Zinc Exposure Research Articles

Associations of urinary zinc exposure with blood lipid profiles and dyslipidemia: Mediating effect of serum uric acid

The relationship between zinc (Zn) exposure and abnormal blood lipids including dyslipidemia is contentious. Serum uric acid (SUA) has been reported to be correlated to both Zn exposure and dyslipidemia. The underlying mechanisms of Zn exposure associated with blood lipids and the mediating effects of SUA remain unclear. Therefore, this study analyzed the data from Chinese 2110 adults (mean age: 59.0 years old) in rural areas across China to explore the associations of Zn exposure with blood lipid profiles and dyslipidemia, and to further estimate the mediating effects of SUA in these relationships. The study data showed that urinary Zn was associated with increased levels of blood lipid components triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). Moreover, an increased risk of dyslipidemia was observed in the study participants who had higher urinary Zn levels. Compared with the first quartile, the fourth quartile of urinary Zn concentration corresponded to the increase of TG (β = 0.20, 95 % CI: 0.12, 0.28), LDL-C (β = 0.06, 95 % CI: 0.01, 0.10) and dyslipidemia risk (OR = 2.16, 95 % CI: 1.50, 3.10), respectively. Elevated urinary Zn was also associated with higher levels of SUA and hyperuricemia risk. The SUA levels were positively related to total cholesterol (TC), TG, LDL-C levels and dyslipidemia risk. Mediation analyses revealed that SUA mediated 31.75 %, 46.16 % and 19.25 % of the associations of urinary Zn with TG, LDL-C levels and dyslipidemia risk, respectively. The subgroup and sensitivity analyses confirmed the positive associations between urinary Zn and blood lipid profiles and the mediating effect of SUA. The national population-based study further enhanced our understanding of the associations between Zn exposure and blood lipid profiles and mediating effect of SUA among generally healthy, middle-aged, and elderly individuals.

Zinc effects on bacteria: insights from Escherichia coli by multi-omics approach.

A long-term exposure of bacteria to zinc oxide and zinc oxide nanoparticles leads to major alterations in bacterial morphology and physiology. These included biochemical and physiological processes promoting the emergence of strains with multi-drug resistance and virulence traits. After the removal of zinc pressure, bacterial phenotype reversed back to the original state; however, certain changes at the genomic, transcriptomic, and proteomic level remained. Why is this important? The extensive and intensive use of supplements in animal feed effects the intestinal microbiota of livestock and this may negatively impact the health of animals and people. Therefore, it is crucial to understand and monitor the impact of feed supplements on intestinal microorganisms in order to adequately assess and prevent potential health risks.

Zinc Overload Induces Damage to H9c2 Cardiomyocyte Through Mitochondrial Dysfunction and ROS-Mediated Mitophagy.

Zinc homeostasis is essential for maintaining redox balance, cell proliferation, and apoptosis. However, excessive zinc exposure is toxic and leads to mitochondrial dysfunction. In this study, we established a zinc overload model by treating rat cardiomyocyte H9c2 cells with Zn2+ at different concentrations. Our results showed that zinc overload increased LDH and reactive oxygen species (ROS) levels, leading to cell death, mitochondrial membrane potential decrease and impaired mitochondrial function and dynamics. Furthermore, zinc overload activated the PINK1/Parkin signaling pathway and induced mitochondrial autophagy via ROS, while NAC inhibited mitophagy and weakened the activation of PINK1/Parkin pathway, thereby preserving mitochondrial biogenesis. In addition, our data also showed that Mfn2 deletion increased ROS production and exacerbated cytotoxicity induced by zinc overload. Our results therefore suggest that Zn2+-induced ROS generation causes mitochondrial autophagy and mitochondrial dysfunction, damaging H9c2 cardiomyocytes. Additionally, Mfn2 may play a key role in zinc ion-mediated endoplasmic reticulum and mitochondrial interactions. Our results provide a new perspective on zinc-induced toxicology.

Evolutionary consequences of microbiomes for hosts: impacts on host fitness, traits, and heritability.

An organism's phenotypes and fitness often depend on the interactive effects of its genome (Gh⁢o⁢s⁢t), microbiome (Gm⁢i⁢c⁢r⁢o⁢b⁢e), and environment (E). These G × G, G × E, and G × G × E effects fundamentally shape host-microbiome (co)evolution and may be widespread, but are rarely compared within a single experiment. We collected and cultured L⁢e⁢m⁢n⁢am⁢i⁢n⁢o⁢r (duckweed) and its associated microbiome from 10 sites across an urban-to-rural ecotone. We factorially manipulated host genotype and microbiome in two environments (low and high zinc, an urban aquatic stressor) in an experiment with 200 treatments: 10 host genotypes × 10 microbiomes × 2 environments. Host genotype explained the most variation in L.m⁢i⁢n⁢o⁢r fitness and traits, while microbiome effects often depended on host genotype (G × G). Microbiome composition predicted G × G effects: when compared in more similar microbiomes, duckweed genotypes had more similar effects on traits. Further, host fitness increased and microbes grew faster when applied microbiomes more closely matched the host's field microbiome, suggesting some local adaptation between hosts and microbiota. Finally, selection on and heritability of host traits shifted across microbiomes and zinc exposure. Thus, we found that microbiomes impact host fitness, trait expression, and heritability, with implications for host-microbiome evolution and microbiome breeding.

Associations of circulating multiple metals with the risk of incident hyperuricemia and the average annual change in uric acid levels

BackgroundHyperuricemia has been linked to exposure to certain metals in cross-sectional studies. However, prospective studies evaluating the associations of multiple metal exposures with incident hyperuricemia are scarce. ObjectivesTo prospectively investigate the associations of multiple metal/metalloid concentrations with incident hyperuricemia as well as average annual change in uric acid levels in a longitudinal cohort. MethodsA longitudinal cohort study included 3957 subjects who were free of cardiovascular disease with certain risk factors for cardiovascular disease at baseline. Incident hyperuricemia was ascertained if serum uric acid level was ≥ 420 μmol/L for men and ≥ 360 μmol/L for women during the follow-up visit in 2013. The relationships between 17 single plasma metals/metalloids and incident hyperuricemia were assessed using unconditional logistic regression models. For metals/metalloids significantly related to incident hyperuricemia, we further utilized generalized linear regression models to evaluate their associations with the average annual change in uric acid levels. Finally, we applied the weighted quantile sum (WQS) regression to investigate the joint effects of metals/metalloids on hyperuricemia risk and uric acid changes, and to identify the most significant metals. ResultsAfter adjusting for potential confounders, plasma aluminum, arsenic, barium, lead, strontium, vanadium, and zinc concentrations were positively associated with incident hyperuricemia in both main analyses and sensitivity analyzes. Compared to the lowest quartiles, participants in the highest quartiles had 63 %−125 % higher risks of incident hyperuricemia (all FDR < 0.05). Furthermore, the positive associations of these seven metals with an average annual uric acid increase reinforced the findings. Finally, the WQS analyses showed that plasma metals mixtures were positively associated with the risk of incident hyperuricemia (OR: 1.47; 95 % CI: 1.23, 1.76) and the average annual change in uric acid levels (β: 3.17; 95 % CI: 2.42, 3.93), and strontium and vanadium were the most heavily weighted metals, respectively. ConclusionOur findings identify aluminum, arsenic, barium, lead, strontium, vanadium, and zinc exposures as independent risk factors for hyperuricemia and provide new insights into the prevention of hyperuricemia.

Employing molecular, chemical and physiological techniques using Crassostrea virginica to assess ecosystem health along coastal South Carolina and North Carolina, United States

Natural and anthropogenic environmental impacts can introduce contaminants into sensitive habitats, threatening ecosystems and human health. Consistent monitoring of coastal areas provides critical environmental assessment data. Sediments and Eastern Oyster (Crassostrea virginica) tissues were collected at fourteen South Carolina (SC) and four North Carolina (NC) sites as part of the National Oceanic and Atmospheric Administration's Mussel Watch environmental monitoring program. Cellular and molecular techniques were employed to measure C. virginica stress response, specifically, Lipid Peroxidation (LPx), Glutathione (GSH), and qPCR techniques. Gene specific primers targeted for detecting oxidative stress and cellular death were developed in C. virginica to gauge response to current environmental conditions using gill and hepatopancreas (HP) tissue. In order to validate gene specific markers as additional assessment tools, a 96 h zinc (Zn) laboratory exposure was performed. Cellular biomarker data revealed tissue specific responses. Hepatopancreas data showed C. virginica exhibited stress through the lipid peroxidation assay amongst sampling sites, however, response was managed through glutathione detoxification. Gill tissue data had significantly lower levels of cellular biomarker response compared to hepatopancreas. Molecular biomarkers targeting these cellular stress pathways through qPCR analysis show upregulation of Metallothionein in hepatopancreas and gill tissue with a concurrent > 2-fold upregulation in the detoxification marker Superoxide Dismutase (SOD) at three NC sites. SC sites displayed higher stress levels through LPx assays and down-regulation in GPx gene activity. Laboratory zinc exposure revealed no significance in cellular biomarker results, however, molecular data showed gills responding to zinc treatment through upregulation of Metallothionein, SOD and Cathepsin L, indicating an acute response in gills. Collectively, chemical, cellular and molecular methods clarify sentinel stress response of biological impacts and aid in evaluating environmental health in coastal ecosystems. This combined methodological approach provides a detailed analysis of environmental conditions and improves land-use management decisions.

Hair Heavy Metals and Food Consumption in Residents of Chengdu: Factors, Food Contribution, and Health Risk Assessment.

Heavy metal pollution is one of the most pressing issues threatening food security and human health. This study assesses heavy metal (chromium, cadmium, copper, zinc, nickel, and lead) exposure via hair metal concentrations in Chengdu residents, reflecting metal intake from food consumption. From June 2020 to February 2021, a sampling survey was conducted on residents' hair (n=182) and food (n=301) in six main urban areas of Chengdu. The concentrations of heavy metals in hair and food were analyzed by inductively coupled plasma mass spectrometry, and the results showed that the residents of Chengdu City had high hair concentrations of Cd (0.17±0.03 mg kg-1) and Zn (293±21.3 mg kg-1). Gender significantly affected the hair Cr, Zn, and Ni concentrations. Based on the survey results obtained from Chengdu City residents, the habits and diet structure are assessed for the influence of six heavy metals in the hair of the residents. Adolescents' (13-18 years old) hair had significantly higher Pb concentrations than adults (19-59 years old). The concentration of Ni in hair was affected by perming and dyeing habits. For dietary exposure, cereals and meat were the main contributors to the residents' daily intake of heavy metals. The bioaccessibility of Cr, Cd, Cu, Zn, Ni, and Pb in food was 2.45-74.67%, 10.6-78.7%, 13.4-82.5%, 8.89-89.2%, 7.70-85.1%, and 15.4-86.2%, respectively. In health risk evaluation based on the bioaccessible fraction of six heavy metals, the hazard quotient of each heavy metal in food was less than 1, indicating no potential non-carcinogenic risk.

Evaluating the Protectiveness of a Bioavailability-Based Environmental Quality Standard for the Protection of Aquatic Communities from Zinc Toxicity Based on Field Evidence.

Environmental quality standards (EQS) are typically derived from the results of laboratory studies on single species. There is always uncertainty surrounding the protectiveness of an EQS when applied to real ecosystems containing a multitude of chemical and physical stressors. Quantile regression was used with field biological data on invertebrates in United Kingdom waters to identify taxa that are responsive to bioavailable zinc exposures. A threshold based on the total abundance of eight responsive taxa is used as an indicator of the overall ecosystem sensitivity. The inclusion of some responsive but insensitive taxa in this ecological metric could bias the results toward a higher threshold. The least responsive species were progressively removed from the collective ecological metric, basing the analysis on a progressively smaller number of the more responsive species. Quantile regression analysis at the 95th quantile for the three most responsive taxa resulted in a 10% effect concentration of 14.8 µg L-1 bioavailable zinc, suggesting that the EQS of 10.9 µg L-1 bioavailable zinc is sufficiently protective of sensitive members of the invertebrate community. There is a compromise between the robustness of the analysis and the sensitivity of the subcommunity that it is based on. Analyses based on fewer taxa provide a more sensitive result. This approach assessed real ecosystem data and evaluated the uncertainty associated with the protectiveness of the EQS for zinc. The zinc EQS is sufficiently protective of sensitive members of benthic macroinvertebrate communities under real environmental conditions, including a mix of multiple substances. Environ Toxicol Chem 2023;42:1010-1021. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Comparative transcriptome and antioxidant biomarker response reveal molecular mechanisms to cope with zinc ion exposure in the unicellular eukaryote Paramecium

The development of industry has resulted in excessive environmental zinc exposure which has caused various health problems in a wide range of organisms including humans. The mechanisms by which aquatic microorganisms respond to environmental zinc stress are still poorly understood. Paramecium, a well-known ciliated protozoan and a popular cell model in heavy metal stress response studies, was chosen as the test unicellular eukaryotic organism in the present research. In this work, Paramecium cf. multimicronucleatum cells were exposed in different levels of zinc ion (0.1 and 1.0 mg/L) for different periods of exposure (1 and 4 days), and then analyzed population growth, transcriptomic profiles and physiological changes in antioxidant enzymes to explore the toxicity and detoxification mechanisms during the zinc stress response. Results demonstrated that long-term zinc exposure could have restrained population growth in ciliates, however, the response mechanism to zinc exposure in ciliates is likely to show a dosage-dependent and time-dependent manner. The differentially expressed genes (DEGs) were identified the characters by high-throughput sequencing, which remarkably enriched in the phagosome, indicating that the phagosome pathway might mediate the uptake of zinc, while the pathways of ABC transporters and Na+/K+-transporting ATPase contributed to the efflux transport of excessive zinc ions and the maintenance of osmotic balance, respectively. The accumulation of zinc ions triggered a series of adverse effects, including damage to DNA and proteins, disturbance of mitochondrial function, and oxidative stress. In addition, we found that gene expression changed significantly for metal ion binding, energy metabolism, and oxidation-reduction processes. RT-qPCR of ten genes involved in important biological functions further validated the results of the transcriptome analysis. We also continuously monitored changes in activity of four antioxidant enzymes (SOD, CAT, POD and GSH-PX), all of which peaked on day 4 in cells subjected to zinc stress. Collectively, our results indicate that excessive environmental zinc exposure initially causes damage to cellular structure and function and then initiates detoxification mechanisms to maintain homeostasis in P. cf. multimicronucleatum cells.

Temporal relationship of the orphan receptor TR3 translocation and expression with zinc-induced apoptosis in prostate cancer cells.

This study aimed to investigate the precise mechanism of zinc-induced apoptosis in human prostate cell lines PC-3 and LNCaP and explore its relationships with the translocation and expression of the orphan receptor TR3 and cytochrome c. The effects of zinc exposure on apoptosis levels were examined in both PC-3 and LNCaP cells. These cells were treated with exogenous ZnCl2 (100 µM) for 0, 4, 8, 12, and 24 h. Dansylaminoethyl-cyclen (DAEC) fluorescent probe was applied to visualize cellular zinc localization. Zinc-induced apoptosis was identified by Hoechst nuclear staining and flow cytometry analysis. TR3 messenger RNA (mRNA) expression levels were detected by real time-quantitative polymerase chain reaction (PCR). TR3 protein localization and mitochondrial release of cytochrome c were identified by immunofluorescence microscopy. Mitochondrial membrane potential collapse under fluorescence microscopy was examined with a MitoLight probe. Zinc exposure led to gradually increasing apoptosis levels in both LNCaP and PC-3 cells over the 24-h treatment period. The apoptotic effects could be observed as early as after 4 h of zinc treatment in PC-3 cells, with this being seen at 8 h in LNCaP cells. The apoptosis levels of both PC-3 and LNCaP cells began to increase significantly from 8 to 24 h when necrotic cells were also found. TR3 protein translocation from the nucleus to the mitochondria was noted and was accompanied by cytochrome c release into the cytosol from the mitochondria. Interestingly, no significant changes in TR3 mRNA expression levels were observed after zinc treatment. However, the mitochondrial membrane potential of both PC-3 and LNCaP cells gradually disappeared following extended zinc exposure. Zinc-induced apoptosis could be regulated through TR3 protein translocation from the nucleus to the mitochondria in prostate cancer cells without notable changes in TR3 mRNA levels. The direct effect of zinc on the mitochondria was associated with the release of cytochrome c into the cytosol through the mitochondrial targeting of TR3 protein.

Use of zinc deposited in deciduous teeth as a retrospective measurement of dietary zinc exposure during early development.

We proposed that zinc (Zn) deposition in deciduous teeth would be a timed record of exposure to this essential micronutrient over very early life. We tested this hypothesis by gathering information on the maternal and child's diet during pregnancy and early infancy and measuring mineral deposition in the dentine at points during deciduous tooth development. We developed a short food frequency questionnaire (S-FFQ) to record consumption of food containing Zn during pregnancy and over the first year of life of the child in an Indonesian population. Zn, Sr and Ca were measured by laser ablation ICP-MS in a series of points across the developmental timeline in deciduous teeth extracted from 18 children undergoing the process as part of dental treatment whose mothers completed the SFFQ. Mothers and children were classified into either high Zn or low Zn groups according to calculated daily Zn intake. The Zn/Sr ratio in dentine deposited over late pregnancy and 0-3 months post-partum was higher (p < 0.001, 2-way ANOVA; p < 0.05 by Holm-Sidak post hoc test) in the teeth of children of mothers classified as high Zn consumers (n = 10) than in children of mothers classified as low Zn consumers (n = 8). The S-FFQ was validated internally as adequately accurate to measure zinc intake retrospectively during pregnancy and post-partum (∼7 years prior) by virtue of the correlation with measurements of zinc in deciduous teeth. The ratio of Zn/Sr in deciduous teeth appears to be a biomarker of exposure to zinc nutrition during early development and offers promise for use as a record of prior exposure along a timeline for research studies and, potentially, to identify individuals at heightened risk of detrimental impacts of poor early life zinc nutrition on health in later life and to implement preventative interventions.

Effects of Lead and Zinc Exposure on Uptake and Exudation Levels, Chlorophyll-a, and Phycobiliproteins in Sarcodia suiae

The present study aimed to determine the changes in the biosorption, bioaccumulation, chlorophyll-a (chl-a), phycobiliproteins, and exudation in the red seaweed Sarcodia suiae exposed to lead and zinc. The seaweed was exposed to ambient lead and zinc environments for 5 days before being transferred to fresh seawater, and the changes in biodesorption, biodecumulation, chl-a, and phycobiliprotein levels in S. suiae were investigated. Lead and zinc biosorption and bioaccumulation in the seaweed increased with the increase in the lead and zinc concentrations and exposure times. Meanwhile, the biosorption and bioaccumulation of zinc in the seaweed following exposure to zinc were significantly higher (p < 0.05) than the biosorption and bioaccumulation of lead in the seaweed following exposure to lead with the same concentration at each exposure time. The chl-a, phycoerythrin (PE), phycocyanin (PC), and allophycocyanin (APC) contents in the seaweed significantly decreased with the increase in the lead and zinc concentrations and exposure times. The chl-a, PE, PC, and APC contents in S. suiae, which was exposed to 5 Pb2+ mg/L for 5 days, were significantly higher (p < 0.05) than those in the seaweed exposed to zinc at the same concentration and for the same exposure times. In the lead and zinc exudation tests, the highest biodesorption and biodecumulation were observed on the 1st day of exudation after the seaweed was transferred to fresh seawater. The residual percentages of the lead and zinc in the seaweed cells were 15.86% and 73.08% after 5 days of exudation, respectively. The biodesorption rate and biodecumulation rate of the seaweed exposed to lead were higher than those of the seaweed exposed to zinc. However, the effect of lead on chl-a and phycobiliproteins was greater than that of zinc. This might be the result of lead not being a necessary metal for these algae, whereas zinc is.

Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus: Exploring potential role of miR-144-3p in zinc-induced insulin resistance

Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.

Oxidative stress, neurotoxicity, and intestinal microbial regulation after a chronic zinc exposure: an experimental study on adult zebrafish (Danio rerio)

Abstract Zinc is one of the heavy metals present in textile wastewater with high concentrations. However, the chronic toxic effects of zinc on aquatic vertebrates are still ambiguous. Zinc accumulation in zebrafish after chronic zinc exposure and toxic effects on the intestines, muscles, and gills were investigated in this study. The results showed that a significant accumulation of zinc in the intestine, muscle, and gill was observed after 25 d of zinc exposure. The toxic effects of zinc were mainly in the form of zinc-induced oxidative stress in zebrafish, potential neurotoxicity, and changes in intestinal microbes. Significant changes in the levels of superoxide dismutase, catalase, metallothionein, glutathione, and malondialdehyde indicated that zinc damaged the antioxidant system of adult zebrafish. Zinc exposure resulted in a significant decrease in acetylcholinesterase activity and abnormal neural signaling. Furthermore, zinc exposure resulted in increased intestinal microbial richness and decreased the Simpson index in adult zebrafish. At the phylum and genus levels, the predominant microbes in the intestine are altered by zinc. In summary, this study provides an analysis of the toxic effects of chronic zinc exposure on adult zebrafish and the potential mechanisms, which are important for assessing the dual effects of zinc on aquatic organisms.

Lipidomic and Metallomic Alteration of Caenorhabditis elegans after Acute and Chronic Manganese, Iron, and Zinc Exposure with a Link to Neurodegenerative Disorders.

Parkinson's disease (PD) progresses with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain. The superior mechanisms and the cause of this specific localized neurodegeneration is currently unknown. However, experimental evidence indicates a link between PD progression and reactive oxygen species with imbalanced metal homeostasis. Wild-type Caenorhabditis elegans exposed to redox-active metals was used as the model organism to study cellular response to imbalanced metal homeostasis linked to neurodegenerative diseases. Using modern hyphenated techniques such as capillary electrophoresis coupled to inductively coupled plasma mass spectrometry and ultrahigh-performance liquid chromatography mass spectrometry, alterations in the lipidome and metallome were determined in vivo. In contrast to iron, most of the absorbed zinc and manganese were loosely bound. We observed changes in the phospholipid composition for acute iron and manganese exposures, as well as chronic zinc exposure. Furthermore, we focused on the mitochondrial membrane alteration due to its importance in neuronal function. However, significant changes in the inner mitochondrial membrane by determination of cardiolipin species could only be observed for acute iron exposure. These results indicate different intracellular sites of local ROS generation, depending on the redox active metal. Our study combines metallomic and lipidomic alterations as the cause and consequence to enlighten intracellular mechanisms in vivo, associated with PD progression. The mass spectrometry raw data have been deposited to the MassIVE database (https://massive.ucsd.edu) with the identifier MSV000090796 and 10.25345/C51J97C8F.

Crosstalk Between the Mitochondrial Dynamics and Oxidative Stress in Zinc-induced Cytotoxicity.

Zinc is an essential trace element, which plays an important role in multiple biological activities. However, excessive exposure to zinc can cause toxic damage to living organism. Here, we investigated the relationship between oxidative stress and mitochondrial dynamics in the zinc-induced cytotoxicity. Results showed that excess exposure to zinc could significantly reduce cell viability and induce cell vacuolation in PK-15 cells. Additionally, zinc exposure caused mitochondrial dynamics disorder, manifested as mitochondrial fission, and the elevated mRNA level of Drp1 and downregulated mRNA levels of OPA1, Mfn1, and Mfn2. Meanwhile, zinc could induce oxidative damage, evidenced by the increasing levels of hydrogen peroxide, malondialdehyde, lipid peroxidation, oxidized form of nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate, oxidized glutathione/glutathione, superoxide dismutase activity, and the mRNA expression of SOD-1 and NOQ1, and decreasing levels of catalase activity, glutathione peroxidase activity, glutathione reductase activity, and the mRNA expression of CAT, and GPX1. Interestingly, N-acetyl-L-cysteine, an inhibitor for oxidative stress, could reduce the mitochondrial fission under zinc treatment. Besides, Mdivi-1, a mitochondrial fission inhibitor, could relieve oxidative stress caused by excess zinc. Ingeneral, these results suggested that mitochondrial fission and oxidative stress induced by zinc were interrelated in PK-15 cells, which is conducive to explore the new mechanism of zinc toxicity and proposes a theoretical foundation for selecting effective drugs to alleviate the toxic effects caused by zinc.

Examining the impact of zinc on horizontal gene transfer in Enterobacterales

Antimicrobial resistance is one of the main international health concerns for humans, animals, and the environment, and substantial efforts have focused on reducing its development and spread. While there is evidence for correlations between antimicrobial usage and antimicrobial resistance development, specific information on the effect of heavy metal/antimicrobial usage on bacterial conjugation is more limited. The aim of this study was to investigate the effects of zinc and antimicrobials in different concentrations on horizontal gene transfer of an ampicillin resistance gene, using a multi-drug resistant Escherichia coli donor strain and three different Salmonella enterica serovars as recipient strains. Differences in conjugation frequencies for the different Salmonella recipients were observed, independent of the presence of zinc or the antimicrobials. Selective pressure on the recipient strains, in the form of ampicillin, resulted in a decrease in conjugation frequencies, while, the presence of rifampicin resulted in increases. Zinc exposure affected conjugation frequencies of only one of the three recipient strains, thus the effect of zinc on conjugation frequencies seemed to be concentration and strain dependent. Furthermore, differences in growth rates due to plasmid carriage were observed for one of the Salmonella strains.

Changes in aggression and locomotor behaviors in response to zinc is accompanied by brain cell heterogeneity and metabolic and circadian dysregulation of the brain-liver axis

Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46–1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl2-low) and 1.5 (ZnCl2-high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl2-low, 0.48 (∼0.51); ZnCl2-high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid β-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish.

Microbial community shifts induced by plastic and zinc as substitutes of tire abrasion

Aquatic environments serve as a sink for anthropogenic discharges. A significant part of the discharge is tire wear, which is increasingly being released into the environment, causing environmental disasters due to their longevity and the large number of pollutants they contain. Main components of tires are plastic and zinc, which therefore can be used as substitutes for tire abrasion to study the effect on microbial life. We investigate environmentally realistic concentrations of plastic and zinc on a freshwater microeukaryotic community using high-throughput sequencing of the 18S V9 region over a 14-day exposure period. Apart from a generally unchanged diversity upon exposure to zinc and nanoplastics, a change in community structure due to zinc is evident, but not due to nanoplastics. Evidently, nanoplastic particles hardly affect the community, but zinc exposure results in drastic functional abundance shifts concerning the trophic mode. Phototrophic microorganisms were almost completely diminished initially, but photosynthesis recovered. However, the dominant taxa performing photosynthesis changed from bacillariophytes to chlorophytes. While phototrophic organisms are decreasing in the presence of zinc, the mixotrophic fraction initially benefitted and the heterotrophic fraction were benefitting throughout the exposure period. In contrast to lasting changes in taxon composition, the functional community composition is initially strongly imbalanced after application of zinc but returns to the original state.

Cross-sectional and longitudinal associations of urinary zinc with glucose-insulin homeostasis traits and type 2 diabetes: Exploring the potential roles of systemic inflammation and oxidative damage in Chinese urban adults

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2′-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2′-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.