Zinc glycinate alleviates LPS-induced inflammation and intestinal barrier disruption in chicken embryos by regulating zinc homeostasis and TLR4/NF-κB pathway.

The effect of an immune challenge induced by a lipopolysaccharide (LPS) exposure on systemic zinc homeostasis and the modulation of zinc glycinate (Zn-Gly) was investigated using a chicken embryo model. 160 Arbor Acres broiler fertilized eggs were randomly divided into 4 groups: CON (control group, injected with saline), LPS (LPS group, injected with 32 µg of LPS saline solution), Zn-Gly (zinc glycinate group, injected with 80 µg of zinc glycinate saline solution) and Zn-Gly+LPS (zinc glycinate and LPS group, injected with the same content of zinc glycinate and LPS saline solution). Each treatment consisted of eight replicates of five eggs each. An in ovo feeding procedure was performed at 17.5 embryonic day and samples were collected after 12 hours. The results showed that Zn-Gly attenuated the effects of LPS challenge-induced upregulation of pro-inflammatory factor interleukin 1ß (IL-1ß) level (P =0.003). The LPS challenge mediated zinc transporter proteins and metallothionein (MT) to regulate systemic zinc homeostasis, with increased expression of the jejunum zinc export gene zinc transporter protein 1 (ZnT-1) and elevated expression of the import genes divalent metal transporter 1 (DMT1), Zrt- and Irt-like protein 3 (Zip3), Zip8 and Zip14 (P < 0.05). A similar trend could be observed for the zinc transporter genes in the liver, which for ZnT-1 mitigated by Zn-Gly supplementation (P =0.01). Liver MT gene expression was downregulated in response to the LPS challenge (P =0.004). These alterations caused by LPS resulted in decreased serum and liver zinc levels and increased small intestinal, muscle and tibial zinc levels. Zn-Gly reversed the elevated expression of the liver zinc finger protein A20 induced by the LPS challenge (P =0.025), while Zn-Gly reduced the gene expression of the pro-inflammatory factors IL-1ß and IL-6, decreased toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) (P < 0.05). Zn-Gly also alleviated the LPS-induced downregulation of the intestinal barrier gene Claudin-1. Thus, LPS exposure prompted the mobilization of zinc transporter proteins and MT to perform the remodeling of systemic zinc homeostasis, Zn-Gly participated in the regulation of zinc homeostasis and inhibited the production of pro-inflammatory factors through the TLR4/NF-κB pathway, attenuating the inflammatory response and intestinal barrier damage caused by an immune challenge.

Determination of the median lethal dose of zinc gluconate in mice and safety evaluation.

BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.

Zinc deficiency induced by the chelating agent DTPA and its regulatory interpretation for developmental toxicity classification.

Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the European Union as a developmental toxicant CLP Category 1B. However, according to the CLP regulation (CLP, 2008) classification as a developmental toxicant requires a chemical to possess an intrinsic, specific property to do so. This paper provides overwhelming evidence that shows the developmental toxicity only seen at a sustained high dose of 1000 mg DTPA/kg bw/day in rats during pregnancy is mediated by zinc depletion which leads to non-specific secondary effects associated with zinc deficiency. Therefore, based on the CLP regulation itself, viz. the lack of a specific, intrinsic property, supported by significant differences in zinc kinetics and physiology between pregnant rats and pregnant women, DTPA should not be classified as a developmental toxicant. Moreover, classification for developmental toxicity resulting from zinc deficiency, and only observed at high doses, would not increase protection of human health; instead, it will only lead to onerous and disproportionate restrictions being placed on the use of this substance.

A trait-based approach to determine the risks of Zn to the overall health status of native fish species Barbus meridionalis.

Fish adapt to changing environments by maintaining homeostasis or making energy trade-offs that impact fitness. We investigated the effect of Zn on the fitness and physiology of Barbus meridionalis, a native cyprinid fish species, under two exposure scenarios. The Osor stream's mine-effluent reach represented long-term (chronic) exposure, while the upstream reach served as a control/acute exposure. Acute exposure involved exposing B. meridionalis to 1mg/L Zn for 96 h in the laboratory. We examined physiological traits (Standard metabolic rate SMR, Maximum metabolic rate MMR, Absolute Aerobic scope AAS, Critical swimming capacity Ucrit) and antioxidant system, AS (Superoxide dismutase, SOD; Catalase, CAT; Glutathione peroxidase, GPX; Glutathione-S-transferase, GST; Glutathione, GSH; Thiobarbaturic acid reactive substances, TBARS) biomarkers. The results indicated that Zn had no significant effect on osmoregulatory cost (SMR) in either exposure scenario but impaired energetically costly exercise (low MMR). AAS reduction in both exposure groups suggested compromised energy allocation for life-history traits, evidenced by decreased locomotor performance (Ucrit) after acute exposure. Tissue-specific and time-dependent responses were observed for AS biomarkers. The fish exhibited ineffective control of oxidative damage, as evidenced by high TBARS levels in the liver and gills, despite increased CAT and GSH in the liver under acute conditions. Our findings demonstrate differential responses at the subcellular level between the two exposure scenarios, while trait-based endpoints followed a similar pattern. This highlights the utility of a trait-based approach as a supplementary endpoint in biomonitoring studies, which provides insights into impacts on individual fitness and population demography.

Effects of zinc supplementation in mitigating the harmful effects of chronic cadmium exposure in a zebrafish model.

Cadmium (Cd) is a heavy metal that is highly toxic to living organisms, including humans. But the dietary zinc (Zn) supplements play critical role in minimizing or preventing Cd poisoning, without any side effects. The underlying mechanisms, however, have not been thoroughly investigated. Therefore, in this study, we investigated the use of Zn as a protection against Cd toxicity in zebrafish models. The obtained results confirmed the levels of antioxidant enzymes and supported the synergistic effects of Zn in reducing Cd toxicity. The lipid, carbohydrate, and protein concentrations in the liver tissue have also been negatively impacted by Cd; however, treatment with Zn has lessened these adverse effects. Furthermore, the level of 8-hydroxy-2' -deoxyguanosine (8-OHdG), caspase-3 also confirms the protective effects of Zn in reducing DNA damage caused by Cd. The results of this study demonstrate that a Zn supplement can lessen the harmful effects of Cd in zebrafish model.

An alternative ZnO with large specific surface area: Preparation, physicochemical characterization and effects on growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets.

High-dose ZnO is widely used to prevent diarrhea and promote growth of weaning piglets, which has led to serious problems of animal toxicity, bacterial resistance and environmental pollution. In this study, a novel alternative ZnO (AZO) was prepared and its physicochemical properties were characterized. Animal experiments were further conducted to evaluate the effects of the ZnO forms, the dose of AZO and the combinations with AZO on the growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets. The results showed that the AZO, compared with ordinary ZnO (OZO), nano ZnO (NZO) and porous ZnO (PZO), had the largest surface area and reduced the release of Zn2+ into the gastric fluid. AZO showed better antibacterial activity on Escherichia coli K88, Staphylococcus aureus and Salmonella enteritidis but lower cytotoxicity on porcine intestinal epithelial cells. Animal experiments suggested that low-dose AZO, NZO and PZO (300 mg/kg) improved growth performance and reduced diarrhea in weaning piglets as well as high-dose OZO (3000 mg/kg). Notably, low-dose AZO had the lowest diarrhea incidence. Additionally, low-dose AZO in combination with probiotics improved digestibility and digestive enzyme activities. Low-dose AZO in combination with probiotics also upregulated the expression of the intestinal zinc transporter proteins ZIP4 and DMT1, increased zinc bioavailability, reduced faecal zinc emissions, and avoided zinc overload in the liver and oxidative damage caused by high-dose ZnO. Moreover, low-dose AZO in combination with probiotics improved the gut barrier function of weaning piglets by promoting the expression of tight junction proteins, mucins and antimicrobial peptides and increasing gut microbiota diversity and beneficial Lactobacillus. This study proposed a novel strategy to replace high-dose ZnO and antibiotics with low-dose AZO and probiotics in weaning piglets, which effectively improved growth performance and prevented diarrhea while reducing animal toxicity, bacterial resistance, heavy metal residues and zinc emission pollution.

Four-week repeated oral dose toxicity study of zinc maltol in rats.

Zinc (Zn) is one of the trace elements, and Zn deficiency causes many adverse effects. Zn complexes are used for Zn supplementation, but there are few toxicity reports. Zn maltol (ZM) was orally administered for 4 weeks to male rats at a dose of 0, 200, 600, or 1000 mg/kg to assess its toxicity. As a ligand group, maltol was administered at a dose of 800 mg/kg/day. General conditions, ophthalmology, hematology, blood biochemistry, urinalysis, organ weights, necropsy, histopathology, and plasma Zn concentration were investigated. Plasma Zn concentration increased with dose levels of ZM. The following toxicities were observed at 1000 mg/kg. Pancreatitis was observed with histopathological lesions and increases in white blood cell parameters and creatine kinase. Anemia was observed with changes in red blood cell parameters and extramedullary hematopoiesis in the spleen. Decreases in the trabecula and growth plate in the femur were observed. On the other hand, no toxicities were observed in the ligand group. In conclusion, these toxicities induced by ZM have been reported as Zn-related toxicities. It was considered that these results will be helpful for a creation and development of new Zn complexes as well as supplements.

Different responses to joint exposure to cadmium and zinc depends on the sex in Populus cathayana.

The alarming increase in soil contamination by heavy metals, such as cadmium and zinc demands immediate attention. The dioecious tree Populus cathayana, a phytoremediation plant, plays an important role in rehabilitating heavy metal contaminated areas. In this study, male and female P. cathayana plants were treated with Cd (20 mg kg-1) and different levels of Zn (25, 50, or 100 mg kg-1) to study their physiological responses. The results showed that Cd exposure alone caused stress by inhibiting the growth of both male and female plants. In both males and females, photosynthesis and antioxidant enzymes activities decreased substantially under Cd stress alone. Cd was largely located in the roots, but Zn was present in the shoots of both sexes. Zn supplementation considerably increased the photosynthetic rate from 14.62 % to 60.45 % and also enhanced the antioxidant enzymes activities from 24.11 % to 86.21 %. Zn treatment decreased the translocation ability of Cd compared to the Cd-only treatment, alleviating Cd toxicity. In addition, when sufficient Zn was made available, males showed a high degree of Cd accumulation, low root-to-shoot translocation, elevated antioxidant defense abilities, and an increased photosynthetic rate, while females were less responsive to Cd stress than males. Thus, combined exposure to Cd and Zn caused differential responses in plant growth and physiological processes between males and females P. cathayana. Male plants exhibit better Cd tolerance and accumulation capacity under optimum Zn supplementation. This study increases the fundamental knowledge regarding P. cathayana plants, which can be applied to enhance their remediation capacity in Cd-contaminated soils.

A multipollutant low-grade exposure regulates the expression of miR-30b, Let-7a and miR-223 in maternal sera: Evidence from the NEHO cohort.

There is growing evidence that environmental pollutants can induce epigenetic modifications altering the balance of miRNAs and inducing the onset of pathological conditions in animals. In this study, we measured the serum concentration of a suite of inorganic and organic pollutants (Cu, Zn, Se, Hg, HCB, p,p'-DDE, PCBs) and their association to serum miR-30b, miR-223 and Let-7a microRNA expression in 68 healthy pregnant women from the NEHO birth cohort sited in a highly industrialized area. The effects of the pollutants on the modulation of circulating miRNAs' expression were first investigated using linear continuous regression models with a single-compound approach showing that miR-223 expression was significantly associated with serum concentration of Se and Zn (pSe = 0.0336; pZn = 0.0225) and miR-30b was associated with Hg levels (pHg = 0.019). Furthermore, when contaminants were categorized into tertiles, miR-223 and miR-30b showed a positive association with higher tertiles of Zn, p,p'-DDE (pZn = 0.023; pDDE = 0.041) and Hg (pHg = 0.008), respectively. Moreover, Let-7a expression was exclusively influenced by medium tertiles levels of Se (low vs medium tertiles, p = 0.001). Simultaneous exposure to multi-pollutant mixture was approached by WQS regression model. Statistical analysis shows a driving effect of Zn, Se, Cu, Hg and HCB on significant increased expression of Let-7a (p = 0.045). Mercury and Se significantly amplified the expression for miR-30b (p = 0.038). Differently, the combined effect of p,p'-DDE, Zn and Se decreased miR-223 expression (p = 0.0001). The documented modified expression of circulating miRNAs in the serum of pregnant women, exposed to low-medium dose contaminants mixtures offers innovative early-warning approaches to human health risk assessment.

Use of Generalized Weighted Quantile Sum Regressions of Tumor Necrosis Factor Alpha and Kidney Function to Explore Joint Effects of Multiple Metals in Blood.

Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-α) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-α as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-α in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-α and kidney function. We also approached the relationship between metals/metalloids and TNF-α by generalized additive models (GAM). The relationship of the exposure−response curve between Pb level and TNF-α in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-α levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-α and kidney function. The toxic metal group found significantly positive associations with TNF-α, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-α even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research.

Bio-efficacy of iron and zinc fortified wheat flour along with bio-assessment of its hepatic and renal toxic potential.

Study was planned to assess the bio-efficiency along with toxicity of iron and zinc fortified whole wheat flour in Sprague dawley albino rats. Whole wheat flour was fortified with different dosage of sodium iron EDTA (NaFeEDTA), ferrous sulphate (FeSO4), zinc oxide (ZnO) and zinc sulphate (ZnSO4). The rats (n=3) in each group were fed on fortified wheat flour for 2 months. Liver biomarkers including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin were recorded from serum samples. Increased concentration of ZnSO4 affected the liver biomarkers to be highest among all whereas, bilirubin levels were less than the rats fed on control diet. The above mentioned fortificants have negligible effect on renal biomarkers including creatinine and urea. Moreover, hematological parameters were also checked and reportedly, sodium iron EDTA fed rats presented highest amount of hemoglobin, iron and total iron binding capacity. Highest zinc level was observed in rats fed on whole wheat flour fortified with 60mg/Kg Zinc oxide. Microscopic observation of liver tissue depicted that rats fed on iron and zinc fortified wheat flour have more toxic effects whereas, histopathology presentation of kidney tissue has least toxic impact. It has been concluded that mandatory fortification of wheat flour with iron and zinc may cause increased serum biomarkers along with toxicity of vital organs like liver, hence fraction of wheat flour may be fortified to fulfill the requirements of deprived and vulnerable group.

Multi-omics reveals the regulatory mechanisms of zinc exposure on the intestine-liver axis of golden pompano Trachinotus ovatus.

Metal zinc (Zn) has been the focus of many environmental toxicological studies, but there are limited studies on its potential dietary molecular toxicity and physiology. The present study was the first to use multi-omics-based approaches to explore the fish intestine-liver axis under dietary Zn exposure. Golden pompano Trachinotus ovatus were exposed to different dietary concentrations (78.4, 134.6, and 161.4 mg/kg as the control, low-dose Zn, and high-dose Zn groups, respectively) of Zn for 4-week. Low-dose Zn exposure significantly promoted the fish growth, whereas the high-dose Zn exposure reduced the fish growth. Co-analysis of 16S diversity, metagenome and transcriptome showed that the low-dose Zn enriched the intestinal microflora and changed the dominant microflora abundances (Proteobacteria, Fusobacteria, Firmicutes and Bacteroidetes), as well as activated the growth hormone metabolism in the liver. Meanwhile, the high-dose of Zn caused the intestinal microbiota dysbiosis, activated the Type VI secretion systems (T6SSs), and further triggered the oxidative stress response, immunity, and antiviral function of the liver. Multi-omics revealed the interference of long-term Zn dietary exposure on the intestine-liver axis. There was an apparent homeostasis of Zn accumulation in the fish tissues, but the window of dietary Zn nutritional requirements versus toxicity appeared to be narrow for the golden pompano. These results provided new insight into the adverse effects and regulatory mechanisms of dietary Zn requirements and toxicity in marine fish.

Role of metals in Alzheimer's disease.

Metal homeostasis in the central nervous system (CNS) is a crucial component of healthy brain function, because metals serve as enzymatic cofactors and are key components of intra- and inter-neuronal signaling. Metal dysregulation wreaks havoc on neural networks via induction and proliferation of pathological pathways that cause oxidative stress, synaptic impairment, and ultimately, cognitive deficits. Thus, exploration of metal biology in relation to neurodegenerative pathology is essential in pursuing novel therapies for Alzheimer's Disease and other neurodegenerative disorders. This review covers mechanisms of action of aluminum, iron, copper, and zinc ions with respect to the progressive, toxic accumulation of extracellular ß-amyloid plaques and intracellular hyperphosphorylated neurofibrillary tau tangles that characterizes Alzheimer's Disease, with the goal of evaluating the therapeutic potential of metal ion interference in neurodegenerative disease prevention and treatment. As neuroscientific interest in the role of metals in neurodegeneration escalates-in large part due to emerging evidence substantiating the interplay between metal imbalances and neuropathology-it becomes clear that the use of metal chelating agents may be a viable method for ameliorating Alzheimer's Disease pathology, as its etiology remains obscure. We conclude that, although metal therapies can potentially deter neurodegenerative processes, the most promising treatments will remain elusive until further understanding of neurodegenerative etiology is achieved. New research directions may best be guided by animal models of neurodegeneration, which reveal specific insights into biological mechanisms underlying dementia.

Dehydroeffusol Pprevents Amyloid ß1-42-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn2+ Toxicity.

Dehydroeffusol, a phenanthrene isolated from Juncus effusus, is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer's disease, here we examined the effect of dehydroeffusol on amyloid ß1-42 (Aß1-42)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aß1-42 was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aß1-42 injection, was rescued by dehydroeffusol administration. Aß staining (uptake) was not reduced in the dentate granule cell layer by pre-administration of dehydroeffusol for 6 days, while increase in intracellular Zn2+ induced with Aß1-42 was reduced, suggesting that pre-administration of dehydroeffusol prior to Aß1-42 injection is effective for Aß1-42-mediated neurodegeneration that was linked with intracellular Zn2+ toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aß1-42-mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn2+-binding proteins, in the dentate granule cell layer, which can capture Zn2+ from Zn-Aß1-42 complexes. The present study indicates that pre-administration of dehydroeffusol protects Aß1-42-mediated neurodegeneration in the hippocampus by reducing intracellular Zn2+ toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aß1-42-induced pathogenesis in Alzheimer's disease.

Zn2+ Intoxication of Mycobacterium marinum during Dictyostelium discoideum Infection Is Counteracted by Induction of the Pathogen Zn2+ Exporter CtpC.

Macrophages use diverse strategies to restrict intracellular pathogens, including either depriving the bacteria of (micro)nutrients such as transition metals or intoxicating them via metal accumulation. Little is known about the chemical warfare between Mycobacterium marinum, a close relative of Mycobacterium tuberculosis (Mtb), and its hosts. We use the professional phagocyte Dictyostelium discoideum to investigate the role of Zn2+ during M. marinum infection. We show that M. marinum senses toxic levels of Zn2+ and responds by upregulating one of its isoforms of the Zn2+ efflux transporter CtpC. Deletion of ctpC (MMAR_1271) leads to growth inhibition in broth supplemented with Zn2+ as well as reduced intracellular growth. Both phenotypes were fully rescued by constitutive ectopic expression of the Mtb CtpC orthologue demonstrating that MMAR_1271 is the functional CtpC Zn2+ efflux transporter in M. marinum Infection leads to the accumulation of Zn2+ inside the Mycobacterium-containing vacuole (MCV), achieved by the induction and recruitment of the D. discoideum Zn2+ efflux pumps ZntA and ZntB. In cells lacking ZntA, there is further attenuation of M. marinum growth, presumably due to a compensatory efflux of Zn2+ into the MCV, carried out by ZntB, the main Zn2+ transporter in endosomes and phagosomes. Counterintuitively, bacterial growth is also impaired in zntB KO cells, in which MCVs appear to accumulate less Zn2+ than in wild-type cells, suggesting restriction by other Zn2+-mediated mechanisms. Absence of CtpC further epistatically attenuates the intracellular proliferation of M. marinum in zntA and zntB KO cells, confirming that mycobacteria face noxious levels of Zn2+IMPORTANCE Microelements are essential for the function of the innate immune system. A deficiency in zinc or copper results in an increased susceptibility to bacterial infections. Zn2+ serves as an important catalytic and structural cofactor for a variety of enzymes including transcription factors and enzymes involved in cell signaling. But Zn2+ is toxic at high concentrations and represents a cell-autonomous immunity strategy that ensures killing of intracellular bacteria in a process called zinc poisoning. The cytosolic and lumenal Zn2+ concentrations result from the balance of import into the cytosol via ZIP influx transporters and efflux via ZnT transporters. Here, we show that Zn2+ poisoning is involved in restricting Mycobacterium marinum infections. Our study extends observations during Mycobacterium tuberculosis infection and explores for the first time how the interplay of ZnT transporters affects mycobacterial infection by impacting Zn2+ homeostasis.

Promotion of Zinc Tolerance, Acquisition and Translocation of Phosphorus in Mimosa pudica L. Mediated by Arbuscular Mycorrhizal Fungi.

Heavy metal contamination of soil is of increasing concern because of its potential risk to human health. In this study, two AMFs (Rhizophagus intraradices and Funneliformis mosseae) substantially increased the biomass of bashfulgrass in Zn-contaminated soil, even at Zn levels of up to 600 mg kg-1. Zn uptake in R. intraradices- and F. mosseae-mycorrhizal bashfulgrass was increased by 40-fold and 7-fold, respectively, when plants grown in Zn-contaminated (400 mg kg-1) soil. Elemental analysis showed that neither AMF had an effect on Zn concentration in plant tissues, including the roots and shoots. However, a significant increase of phosphorus (P) concentration was observed, suggesting the increased is from the improved use efficiency of soil nutrients by AMFs. Comparing the two AMFs, better growth performance with more biomass occurred with R. intraradices-inoculated bashfulgrass in Zn-contaminated soil. This is consistent with R. intraradices being more tolerant to Zn than F. mosseae, indicated by a higher colonization percentage in bashfulgrass roots. Taken together, our data indicate that AMFs possibly improve acquisition and translocation of P to promote increased biomass. Moreover, mycorrhiza did not enhance Zn accumulation in shoots and roots of bashfulgrass at the same Zn level. In the future, developing AMF (especially R. intraradices) inoculation of plants might be a desirable means of safe production of ornamental plants in metal-polluted soil.

Effect of phosphorus on the toxicity of zinc to the microalga Raphidocelis subcapitata.

The aim of this study was to evaluate the effect of phosphorus (P) on the toxicity of zinc (Zn) for the alga Raphidocelis subcapitata. P was provided in three concentrations: 2.3 x 10-4 mol L-1, 2.3 x 10-6 mol L-1 and 1.0 x 10-6 mol L-1. Algal cells were acclimated to the specific P concentrations before the start of the experiment. The chemical equilibrium software MINEQL+ 4.61 was employed to calculate the Zn2+ concentration. After acclimated, the algal cells were inoculated into media containing different Zn concentrations (0.09 x 10-6 mol L-1 to 9.08 x 10-6 mol L-1). The study showed that besides the reduction in algal growth rates, phosphorus had an important influence on the toxicity of zinc for microalga. The inhibitory Zn2+ concentration values for R. subcapitata were 2.74 x 10-6 mol L-1, 0.58 x 10-6 mol L-1 and 0.24 x 10-6 mol L-1 for the microalgae acclimated at P concentrations of 2.3 x 10-4 mol L-1, 2.3 x 10-6 mol L-1 and 1.0 x 10-6 mol L-1, respectively. Ecotoxicological studies should consider the interaction between metal concentrations and varying P values to provide realistic data of what occurs in phytoplankton communities in environments.

Foliar application of zinc and selenium alleviates cadmium and lead toxicity of water spinach - Bioavailability/cytotoxicity study with human cell lines.

The present study investigated the effects of foliar application of zinc (Zn) and selenium (Se) on bioavailability of Zn and Se and toxicity of cadmium (Cd) and lead (Pb) to different water spinach ecotypes (LA and HA) grown in slightly (XZ) or moderately (LJY) contaminated fields via in vitro digestion combined with Caco-2/HL-7702 cell model. The obtained results revealed that foliar application of Zn and Se promoted yield, increased total, bioaccessible and bioavailable fractions of Zn and Se in plants, indicating that foliar application is a feasible way of biofortification. Although there was no significant effect on liver cell proliferation (MTT), membrane stability (LDH) and hepatocyte enzyme (ALT and AST) activities, the obvious ecotype and soil dependent fluctuations of lipid peroxidation (MDA) and antioxidant enzyme (SOD, POD and CAT) activities in serum highly suggest that the low accumulator and clean field should be used in agricultural production rather than the high accumulator and contaminated farmland. Moreover, foliar application of Zn and Se improved nutritional quality of all water spinach genotypes in both fields, including increased Fe, vitamin C, cellulose and chlorophyll, maintained concentrations of potassium (K), manganese (Mn), copper (Cu), protein, and nitrate. These results demonstrate that this agricultural management practice may prove to be an effective approach for minimizing health risk and alleviating "hidden hunger" in the developing countries.

In vitro and In vivo toxicity analysis of zinc selenium/zinc sulfide (ZnSe/ZnS) quantum dots.

Despite the versatility of quantum dots (QDs) in optoelectronics and biomedical field, their toxicity risks remain a considerable hindrance for clinical applications. Cytotoxicity of Cadmium containing QDs is well documented and reveals that they are toxic to cells. Reports suggest that the presence of toxic elements at the QD core (e.g., cadmium, selenium) is responsible for its toxicity in in vivo and in vitro levels. Hence, here the toxicity of heavy metal free ZnSe/ZnS QDs on two scenarios were assessed, (i) HEK cells as in vitro system and (ii) Swiss Albino mice as in vivo model. Before toxicity analysis, QDs subjected to various optical and physico-chemical characterization methods such as absorption and emission spectra analysis, observation under U.V light, TEM, DLS, Zeta potential, FTIR, Raman and XPS spectra, ICP-OES, TGA and DTG curve. It is very necessary to characterize the synthesized QDs because their toxicity greatly influenced by the physico-chemical properties. On checking the vulnerability of HEK cells on exposure to ZnSe/ZnS QDs, the obtained results disclose that ZnSe/ZnS QDs showed merest impact on cellular viability at a concentration less than 100 µg/ml. Acute toxicity of 10 mg/kg ZnSe/ZnS QDs was studied in mice and no clinical or behavioural changes were observed. It did not induce any changes in haematological parameters and any loss of body or organ weight. Moderate pathological changes were evident only in the liver, all others organs like kidney, spleen and brain did not show any manifestations of toxicity. Current work lays substantial bedrock for safe biomedical and environmental application of ZnSe/ZnS QDs in near future.

Zinc application alleviates the adverse renal effects of arsenic stress in a protein quality control way in common carp.

The potential antagonistic mechanism between zinc (Zn) and arsenic (As) on renal toxicity was investigated in common carp. The results showed that by increased Zn efflux and retention (as reflected by zinc transporter 1 (ZnT-1), Zrt- and Irt- 1ike protein (ZIP) and metallothionein (MT) expression), Zn co-administration significantly recovered the antioxidant function (catalase, CAT) and the level of renal barrier function (Occludin, Claudins and Zonula Occludens) in comparison to As treatment. Interestingly, Zn co-administration with As resulted in carps undergoing reduction of heat shock response (HSPs), a low induction of autophagy flux (Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62)) and decreased endoplasmic reticulum (ER) stress (activating transcription factor 6 (ATF-6), inositol requiring-1α (IRE1) and PKR-like ER kinase (PERK)) in the aspect of mRNA or protein levels. All these alleviated protein quality control processes induced by Zn under As stress was correlated with the no longer loosen tight connection, less swollen endoplasmic reticulum as well as reduced formation of autophagosomes and autophagic vesicles. Mechanically, post-transcriptional regulated protein quantities compromising phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was demonstrated true causative forces inside the cell for Zn against As poisoning. In conclusion, we suggested the potential renal protective effect of Zn supplementation against As exposure by the modulation of protein quality control processes.