Gpa (common glycoprotein hormone α), Fshb (follicle stimulating hormone β), and Lhb (luteinizing hormone β) at all salinities. These results indicate that O. melastigma is adaptable to various salinities from fresh to seawater, and brackish water is best for physiological processes including growth performance and reproduction. When zinc was dissolved in saltwater, a white precipitate formed immediately, and the dissolved concentration decreased in the supernatant and increased at precipitate. We performed zinc toxicity tests on early life stage and adult stage in fresh water, brackish water, and seawater. Among adults, the lowest observed effect concentration for mortality in freshwater (15.3 mg/L) was lower than in brackish water (>48 mg/L) or seawater (>48 mg/L). Similarly, among embryos and larvae, the lowest observed effect concentration for mortality in freshwater (4.8 mg/L) was lower than in brackish water (48 mg/L) or seawater (48 mg/L). These results highlight the importance of using marine organisms to evaluate the ecological effects of marine pollutants.

Suspected hemolytic anemia secondary to acute zinc toxicity after ingestion of "max strength" (zinc oxide) diaper rash cream.

Abstract: OBJECTIVE To describe the clinical presentation of a dog with hemolytic anemia secondary to zinc toxicosis after 1-week use of "max strength" 40% diaper rash cream. CASE SUMMARY A 2-year-old female neutered Maltese presented for vomiting, lethargy, pigmenturia, and pale mucous membranes. "Max Strength" zinc oxide cream had been applied to the patient daily for a week prior to presentation. Clinical examination revealed light pink to pale mucous membranes and tachycardia. Hematology demonstrated large numbers of spherocytes and a strongly regenerative anemia. Plasma zinc concentrations were markedly increased. A diagnosis of hemolytic anemia secondary to subacute zinc toxicosis was made and supportive therapy was instigated. The patient ultimately recovered uneventfully. Acute or subacute zinc toxicosis resulting in hemolytic anemia is not frequently observed, and this case was also unusual in that the zinc source was diaper cream, which historically has been thought to require very large quantities to cause toxicosis. NEW OR UNIQUE INFORMATION PROVIDED To the authors' knowledge, there is only one previously reported case of hemolytic anemia secondary to diaper cream use in a hospital setting but no previous reports involving toxicosis secondary to prolonged application at home by owners. Most commercial diaper creams contain zinc oxide, which historically was thought to have poor gastrointestinal absorption and would require a large quantity to cause significant toxicosis and hemolytic anemia. Moreover, this case emphasizes the potential risks associated with zinc oxide cream use, the significance of client education if using these creams, as well as the importance of history in elucidating the underlying cause of hemolytic anemia.

Effects of zinc toxicity on the nitrogen-fixing cyanobacterium Anabaena sphaerica-ultastructural, physiological and biochemical analyses.

Abstract: The current study describes the mechanisms of zinc toxicity in the cyanobacterium Anabaena sphaerica after eight days treatment with 10 mg L−1 ZnCl2. The application of zinc not only showed elevated accumulation of the metal inside the cells but also exhibited devastating impacts on the cell numbers, morphology, and ultrastructure of A. sphaerica. The effects of zinc on the pigments contents, oxygen evolution rate, Fv/Fm, electron transport rate, and carbohydrate content were also evaluated in A. sphaerica. Moreover, zinc adversely affected nutrient uptake and the cellular energy budget in the test cyanobacterium which in turn hampered heterocyst development and nitrogen fixation. Alongside, the cyanobacterium experienced zinc-mediated non-competitive inhibition of glutamine synthetase activity, curtailed synthesis of amino acids and proteins. Furthermore, drastically reduced total lipid and increased unsaturated lipid contents were also the prominent characteristics of zinc stressed A. sphaerica. Most importantly, zinc stress caused severe damages to the protein, lipid, and DNA by triggering hydrogen peroxide generation and accumulation of oxidized glutathione. Therefore, excess zinc is highly toxic to the cyanobacterium A. sphaerica, and the mechanisms of its toxicity followed a cascade of events including oxidative stress mediated geopardisation of growth and ultrastructure, metabolic derangements, and macromolecular damages.

Antimicrobial zinc toxicity in Mϕs: ZnT1 pays the toll

Abstract: Transition metals, including zinc, are essential to all living organisms. They are also toxic in high amounts, and their intracellular concentration must be tightly regulated. In this edition of JLB, Stocks et al. report that the zinc transporter, ZnT1 (SLC30A1) is induced by TLR4 activation in Mϕs, in which it contributes to zinc accumulation in Escherichia coli-containing phagosomes, resulting in increased bacterial clearance.

Zing thing about zinc: A mini review

Abstract: Zinc is a micromineral present in the body tissues and fluids. Zinc is absorbed from the duodenum and stored in the form of metallothionine in the liver and excreted through sweat. Zinc plays a vital role in protein biosynthesis, gene expression; it also acts as an antioxidant and is used in the growth of the fungus. Due to the deficiency of zinc, a patient will be suffering from poor wound healing, lesions of skin, impaired spermatogenesis, hyperkeratosis, dermatitis and alopecia.An unprecedented COVID-19 pandemic caused by a novel corona virus called SARS-CoV-2, produces severe acute respiratory distress syndrome (ARDS). Zinc is used to treat COVID 19 because it improves the immunity. As the COVID patients are susceptible to zinc deficiency, they are prescribed with zinc supplements. Intake of zinc more than1000mg/day causes Zinc toxicity. Fungus utilises zinc for its growth. Mucormycosis caused by fungus Rhizopus species seen in most of the post COVID patients. Since, Zinc has assumed importance in this COVID 19 pandemic, this review article unfathoms the explicit roles of Zinc in humans. Keywords: COVID 19, Mucormycosis, Zinc, Zinc toxicity.