Ni Exposure Research Articles

Genome-wide analysis of miR172-mediated response to heavy metal stress in chickpea (Cicer arietinum L.): physiological, biochemical, and molecular insights

BackgroundChickpea (Cicer arietinum L.), a critical diploid legume in the Fabaceae family, is a rich source of protein, vitamins, and minerals. However, heavy metal toxicity severely affects its growth, yield, and quality. MicroRNAs (miRNAs) play a crucial role in regulating plant responses to both abiotic and biotic stress, including heavy metal exposure, by suppressing the expression of target genes. Plants respond to heavy metal stress through miRNA-mediated regulatory mechanisms at multiple physiological, biochemical, and molecular levels. Although the Fabaceae family is well represented in miRNA studies, chickpeas have been notably underrepresented. This study aimed to investigate the effects of heavy metal-induced stress, particularly from 100 µM concentrations of cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), and 30 µM arsenic (As), on two chickpea varieties: ILC 482 (sensitive) and Azkan (tolerant). The assessment focused on physiological, biochemical, and molecular parameters. Furthermore, a systematic characterization of the miR172 gene family in the chickpea genome was conducted to better understand the plant’s molecular response to heavy metal stress.ResultsVariance analysis indicated significant effects of genotype (G), treatment (T), and genotype-by-treatment (GxT) interactions on plant growth, physiological, and biochemical parameters. Heavy metal stress negatively impacted plant growth in chickpea genotypes ILC 482 and Azkan. A reduction in chlorophyll content and relative leaf water content was observed, along with increased cell membrane damage. In ILC 482, the highest hydrogen peroxide (H₂O₂) levels in shoot tissue were recorded under As, Cd, and Ni treatments, while in Azkan, peak levels were observed with Pb treatment. Malondialdehyde (MDA) levels in root tissue were highest in ILC 482 under Cd and Ni exposure and in Azkan under As, Cr, and Cd treatments. Antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX), were significantly elevated under heavy metal stress in both genotypes. Gene expression analysis revealed upregulation of essential antioxidant enzyme genes, such as SOD, CAT, and APX, with APX showing notable increases in both shoot and root tissues compared to the control. Additionally, seven miR172 genes (miR172a, miR172b, miR172c, miR172d, miR172e, miR172f, and miR172g) were identified in the chickpea genome, distributed across five chromosomes. All genes exhibited conserved hairpin structures essential for miRNA functionality. Phylogenetic analysis grouped these miR172 genes into three clades, suggesting strong evolutionary conservation with other plant species. The expression analysis of miR172 and its target genes under heavy metal stress showed varied expression patterns, indicating their role in enhancing heavy metal tolerance in chickpea.ConclusionsHeavy metal stress significantly impaired plant growth and physiological and biochemical parameters in chickpea genotypes, except for cell membrane damage. The findings underscore the critical role of miR172 and its target genes in modulating chickpea’s response to heavy metal stress. These insights provide a foundational understanding for developing stress-tolerant chickpea varieties through miRNA-based genetic engineering approaches.

Occupational exposure to nickel or hexavalent chromium and the risk of lung cancer (SYNERGY)

Abstract Background Hexavalent chromium (Cr(VI)) and nickel (Ni) are known occupational carcinogens, with frequent exposures, for example, in welding-related activities. However, limited evidence exists on the exposure-response relationship of Cr(VI) or Ni with lung-cancer risk. We estimated lung-cancer risks based on quantitative indices of occupational exposure to each metal, and their interaction with smoking habits. Methods Fourteen case-control studies from Europe and Canada (16,901 cases, 20,965 control subjects) were pooled. A measurement-based job-exposure matrix was used to estimate year- and region-specific exposure levels for Cr(VI) and Ni, which were linked to the study subjects’ occupational histories. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for study, age group, smoking, and exposure to other occupational lung carcinogens. Results The OR for the highest quartile (>99.5 μg/m3-years) of cumulative exposure to Cr(VI) in men was 1.32 (95% CI 1.19-1.47) and for nickel (highest quartile >78.1 μg/m3-years) OR = 1.29 (95% CI 1.15-1.45). Corresponding effect estimates in women were slightly lower. The joint effects of Cr(VI) and nickel with smoking were generally greater than additive. Conclusions We observed positive exposure-response relationships in the low-dose range of Cr(VI) and Ni exposures, based on a large study population including detailed information on smoking habits and a measurement-based job-exposure matrix. Although, we cannot rule out a combined classical measurement and Berkson error structure that may have caused bias in our risk estimates, our results provide empirical evidence to further specify preventive measures at the workplace in order to protect workers from hazardous substances. Key messages • Relatively low cumulative levels of occupational exposure to Cr(VI) and Ni were associated with increased ORs for lung cancer, particularly in men. • Important empirical insights for the prevention of cancer at the workplace can be drawn from the results.

Impact of lead and nickel contamination on metabolic health: Associations with diabetes mellitus in a pakistani cohort

Environmental exposure to heavy metals, particularly lead (Pb) and nickel (Ni), is implicated in chronic metabolic diseases, including diabetes mellitus (DM). This cross-sectional study assessed the Pb and Ni levels in groundwater using ICP-OES and urine samples collected from 2688 participants using ICP-MS. We aimed to establish the associations between Pb and Ni exposure and risk factors for DM and metabolic disorders. Groundwater analysis revealed the elevated levels of total dissolved solids, electrical conductivity, hardness, turbidity, Ni, and Pb, exceeding the WHO guidelines. The mean concentration of Pb in groundwater samples of study area was 0.025 mg/L which was higher than the WHO permissible limit of 0.01 mg/L. Similarly the mean concentration of Ni in groundwater samples of study area was 0.038 mg/L which was also higher than the WHO permissible limit of 0.02 mg/L. In human study, participants, categorized into Pb-detected and Ni-detected groups, exhibited significantly higher Pb and Ni levels and non-exposed non-diabetic groups. Ni-detected diabetics showed elevated Ni levels compared to non-exposed non-diabetics. Similarly, Pb-detected diabetics showed elevated Pb levels compared to non-exposed non-diabetics. These findings suggest a potential contribution of Pb and Ni exposure to DM development. The study also identified associations between heavy metal exposure and disruptions in various biomarkers related to DM, lipid profile, inflammation, oxidative stress, liver function, and kidney function. Pb-detected diabetics demonstrated elevated levels of glycemic index biomarkers, including fasting blood glucose (P < 0.0001) and HbA1c (P < 0.0001). Ni-detected diabetics exhibited increased inflammatory markers, such as CRP (P < 0.0001) and IL-6 (P < 0.0001). Both Pb and Ni exposure were associated with dyslipidemia, as indicated by elevated levels of total cholesterol (P < 0.0001) and LDL (P < 0.0001). Additionally, heavy metal exposure was linked to impaired liver and kidney function, supported by elevated levels of AST (P < 0.0001), ALT (P < 0.0001), creatinine (P < 0.0001), and blood urea nitrogen (P < 0.0001), with Pb exposure also associated with higher levels of MDA (P < 0.0001). Correlation analyses demonstrated significant associations between urinary Pb and Ni concentrations and various biomarkers related to DM and metabolic disorders. In conclusion, this study provides substantial evidence linking Pb and Ni exposure to the development of DM and metabolic disorders in a Pakistani population, emphasizing the need for strict regulations and preventive measures to reduce heavy metal contamination and safeguard public health. Future longitudinal studies and interventions are warranted to elucidate mechanistic links between heavy metal exposure and metabolic diseases.

The mediating role of abnormal ZEB1 methylation in the association between nickel exposure and non-syndromic orofacial cleft

Our previous study found a positive relationship between fetal nickel exposure and the risk of OFCs. The teratogenic mechanism of nickel is not clear. In this study, we aim to examine the mediating effect of DNA methylation on the association of nickel(Ni) exposure with NSOFC in fetuses. 10 cases and 10 controls was used for screening target gene by Illumina Infinium Methylation EPIC(850k) BeadChip. 36 cases and 78 controls was conducted to determine DNA methylation level of selected gene in umbilical cord blood by Mass spectrometry assay. Mediation analysis was used to evaluate the potential mediating effect of selected gene methylation on the relation between concentrations of Ni and the risk for NSOFC. In the discovery stage, ZEB1 gene was identified to be hypermethylated in both nickel exposure and NSOFC group for validation. In the verification stage, the overall average methylation level of ZEB1 was significant higher in NSOFC cases(median = 8.70, interquartile range(IQR): 5.75–11.53) as compared to controls (median = 5.35, IQR: 4.30–7.78). The risk for NSOFC was increased by 1.43-fold with hypermethylation of ZEB1. Significant correlation was observed between concentrations of Ni in umbilical cord and methylation level of ZEB1. The hypermethylation of ZEB1 had a mediating effect by 20.47 % of total effect of Ni on NSOFC risk. Hypermethylation of ZEB1 is associated with the risk for NSOFC and may partially explain the association between Ni exposure and NSOFC risk. Our findings provide new insights into the epigenetic mechanisms underlying NSOFC and suggesting potential targets for future therapeutic interventions.

Enhanced health risk of soil heavy metal exposure following an extreme rainstorm under climate change

Widespread concerns raised in changes in the health risk of soil heavy metals exposure due to extreme rainstorm under climate change. However, the impacts of extreme rainstorm on human exposure risk and the underlying mechanisms are still unclear. In this study, soil properties, speciation distribution and bioaccessibility of Ni, Cu, Zn, Cd and Pb in soil samples, which were collected before and after extreme rainstorm, were measured, subsequently the soil oral exposure risk of heavy metals was assessed based on bioaccessibility. Results indicate that extreme rainstorm can significantly enhance the accumulated non-carcinogenic and carcinogenic exposure risk by 10.1–188.3 %, with lowland soil posing 1.3–1.7 times higher risk than highland soil. The increase in exposure risk varies among elements in highland and lowland soil. Specifically, the exposure risk for Cd and Pb increased by 2.5–9.7 times, whereas that for Cu decreased by 43.2 % - 60.6 %. The risk of Zn and Ni exposure exhibits complex trends, with an increase of 37.2 %–104.8 % in lowland soil but a decrease of 9.4 %–46.5 % in highland soil. Bioaccessibility variations are the primary risk factors for soil heavy metal exposure during extreme rainstorms, not total concentration. Mechanistically, the extreme rainstorm directly increases soil moisture content and reduce organic matter concentration, leading to an increment in the proportion of bio-utilization speciation and decrement in the speciation bounding to Fe/Mn oxides of soil heavy metals. Furthermore, the bioaccessibility of soil heavy metal positively correlates with their bio-utilization speciation and negatively correlates with their speciation bounding to Fe/Mn oxides, which ultimately increasing exposure risk. Our study suggests the necessity that attentions should be paid to the enhanced health risk associated with soil heavy metal exposure following extreme rainstorm, particularly for population residing in lowland areas.

Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells

Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2). The results reveal a synergistic effect of Co and Ni, leading to significantly higher number of differentially expressed genes (DEGs) compared to individual exposure. There was a clear enrichment of Nrf2 regulated genes linked to pathways such as glycolysis, iron and glutathione metabolism, and sphingolipid metabolism, confirmed by targeted analysis. Co and Ni exposure alone and combined caused nuclear Nrf2 translocation, while only combined exposure significantly affects iron and glutathione metabolism, evidenced by upregulation of HMOX-1 and iron storage protein FTL. Both metals impact sphingolipid metabolism, increasing dihydroceramide levels and decreasing ceramides, sphingosine and lactosylceramides, along with diacylglycerol accumulation. By combining transcriptomics and analytical methods, this study provides valuable insights into molecular mechanisms of Co and Ni toxicity, paving the way for further understanding of metal stress.

Exploring the neuroprotective role of melatonin against nickel-induced neurotoxicity in the left hippocampus.

Previous studies have demonstrated that the hippocampus, a crucial region for memory and cognitive functions, is particularly vulnerable to adverse effects of exposure to heavy metals. Nickel (Ni) is a neurotoxic agent that, primarily induces oxidative stress, a process known to contribute to cellular damage, which consequently affects neurological functions. The antioxidant properties of melatonin are a promising option for preventing the adverse effects of Ni, especially by protecting cells against oxidative stress and related damage. In our investigation of the potential neuroprotective effects of melatonin against Ni-induced neurotoxicity, we chose to administer melatonin through intraperitoneal injection in rats following an intrahippocampal injection of Ni into the left hippocampus. This approach allows us a targeted investigation into the influence of melatonin on the neurotoxic effects of Ni, particularly within the crucial context of the hippocampus. In the present study, we demonstrated that melatonin efficiency reduced lactate dehydrogenase level, and preserved antioxidant enzyme activities in Ni-exposed hippocampal tissue. It also mitigated the decline in superoxide dismutase and catalase activities. On the other hand, melatonin could act directly by reducing reactive oxygen species Ni-induced overproduction. Taking to gather these two potential mechanisms of action could be responsible for the adverse effect of Ni on the behavioral alteration observed in our study. This study provides significant insights into the potential of melatonin to mitigate the detrimental effects of Ni on the brain, particularly into the hippocampal region, suggesting its possible implications for the treatment of neurological disorders related to Ni exposure.

A comprehensive perspective on potentially hazardous elements (PHEs) bound with particulate matters in ambient air of landfill sites: a systematic review and probabilistic risk assessment.

Air pollution from Potentially Hazardous Elements bound with particulate matter (PHEs bound PM) in landfill air is a significant concern for human health. To date, no comprehensive research has focused on the health risks of PHEs bound to PM in landfill air. This systematic review aimed to examine PHEs, including Lead (Pb), Cadmium (Cd), Chromium (Cr), Arsenic (As), Nickel (Ni), and Zinc (Zn) bound with PM in landfill air and assess the health risk for workers and waste management personnel. The systematically search was made in different electronic databases. After the screening, 18 most relevant studied focused on PHEs bound PM in landfill air were selected. The data extraction analysis indicated that mean concentrations of Pb, Cd, Cr, As, Ni, and Zn in landfill air were 0.3037, 0.0941, 0.4093, 0.0221, 0.2768, and 0.7622μg/m3, respectively. Except for Pb, the concentrations of other PHEs bound to PM exceeded USEPA air quality standards. In addition, Non-carcinogenic risks from Cd, Cr, and Ni exposure exceeded permissible limits (HQ > 1), while As had an HQ value of 0.401. Carcinogenic risks from As, Cd, Ni, and Pb exposure were 1.31 × 10-5, 5.10 × 10-4, 3.51 × 10-5, and 2.03 × 10-6, respectively. Notably, the lifetime carcinogenic risk for workers exposed to Cr in polluted air (6.17 × 10-3) exceeded permissible limits (10-4 to 10-6). In conclusion, given the high carcinogenic and non-carcinogenic risks of some PHEs bound PM in landfills, it is necessary to conduct more research on the health effects of interaction with these PHEs bound PM on communities and the environment in different countries. Also, it is necessary to evaluate the role of different landfill operational activities on atmospheric dispersion of PHEs bound PM) in landfill air.

Assessment of heavy metal contamination in leafy vegetables: implications for public health and regulatory measures.

Heavy metal contamination in leafy vegetables poses significant health risks, highlighting the urgent need for stringent monitoring and intervention measures to ensure food safety and mitigate potential adverse effects on public health. This study investigates the levels of heavy metals, including cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), and copper (Cu), in locally grown and commercially available leafy vegetables, comparing them to the safety limits established by WHO/FAO. The results revealed that levels of Cd, Cr, Ni, and Pb in the vegetables exceeded WHO/FAO limits, while Zn and Cu remained within permissible bounds. Marketed vegetables exhibited higher metal concentrations than those from nearby farms. For Cu (0.114-0.289 mg/kg) and Zn (0.005-0.574 mg/kg), the daily intake of metals (DIM) was below the dietary intake (DI) and upper limit (UL). Cd's DIM (0.031-0.062 mg/kg) remained below the UL but exceeded the DI. Marketed kale and mint surpassed both DI and UL limits for Ni, while local produce only exceeded the DI. All vegetables had DIM below the DI, except for mint and kale. For Pb, every vegetable exceeded DI limits, with market samples contributing significantly. Cr's DIM ranged from 0.028 to 1.335 mg/kg, for which no set maximum daily intake exists. The health risk index (HRI) values for Zn, Cd, Cu, Ni, and Pb suggested potential health risks associated with leafy greens, while Cr's HRI was below 1. The study underscores the need for stringent monitoring and intervention measures to mitigate the health risks posed by heavy metal contamination in leafy vegetables. These findings suggest that consuming these leafy greens may put consumers at considerable risk for health problems related to Cd, Cu, Ni, Pb, and Zn exposure.

Protective effect of resveratrol on nickel-refining fumes-induced inflammatory damage.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1β, leading to cellular inflammation and reducing cell activity. Resveratrol (20 μmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1β overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Health risk assessment of heavy metals in soil and vegetables from major agricultural sites of Ohio and West Virginia

Contamination of soil and crops with heavy metals (HMs) poses a significant environmental challenge in the United States, while the status of metal contamination and associated health risks have been merely studied. Hence, this study aimed to assess metal contamination in major agricultural sites of Ohio and West Virginia, and evaluate the potential health risks associated with consuming metal-contaminated vegetables. Among the agricultural sites studied, Fe was the most predominant contaminant in all the sampling sites, ranging from 28,410 to 67,306 mg/kg of soil, exceeding the permissible limit of the US-EPA. Whereas Cd was the least contaminant, exceeding the permissible limit only in three sampling sites (ME1, ME3, and ME6), ranging from 0.13 to 2.91 mg/kg of soil. Interestingly, range of metals in vegetable samples were within the permissible limits. Principal component and hierarchical cluster analysis indicated the different natural and anthropogenic sources of metals in soil. In noncarcinogenic health risk assessment, the values of EDI, TEDI, THQ and HI levels for all the metals were lower than their daily uptake. However, CR and TCR assessment reveal significant risks associated with Ni exposure for both adults and children, with values of 3.487E-4 and 1.172E-3, and 5.362E-4 and 1.286E-3, respectively, within these agricultural sites. Therefore, regular monitoring of metal concentrations in soil and vegetables, as well as associated health risks, is strongly recommended to prevent potential health hazards in the future.

Occurrence and Exposure Assessment of Nickel in Zhejiang Province, China.

Nickel (Ni) is a silver-white metal with high antioxidative properties, often existing in a bivalent form in the environment. Despite being the fifth most abundant metal on Earth, anthropogenic activities, including industrial processes, have elevated Ni levels in environmental media. This study investigated Ni contamination in various food groups in Zhejiang Province, China, mainly focusing on Ni levels in beans, vegetables, aquatic foods, meat products, cereal products, and fruits. A total of 2628 samples were collected and analyzed. Beans exhibited the highest Ni content in all samples. The overall detection rate of Ni was 86.5%, with variation among food categories. For plant-origin foods, legumes had the highest Ni concentration while for animal-origin foods, shellfish showed the highest median Ni concentration. The results indicate generally acceptable Ni exposure levels among Zhejiang residents, except for children aged 0-6. Beans were identified as the primary contributor to high Ni exposure risk. The paper suggests monitoring Ni contamination in food, especially for vulnerable populations, and provides insights into exposure risks in different age groups.

Phytoplankton response to increased nickel in the context of ocean alkalinity enhancement

Abstract. Ocean alkalinity enhancement (OAE) is considered one of the most promising approaches to actively remove carbon dioxide (CO2) from the atmosphere by accelerating the natural process of rock weathering. This approach involves introducing alkaline substances sourced from natural mineral deposits, such as olivine, basalt, and carbonates or obtained from industrial waste products such as steel slag, into seawater and dispersing them over coastal areas. Some of these natural and industrial substances contain trace metals, which would be released into the oceans along with the alkalinity enhancement. The trace metals could serve as micronutrients for marine organisms at low concentrations but could potentially become toxic at high concentrations, adversely affecting marine biota. To comprehensively assess the feasibility of OAE, it is crucial to understand how the phytoplankton, which forms the base of marine food webs, responds to ocean alkalinization and associated trace metal perturbations. As one of the most abundant metals in OAE source materials, understanding the impacts of nickel (Ni) on the phytoplankton is critical for OAE assessment. In this study, we investigated the influence of nickel (Ni) on three representative phytoplankton species over a gradient of nine Ni concentrations (from 0 to 100 µmol L−1 with 12 µmol L−1 synthetic organic ligand). The impacts of elevated Ni varied among the tested phytoplankton species. The coccolithophore Emiliania huxleyi and the dinoflagellate Amphidinium carterae exhibited a growth rate inhibition of about 30 % and 20 %, respectively, at the highest Ni concentrations. The half maximal inhibitory concentration (IC50, at which the growth rate is inhibited by 50 %) of both species exceeded the tested range of Ni. This suggests that both species were only mildly affected by the elevated Ni concentrations. In contrast, the diatom Thalassiosira weissflogii displayed a considerably higher sensitivity to Ni, with a 60 % growth rate inhibition at the highest Ni concentration and an IC50 value of 63.9 µmol L−1. In conclusion, the variability in phytoplankton sensitivity to Ni exposure suggests that for OAE applications with Ni-rich materials caution is required and critical toxic thresholds for Ni must be avoided.

Microbial colony sequencing combined with metabolomics revealed the effects of chronic hexavalent chromium and nickel combined exposure on intestinal inflammation in mice

The pollution and toxic effects of hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] have become worldwide public health issues. However, the potential detailed effects of chronic combined Cr(VI) and Ni exposure on colonic inflammation in mice have not been reported. In this study, 16S rDNA sequencing, metabolomics data analysis, qPCR and other related experimental techniques were used to comprehensively explore the mechanism of toxic damage and the inflammatory response of the colon in mice under the co-toxicity of chronic hexavalent chromium and nickel. The results showed that long-term exposure to Cr(VI) and/or Ni resulted in an imbalance of trace elements in the colon of mice with significant inflammatory infiltration of tissues. Moreover, Cr(VI) and/or Ni poisoning upregulated the expression levels of IL-6, IL-18, IL-1β, TNF-α, IFN-γ, JAK2 and STAT3 mRNA, and downregulated IL-10 mRNA, which was highly consistent with the trend in protein expression. Combined with multiomics analysis, Cr(VI) and/or Ni could change the α diversity and β diversity of the gut microbiota and induce significant differential changes in metabolites such as Pyroglu-Glu-Lys, Val-Asp-Arg, stearidonic acid, and 20-hydroxyarachidonic acid. They are also associated with disorders of important metabolic pathways such as lipid metabolism and amino acid metabolism. Correlation analysis revealed that there was a significant correlation between gut microbes and metabolites (P < 0.05). In summary, based on the advantages of comprehensive analysis of high-throughput sequencing sets, these results suggest that chronic exposure to Cr(VI) and Ni in combination can cause microbial flora imbalances, induce metabolic disorders, and subsequently cause colonic damage in mice. These data provide new insights into the toxicology and molecular mechanisms of Cr(VI) and Ni.

Dynamic adaptation of the extremophilic red microalga Cyanidioschyzon merolae to high nickel stress

The order of Cyanidiales comprises seven acido-thermophilic red microalgal species thriving in hot springs of volcanic origin characterized by extremely low pH, moderately high temperatures and the presence of high concentrations of sulphites and heavy metals that are prohibitive for most other organisms. Little is known about the physiological processes underlying the long-term adaptation of these extremophiles to such hostile environments. Here, we investigated the long-term adaptive responses of a red microalga Cyanidioschyzon merolae, a representative of Cyanidiales, to extremely high nickel concentrations. By the comprehensive physiological, microscopic and elemental analyses we dissected the key physiological processes underlying the long-term adaptation of this model extremophile to high Ni exposure. These include: (i) prevention of significant Ni accumulation inside the cells; (ii) activation of the photoprotective response of non-photochemical quenching; (iii) significant changes of the chloroplast ultrastructure associated with the formation of prolamellar bodies and plastoglobuli together with loosening of the thylakoid membranes; (iv) activation of ROS amelioration machinery; and (v) maintaining the efficient respiratory chain functionality. The dynamically regulated processes identified in this study are discussed in the context of the mechanisms driving the remarkable adaptability of C. merolae to extremely high Ni levels exceeding by several orders of magnitude those found in the natural environment of the microalga. The processes identified in this study provide a solid basis for the future investigation of the specific molecular components and pathways involved in the adaptation of Cyanidiales to the extremely high Ni concentrations.

Toxic effects of nickel on tolerance and regeneration in the freshwater shrimp Neocaridina davidi

Heavy metals cause environmental pollution and produce toxic effects on organisms. Nickel (Ni) is a common metallic pollutant of aquatic ecosystems and potentially can produce multifarious changes in the body of aquatic organisms. The average nickel content in rivers is about 0.7 μg/l. As a result, the homeostasis of the affected organism is disturbed, and processes that can counteract the changes are activated. To better understand the effects of Ni in the freshwater environment and its fauna, it is important to establish whether all changes caused in cells and tissues by Ni exposure are reversible when the animal returns to the non-polluted environment. Thus, the main aim of the study was to analyze changes that occur after Ni exposure and after it is returned to non-contaminated water at various levels of the animal’s body. The freshwater shrimp Neocaridina davidi (Crustacea) was selected as the subject of the study. As the organ for studies, we chose the midgut because it is a barrier against stressors that enter the organism. A concentration of 3.63 mg Ni/l was selected for the experiment, at which approximately 50% mortality of the population was observed after 14 days. The midgut was analyzed using light and transmission electron microscopy (TEM), confocal microscopy, and flow cytometry for qualitative and quantitative results. When the organisms were transferred to clean water, a prolong exposure resulted in a decrease in the values of the analyzed parameters (e.g. ROS, cell death, etc.) proportional to the purification time. The recovery time was insufficient to return to control values in most analyzed groups. Nevertheless, the occurrence of regenerative changes suggests that freshwater shrimps are relatively tolerant to nickel, when the exposure time is short and the recovery time is long.

Chronic nickel exposure alters extracellular vesicles to mediate cancer progression via sustained NUPR1 expression

Cancer cells release extracellular vesicles (EVs) that participate in altering the proximal tumor environment and distal tissues to promote cancer progression. Chronic exposure to nickel (Ni), a human group I carcinogen, results in epigenetic changes that promotes epithelial to mesenchymal transition (EMT). Cells that undergo EMT demonstrate various molecular changes, including elevated levels of the mesenchymal cadherin N-cadherin (N-CAD) and the transcription factor Zinc finger E-box binding homeobox 1 (ZEB1). Moreover, the molecular changes following EMT induce changes in cellular behavior, including anchorage-independent growth, which contributes to cancer cells detaching from tumor bulk during the metastatic process. Here, we present data demonstrating that EVs from Ni-exposed cells induce EMT in recipient BEAS-2B cells in the absence of Ni. Moreover, we show evidence that the EVs from Ni-altered cells package the transcription factor nuclear protein 1 (NUPR1), a transcription factor associated with Ni exposure and cancer progression. Moreover, our data demonstrates that the NUPR1 in the EVs becomes part of the recipient cell proteomic milieu and carry the NUPR1 to the nuclear space of the recipient cell. Interestingly, knockdown of NUPR1 in Ni-transformed cells suppressed NUPR1 packaging in the EVs, and nanoparticle tracking analysis (NTA) demonstrated decreased EV release. Reduction of NUPR1 in EVs resulted in diminished EMT capacity that resulted in decreased anchorage independent growth. This study is the first to demonstrate the role of NUPR1 in extracellular vesicle-mediate cancer progression.

The effect of geraniol on nickel-induced embryotoxicity and cardiotoxicity in rats.

Nickel (Ni), commonly-used heavy metals in industrial activities, can lead to embryo and organ toxicity, especially cardiovascular damage. Geraniol (GER) has various beneficial effects such as anti-oxidant, anti-inflammatory, anti-tumor, anti-ulcer, anti-microbial, and neuroprotective activities. The objective of this study was to investigate the effect of GER on Ni-induced embryotoxicity and cardiotoxicity in rats. 40 mother Wistar rats were randomly divided into five groups: Control, GER 250, Ni, Ni + GER 100, and Ni + GER 250. On the 20th day of pregnancy, the animals were sacrificed and fetuses along with blood and tissue samples were collocated for morphological, serological, biochemical, and histopathologic analysis. Morphological assessments revealed GER's capacity to mitigate the incomplete ossification of fetal skeletons, indicating a potential safeguarding against the impact of Ni-induced embryotoxicity. Serological and biochemical analyses further affirm GER's role, with noteworthy reductions in cardiac injury markers, such as CRP, CKMB, CPK, LDH, and troponin, in response to GER administration, thereby suggesting its cardioprotective potential. Moreover, treatment with GER 250 could significantly reduce the level of MDA and increase the level of TAC compared to the Ni group. Histopathological examinations corroborated these findings, underscoring GER's ability to counteract cardiac injury and diminish structural damage in affected tissue. These multidimensional analyses indicate the protective prowess of GER against Ni-induced embryotoxic and cardiotoxic effects, shedding light on its potential therapeutic significance in combating adverse impacts stemming from Ni exposure.

Isolated and combined effects of cobalt and nickel on the microalga Raphidocelis subcapitata.

Aquatic organisms are exposed to several compounds that occur in mixtures in the environment. Thus, it is important to investigate their impacts on organisms because these combined effects can be potentiated. Cobalt (Co) and nickel (Ni) are metals that occur in the environment and are used in human activities. To the best of our knowledge, there are no studies that investigated the combined effects of these metals on a freshwater Chlorophyceae. Therefore, this study analyzed the isolated and combined effects of Co and Ni in cell density, physiological and morphological parameters, reactive oxygen species (ROS), carbohydrates and photosynthetic parameters of the microalga Raphidocelis subcapitata. Data showed that Co affected the cell density from 0.25 mg Co L-1; the fluorescence of chlorophyll a (Chl a) (0.10 mg Co L-1); ROS production (0.50 mg Co L-1), total carbohydrates and efficiency of the oxygen evolving complex (OEC) at all tested concentrations; and the maximum quantum yield (ΦM) from 0.50 mg Co L-1. Ni exposure decreased ROS and cell density (0.35 mg Ni L-1); altered Chl a fluorescence and carbohydrates at all tested concentrations; and did not alter photosynthetic parameters. Regarding the Co-Ni mixtures, our data best fitted the concentration addition (CA) model and dose-ratio dependent (DR) deviation in which synergism was observed at low doses of Co and high doses of Ni and antagonism occurred at high doses of Co and low doses of Ni. The combined metals affected ROS production, carbohydrates, ΦM, OEC and morphological and physiological parameters.

Effects of Cadmium and Nickel on Embryonic Development of Fish: A Review

In fish embryos, a variety of abnormalities have been found, including stunted growth, a reduced survival rate, and aberrant development. One plausible explanation is that early embryonic stages are more sensitive. Embryonic studies provide additional information regarding the various impacts of heavy metals on fish, but information on larval abnormalities caused by waterborne metals is lacking. It is found that cadmium (Cd) causes a decrease in thyroid hormone levels as well as a disruption in fish growth hormone expression. Similarly, negative health effects have been documented as a result of nickel (Ni) exposure. Some toxic effects on organs, skin irritation, skin itches or blisters and allergic reactions may occur as a result of Ni exposure. This review study focuses on the impacts of Cd and Ni, on the embryonic development of different fish species. The evidence on abnormalities in fish larvae caused by Cd and Ni was also provided in text.