Metal-induced Oxidative Stress Research Articles

Comparative transcriptomics provides insight into molecular mechanisms of zinc tolerance in the ectomycorrhizal fungus Suillus luteus.

Zinc (Zn) is a major soil contaminant and high Zn levels can disrupt growth, survival, and reproduction of fungi. Some fungal species evolved Zn tolerance through cell processes mitigating Zn toxicity, though the genes and detailed mechanisms underlying mycorrhizal fungal Zn tolerance remain unexplored. To fill this gap in knowledge, we investigated the gene expression of Zn tolerance in the ectomycorrhizal fungus Suillus luteus. We found that Zn tolerance in this species is mainly a constitutive trait that can also be environmentally dependent. Zinc tolerance in S. luteus is associated with differences in expression of genes involved in metal exclusion and immobilization, as well as recognition and mitigation of metal-induced oxidative stress. Differentially expressed genes were predicted to be involved in transmembrane transport, metal chelation, oxidoreductase activity, and signal transduction. Some of these genes were previously reported as candidates for S. luteus Zn tolerance, while others are reported here for the first time. Our results contribute to understanding the mechanisms of fungal metal tolerance and pave the way for further research on the role of fungal metal tolerance in mycorrhizal associations.

Inoculation of heavy metal resistant bacteria alleviated heavy metal-induced oxidative stress biomarkers in spinach (Spinacia oleracea L.)

Most vegetable crops are severely affected by the uptake of heavy metals from the soil. Heavy metals in vegetable bodies generate reactive oxygen species (ROS) that unbalance the antioxidant defense system. This study was initiated to determine the physiological and biochemical characteristics of spinach plants grown on soil contaminated with heavy metals and responding to Bacillus cereus and Bacillus aerius were isolated from soil contaminated with heavy metals. Heavy metal contamination led to a significant reduction in seed germination, seedling biomass, protein, and total nitrogen content of spinach plants grown in contaminated soils compared to control soils. In contrast, a significant increase in the content of metallothioneins and antioxidant enzymes was observed. Plants inoculated with B. cereus and B. aerius significantly reduced the oxidative stress induced by heavy metals by improving seed germination (%), seedling growth, nitrogen, and protein content. The content of metallothioneins and the activities of antioxidant enzymes were reduced in spinach plants grown from seeds inoculated with bacterial strains. In addition, plants inoculated with, B. cereus and B. aerius showed greater stomata opening than plants grown on soil contaminated with heavy metals, whose stomata were almost closed. These results suggested that both bacterial strains enhanced plant growth by reducing oxidative stress caused by metals.

The Post-Transcriptional Regulatory Protein CsrA Amplifies Its Targetome through Direct Interactions with Stress-Response Regulatory Hubs: The EvgA and AcnA Cases.

Global rewiring of bacterial gene expressions in response to environmental cues is mediated by regulatory proteins such as the CsrA global regulator from E. coli. Several direct mRNA and sRNA targets of this protein have been identified; however, high-throughput studies suggest an expanded RNA targetome for this protein. In this work, we demonstrate that CsrA can extend its network by directly binding and regulating the evgA and acnA transcripts, encoding for regulatory proteins. CsrA represses EvgA and AcnA expression and disrupting the CsrA binding sites of evgA and acnA, results in broader gene expression changes to stress response networks. Specifically, altering CsrA-evgA binding impacts the genes related to acidic stress adaptation, and disrupting the CsrA-acnA interaction affects the genes involved in metal-induced oxidative stress responses. We show that these interactions are biologically relevant, as evidenced by the improved tolerance of evgA and acnA genomic mutants depleted of CsrA binding sites when challenged with acid and metal ions, respectively. We conclude that EvgA and AcnA are intermediate regulatory hubs through which CsrA can expand its regulatory role. The indirect CsrA regulation of gene networks coordinated by EvgA and AcnA likely contributes to optimizing cellular resources to promote exponential growth in the absence of stress.

Upregulation of antioxidant enzymes contribute to the elevated tolerance of Juncus acutus offspring from metal contaminated environments

Long-term environmental exposure to metals e.g. zinc (Zn), may allow saltmarsh halophytes to develop metal tolerance to improve the chance of survival of their progeny in future metal-contaminated scenarios. Juncus acutus seeds were collected from mature parents (F0) inhabiting a legacy Zn-contaminated location (Cockle Creek) and an uncontaminated reference location (Swansea) of Lake Macquarie, NSW, Australia. Seeds (J. acutus) were exposed to Zn (0.00 mM (control), 0.01 mM (effective concentration, EC10) and 0.74 mM (EC50)) and resultant germinants (F1) were allowed to grow until 15 days. Seedling growth parameters i.e. biomass, root length and 1st leaf length, and seedling biochemical responses i.e. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) antioxidant enzyme activity and lipid peroxidation products, malondialdehyde (MDA), were examined in order to assess if enzymes may be implicated in conferring tolerance to the offspring of metal-exposed parents. Control locations exhibited significantly greater declines in biomass and root length with Zn dose compared to seed from contaminated locations, suggesting F1 offspring from contaminated parents were conferred tolerance to Zn. Furthermore, significant upregulation of CAT and GPx enzymes were evident in the seedlings derived from parents of contaminated locations. These are the antioxidative enzymes responsible for minimizing metal-induced oxidative stress, and may, in part, be responsible for increasing seedling fitness and observed tolerance.

NMR- and HRMS-based untargeted metabolomic study of metal-stressed Euglena gracilis cells

Environmental contamination is an increasing problem and one of the main threats to human health. While euglenoids have been shown to tolerate high levels of metals, little is known about the metabolic mechanisms at play. To address this gap, Euglena gracilis cells in the mixotrophic exponential phase were exposed to high levels of cadmium (Cd), cobalt (Co), or copper (Cu) (2.7–190.7 mg L−1) and the cellular metabolic profiles were explored using a multi-pronged untargeted approach. The combined application of proton nuclear magnetic resonance (1H NMR) and high-resolution mass spectrometry (HRMS) expanded the coverage of detected metabolites by 38–58 % using the computational platform Pathos and the metabolite databases KEGG, Metlin, and Chenomx. Only 3 % of the identified metabolites were found to be common to 1H NMR and HRMS. This low overlap indicates that the two methods complement each other, with each method uncovering a unique set of metabolites. Although four metabolic pathways including purine metabolism, alanine, aspartate, and glutamate metabolism, and the citrate cycle were common to all metal treatments, sixteen metabolic pathways were metal-specific. Notably, the metabolic alterations induced by Cd and Co differed from each other and the control, while the metabolic profile of Cu-treated cells resembled the control more closely. Unlike Co which showed a broad impact on Euglena gracilis metabolism, the stress induced by Cd and Cu exposure seems to target more the amino sugar production and the chlorophyll machinery, respectively. The observed metabolic alterations in response to various metals highlight a potential correlation with the generation of reactive oxygen species (ROS). Together these results contribute to a better understanding of cellular toxicity and the impacts of metal-induced oxidative stress in Euglena gracillis cells.

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects

Ethnopharmacological relevanceFraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. Aim of the studyThe objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. Materials and methodsThe maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. ResultsLC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. ConclusionFE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Unraveling assemblage of microbial community dwelling in Dabaoshan As/Pb/Zn mine-impacted area: A typical mountain mining area of South China

Microbial community assemblage includes microorganisms from the three domains including Bacteria, Archaea, and Eukarya (Fungi), which play a crucial role in geochemical cycles of metal(loid)s in mine tailings. Mine tailings harbor vast proportions of metal(loid)s, representing a unique source of co-contamination of metal(loid)s that threaten the environment. The elucidation of the assembly patterns of microbial communities in mining-impacted ecospheres has received little attention. To decipher the microbial community assembly processes, the microbial communities from the five sites of the Dabaoshan mine-impacted area were profiled by the MiSeq sequencing of 16S rRNA (Bacteria and Archaea) genes and internal transcribed spacers (Fungi). Results indicated that the coexistence of 31 bacterial, 10 fungal, and 3 archaeal phyla, were mainly dominated by Mucilaginibacter, Cladophialophora, and Candidatus Nitrosotalea, respectively. The distribution of microorganisms was controlled by deterministic processes. The combination of Cu, Pb, and Sb was the main factor explaining the structure of microbial communities. Functional predicting analysis of bacteria and archaea based on the phylogenetic investigation of communities by reconstruction of unobserved states analyses revealed that the metabolic pathways related to arsenite transporter, arsenate reductase, and FeS cluster were important for metal detoxification. Furthermore, the ecological guilds (pathogens, symbiotrophs, and saprotrophs) of fungal communities explained 44.5 % of functional prediction. In addition, metal-induced oxidative stress may be alleviated by antioxidant enzymes of fungi communities, such as catalase. Such information provides new insights into the microbial assembly rules in co-contaminated sites.

Assessment of toxic metal pollution in Yueqing Bay and the extent of metal-induced oxidative stress in Tegillarca granosa raised in this water

Yueqing Bay is an important economic shellfish culture zone in Zhejiang Province, China. However, increased pollution in the water caused by toxic metals has led to the bioaccumulation of toxic metals in cockles such as Tegillarca granosa, and the consequence of toxic metal-associated toxicity in these animals. This study aimed to assess the concentration of toxic metals in the water and sediment in four different sites (Baisha, Qingjiang, Nanyue, and Wengyang) within Yueqing Bay and to evaluate the extent of metal bioaccumulation in T. granosa raised in the aquaculture farms located within the four sites, as well as the changes in biomarkers in T. granosa in response to the metals. The assessment was carried out at two different times of the year, January and July. The water and sediment samples taken from the aquaculture farms in Baisha (S1), Qingjiang (S2) and Nanyue (S3) were found to have a comprehensive toxic metal pollution index (Pc) <1, indicating that these farms were not polluted. However, the water and sediment samples taken from the aquaculture farm in Wengyang (S4) had a Pc between 1 and 2, indicating mild toxic metal pollution. The edible risk assessments (HQ) of T. granosa in all four farms were <1, and therefore, these cockles could be considered safe for human consumption. The toxic metal enrichment in T. granosa exhibited a strong correlation with the toxic metal content in the sediment. In all four farms, CAT and SOD activity levels in the visceral mass of T. granosa were higher than those found in the foot, and a significantly higher level of CAT activity was detected in July compared with January. Similarly, MDA and H2O2 contents in the visceral mass were also higher in July than in January. Tegillarca granosa individuals taken from S4 and S3 farms exhibited significantly higher levels of metallothionein (MT) mRNA and MDA compared with individuals from S1 and S2 farms. Furthermore, the levels of MDA and MT mRNA showed significant positive correlations with Cd, Cr, Hg, and Cu. Elevation of lipid peroxidation in these cockles coincided with increasing levels of endogenous antioxidants. The visceral mass of T. granosa and its MDA level could be used as a tissue indicator and a biochemical marker, respectively, for detecting toxic metal pollution. MT mRNA might also be used as a molecular marker of toxic metal pollution. The integrated biomarker response version 2 (IBRv2) values of the four aquaculture farms in Yueqing Bay showed the order S4 > S3 > S2 > S1, indicating that S4 had the most serious metal-induced stress. Furthermore, the IBRv2 values correlated with the Nemerow composite index (Pc) for all the cockles examined. Thus, as far as the contamination of aquaculture farms in Yueqing Bay by toxic metals is concerned, the aquaculture farm in Wengyang (S4) was mildly contaminated by toxic metals. However, the contamination was relatively low, presenting a low risk for the local population of T. granosa.

Remediation of soil polluted with Pb and Cd and alleviation of oxidative stress in Brassica rapa plant using nanoscale zerovalent iron supported with coconut-husk biochar

Accumulation of toxic elements by plants from polluted soil can induce the excessive formation of reactive oxygen species (ROS), thereby causing retarded plants' physiological attributes. Several researchers have remediated soil using various forms of zerovalent iron; however, their residual impacts on oxidative stress indicators and health risks in leafy vegetables have not yet been investigated. In this research, nanoscale zerovalent iron supported with coconut-husk biochar (nZVI-CHB) was synthesized through carbothermal reduction process using Fe2O3 and coconut-husk. The stabilization effects of varying concentrations of nZVI-CHB and CHB (250 and 500 mg/kg) on cadmium (Cd) and lead (Pb) in soil were analyzed, and their effects on toxic metals induced oxidative stress, physiological properties, and antioxidant defence systems of the Brassica rapa plant were also checked. The results revealed that the immobilization of Pb and Cd in soil treated with CHB was low, leading to a higher accumulation of metals in plants grown. However, nZVI-CHB could significantly immobilize Pb (57.5–62.12%) and Cd (64.1–75.9%) in the soil, leading to their lower accumulation in plants below recommended safe limits and eventually reduced carcinogenic risk (CR) and hazard quotient (HQ) for both Pb and Cd in children and adults below the recommended tolerable range of <1 for HQ and 10−6 – 10−4 for CR. Also, a low dose of nZVI-CHB significantly mitigated toxic metal-induced oxidative stress in the vegetable plant by inhibiting the toxic metals uptake and increasing antioxidant enzyme activities. Thus, this study provided another insightful way of converting environmental wastes to sustainable adsorbents for soil remediation and proved that a low-dose of nZVI-CHB can effectively improve soil quality, plant physiological attributes and reduce the toxic metals exposure health risk below the tolerable range.

Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson's Disease.

Parkinson's disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of α-synuclein is thought to propagate from the enteric nervous system to the central nervous system. The pathogenesis in sporadic PD remains unknown. However, many reports indicate various etiological factors, such as oxidative stress, inflammation, α-synuclein toxicity and mitochondrial impairment, drive neurodegeneration. Exposure to heavy metals contributes to these etiopathogenesis and increases the risk of developing PD. Metallothioneins (MTs) are cysteine-rich metal-binding proteins; MTs chelate metals and inhibit metal-induced oxidative stress, inflammation and mitochondrial dysfunction. In addition, MTs possess antioxidative properties by scavenging free radicals and exert anti-inflammatory effects by suppression of microglial activation. Furthermore, MTs recently received attention as a potential target for attenuating metal-induced α-synuclein aggregation. In this article, we summarize MTs expression in the central and enteric nervous system, and review protective functions of MTs against etiopathogenesis in PD. We also discuss neuroprotective strategies for the prevention of central dopaminergic and enteric neurodegeneration by targeting MTs. This review highlights multifunctional MTs as a target for the development of disease-modifying drugs for PD.

Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection

Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutrients such as iron, copper, zinc, and manganese play various roles in human tissues and their imbalance in blood can impact immune responses against pathogens including SARS CoV-2. We hypothesized that alteration of free metal ions during infection and metal-catalyzed oxidation plays a critical role towards pathogenesis after infection. We analyzed convalescent and hospitalized COVID-19 patient plasma using orthogonal analytical techniques to determine redox active metal concentrations, overall protein oxidation, oxidative modifications, and protein levels via proteomics to understand the consequences of metal-induced oxidative stress in COVID-19 plasma proteins. Metal analysis using ICP-MS showed significantly greater concentrations of copper in COVID-19 plasma compared to healthy controls. We demonstrate significantly greater total protein carbonylation, other oxidative modifications, and deamidation of plasma proteins in COVID-19 plasma compared to healthy controls. Proteomics analysis showed that levels of redox active proteins including hemoglobulin were elevated in COVID-19 plasma. Molecular modeling concurred with potential interactions between iron binding proteins and SARS CoV-2 surface proteins. Overall, increased levels of redox active metals and protein oxidation indicate that oxidative stress-induced protein oxidation in COVID-19 may be a consequence of the interactions of SARS-CoV-2 proteins with host cell metal binding proteins resulting in altered cellular homeostasis.

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study.

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies.

Redox Status, Immune Alterations, Histopathology, and Micronuclei Induction in Labeo rohita Dwelling in Polluted River Water

In this study, we measured various parameters of oxidative stress, immune response, and abnormalities in the erythrocyte nucleus of Labeo rohita inhabiting the polluted Kshipra River, India. The river water contains heavy metals in this order: Ni > Fe > Cd > Cr > Mn > Zn > Cu. Fe showed the highest accumulation in gills, liver, and gut, whereas Ni (gills and gut) and Cd (liver) were lowest accumulated. The superoxide dismutase (SOD) and catalase (CAT) were found to be increased significantly (p < 0.05) in the gills (SOD: 211%; CAT: 150%), liver (SOD: 447%; CAT: 304%), and gut (SOD: 98.11%; CAT: 58.69%) in comparison with the reference fish. However, glutathione S transferase (GST) showed significantly (p < 0.05) higher activity in the gills (25.5%) but lower activity in the liver (- 49.22%) and the gut (- 30.57%). Moreover, reduced glutathione (GSH) decreased significantly (p < 0.05) in the gills (- 46.66%), liver (- 33.20%), and gut (- 39.87%). Despite the active response of the antioxidant enzymes, the highest lipid peroxidation was observed in the liver (463%). The effect of heavy metals was also observed on the immunity of the fish, causing immunosuppression as evident by significantly (p < 0.05) lower values of acid phosphatase (- 50%), myeloperoxidase (- 48.33%), and nitric oxide synthase (- 50%) in serum. Histopathological findings showed gill lamellae shortening, hyperplasia, club-shaped lamellar tip in exposed gills and necrosis, vacuolization, and pyknosis in the exposed liver. Furthermore, polluted river water was also found to induce micronuclei (2.1%) and lobed nuclei (0.72%) in erythrocytes (0.65%). These results indicate the potential of heavy metal-induced oxidative stress and other forms of stress in inhabiting fish, highlighting the need to control the pollution of this river water.

Characterization of Metallic Off-Flavors in Drinking Water: Health, Consumption, and Sensory Perception

Characterization of taste- and flavor-producing metals, namely iron and copper, in drinking water is a multifaceted subject. Both metals are essential nutrients, can be toxic, and are known to produce unpleasant tastes and flavor sensations in drinking water. Ingestion of trace metal contaminants through drinking water is a probable source of human exposure. Biochemical mechanisms of metallic flavor perception have been previously described; however, less is known about how variations in salivary constituents might impact individuals' sensitivities to metallic flavors and beverage consumption behaviors. This research presents findings from in vitro experiments, using artificial human saliva, to better understand the role of salivary lipids and proteins on metallic flavor production as measured by biomarkers of metal-induced oxidative stress. The results indicate that metal-induced lipid oxidation, as measured by thiobarbituric acid reactive substances (TBARS), is dominated by salivary proteins, is slightly inhibited in the presence of salivary nitrite, and is detectable by the TBARS method at and above respective concentrations of 9 µM (0.5 mg/L) and 90 µM (5 mg/L), which are both above the aesthetic standards for iron (0.3 mg/L) and copper (1.0 mg/L) in drinking water. Preliminary study with human subjects indicated that reduction in metallic flavor sensitivity, as measured by the best estimate flavor threshold for ferrous iron among 33 healthy adults aged 19-84 years old (22 females), corresponded with reduced drinking water consumption and increased caloric beverage intake among older subjects (>60 years), as determined by a validated self-reported beverage intake questionnaire. These findings provide insights for further research to examine how salivary constituents can impact humans' sensory abilities in detecting metallic off-flavors in water, and how reduced metallic flavor sensitivity may influence beverage choices and drinking water consumption.

Integration of Transcriptome and Metabolome Analyses Reveals the Mechanistic Basis for Cadmium Accumulation in Maize.

Cadmium (Cd) pollution in soil has become a major environmental issue worldwide. However, the underlying molecular mechanism of low grain-Cd accumulation (GCA) in maize is still largely unknown. Herein, we report the mechanistic basis for low GCA in maize by a multiomics approach. The low GCA genotype L63 showed normal vacuolar formation and a lower capacity of xylem loading of Cd than the high-accumulator L42 under Cd stress. Transcriptomic sequencing identified 84 low-GCA-associated genes which are mainly involved in the S-adenosylmethionine (SAM) cycle, metal transport, and vacuolar sequestration. A metabolome analysis revealed that L63 plants had a more active SAM cycle and a greater capacity for terpenoid synthesis and phenylalanine metabolism than L42. Combining the analysis of transcriptome and metabolome characterized several genes as key genes involved in the determination of Cd accumulation. Our study identifies a mechanistic basis for low Cd accumulation in maize grains and provides candidate genes for genetic improvement of crops.

Effects of fungal seed endophyte FXZ2 on Dysphania ambrosioides Zn/Cd tolerance and accumulation

Metal-induced oxidative stress in contaminated soils affects plant growth. In the present study, we evaluated the role of seed endophyte FXZ2 on Dysphania ambrosioides Zn/Cd tolerance and accumulation. A series of pot experiments were conducted under variable Zn (500, 1,000, and 1,500 mg kg–1) and Cd (5, 15, 30, and 60 mg kg–1). The results demonstrated that FXZ2-inoculation significantly enhanced the growth of D. ambrosioides and improved its chlorophyll and GSH content. In the rhizosphere, FXZ2 inoculation changed the chemical speciation of Zn/Cd and thus affected their uptake and accumulation in host plants. The exchangeable and carbonate-bound fractions (F1 + F2) of Zn decreased in the rhizosphere of FXZ2-inoculated plants (E+) as compared to non-inoculated plants (E-) under Zn stress (500 and 1,000 mg kg–1), correspondingly, Zn in the shoots of E+ decreased (p < 0.05). However, at Cd stress (30 and 60 mg kg–1), the F1 + F2 fractions of Cd in E+ rhizospheric soils increased; subsequently, Cd in the shoots of E+ increased (p < 0.05). FXZ2 could exogenously secrete phytohormones IAA, GA, and JA. The study suggests that seed endophyte FXZ2 can increase Zn/Cd tolerance of host plant by altering Zn/Cd speciation in rhizospheric soils, as well as exogenous production of phytohormones to promote growth, lowering oxidative damage while enhancing antioxidant properties. For Zn/Cd accumulation, it has opposite effects: Zn uptake in E+ plants was significantly (p < 0.05) decreased, while Cd accumulation in E+ plants was significantly (p < 0.05) increased. Thus, FXZ2 has excellent application prospects in Cd phytoextraction and decreasing Zn toxicity in agriculturally important crops.

Correlative study on heavy metal-induced oxidative stress and hypertension among the rural population of Malwa Region of Punjab, India.

Heavy metal-induced toxicity contributes to the progression of various metabolic disorders and possible mechanisms involved in disease progression are not well established. In this study, the correlation of heavy metal exposure and hypertension have been demonstrated. The results showed that in hypertensive subjects, the lipid profiles (triglycerides, LDL-C, HDL-C, and total cholesterol) and cardiac markers (CK-MB and LDH) were altered abruptly. As a consequence of heavy- induced oxidative stress, the oxidants (TBARS and protein carbonyls) and antioxidants (SOD, GSH, and TAC) were significantly increased and decreased, respectively in hypertensionsubjects. The concentrations of heavy metals (Pb, Cd, and As) exceeded the permissible limits in hypertensive subjects. The Nrf-2 genotyping indicated that heavy metals may induce mutations at molecular level. The results of correlation analysis revealed thatthe heavy metals interact with cellular components and interfere with metabolic processes which thenresults in disturbed lipid profile, enhanced oxidative stress, and reduced antioxidant status. The current study systematically estimated the association of hair and nail heavy metal concentrations with hypertension among the population residing in the Malwa region of Punjab. The proposed study highlighted that heavy metals act as a silent risk factor in the hypertension progression in the population of Malwa region. Future studies are required to confirm current findings and further scrutinize the effect of heavy metals exposure in early adulthood, early, and late mid-life to develop metabolic complications such as hypertension.

Therapeutic Strategies and Metal-Induced Oxidative Stress: Application of Synchrotron Radiation Microbeam to Amyotrophic Lateral Sclerosis in the Kii Peninsula of Japan.

A series of extensive gene-environment studies on amyotrophic lateral sclerosis (ALS) and Parkinsonism–dementia complex (PDC) in Guam Island, USA, and the Kii Peninsula of Japan, including Auyu Jakai, West New Guinea, have led us to hypothesize that a prolonged low calcium (Ca) and magnesium (Mg) intake, especially over generation, may cause oxidative stress to motor and nigral neurons by an increased uptake of environment metallic elements, i.e., aluminum (Al), manganese (Mn), and iron (Fe). Otherwise, 5–10% of total ALS cases are familial ALS (fALS), of which 20% of the fALS cases linked to a point mutation of Cu/Zn superoxide dismutase (SOD1). In the vicinity of the Kii Peninsula, about 7% of the ALS cases are also linked to the SOD1 mutation. Using synchrotron radiation (SR) microbeam, conglomerate inclusion (SOD1 aggregates) within a spinal motor neuron of the fALS case in the vicinity revealed a loss of copper (Cu) in contrast to extremely high contents of Zinc (Zn) and Ca. That means an exceptionally low Cu/Zn ratio with an increased Ca content, indicating the abnormalities of the active site of SOD1 protein of the fALS. Furthermore, sALS in the southernmost high incidence areas of the Kii Peninsula showed a low Cu/Zn ratio within a motor neuron, suggesting a fragility of SOD1 proteins. From the perspective of gene–environment interactions, the above two research trends may show a common oxidative stress underlying the neuronal degenerative process of ALS/PDC in the Kii Peninsula of Japan. Therefore, it is a crucial point for the prospect of therapeutic strategy to clarify a role of transition metals in the oxidative process in both ALS/PDC, including ALS elsewhere in the world. This paper reviews a history of the genetic epidemiological studies, especially from the aspect of gene–environment interaction, on ALS/PDC in the Kii and Guam high incidence foci and the results of a series of analytical research on trace metallic elements within neurons of both sALS and fALS cases, especially using a synchrotron radiation (SR) microbeam of Spring-8 and Photon Factory of Japan. The SR microbeam is an ideal X-ray source, which supplies an extremely high brilliance (high-intensity photon) and tunability (energy variability) to investigate trace metallic elements contained in biological specimens at the cellular level, even more without any damages. This research will provide a valuable information about the mechanism of oxidative stress involved in neuronal cell death in ALS and related neurodegenerative disorders. To elucidate the physicochemical mechanism of the oxidative process in neuronal degeneration, it will shed a new light on the therapeutic strategies for ALS/PDC in near future.

Anthropogenic Zinc Exposure Increases Mortality and Antioxidant Gene Expression in Monarch Butterflies with Low Access to Dietary Macronutrients.

Biologists seek to understand why organisms vary in their abilities to tolerate anthropogenic contaminants, such as heavy metals. However, few studies have considered how tolerance may be affected by condition‐moderating factors such as dietary resource availability. For instance, the availability of crucial limiting macronutrients, such as nitrogen and phosphorous, can vary across space and time either naturally or due to anthropogenic nutrient inputs (e.g., agricultural fertilizers or vehicle emissions). Organisms developing in more macronutrient‐rich environments should be of higher overall condition, displaying a greater ability to tolerate metal contaminants. In monarch butterflies (Danaus plexippus), we factorially manipulated dietary macronutrient availability and exposure to zinc, a common metal contaminant in urban habitats that can be toxic but also has nutritional properties. We tested whether (1) the ability to survive zinc exposure depends on dietary macronutrient availability and (2) whether individuals exposed to elevated zinc levels display higher expression of antioxidant genes, given the roles of antioxidants in combatting metal‐induced oxidative stress. Exposure to elevated zinc reduced survival only for monarchs developing on a low‐macronutrient diet. However, for monarchs developing on a high‐macronutrient diet, elevated zinc exposure tended to increase survival. In addition, monarchs exposed to elevated zinc displayed higher expression of antioxidant genes when developing on the low‐macronutrient diet but lower expression when developing on the high‐macronutrient diet. Altogether, our study shows that organismal survival and oxidative stress responses to anthropogenic zinc contamination depend on the availability of macronutrient resources in the developmental environment. In addition, our results suggest the hypothesis that whether zinc acts as a toxicant or a nutrient may depend on macronutrient supply. Environ Toxicol Chem 2022;41:1286–1296. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Heavy metal-induced oxidative stress and alteration in secretory proteins in yeast isolates.

In the recent years, yeasts have evolved as potent bioremediative candidates for the detoxification of xenobiotic compounds found in the natural environment. Candida sp. are well-studied apart from Saccharomyces sp. in heavy metal detoxification mechanisms. In the current study, Candida parapsilosis strain ODBG2, Candida sp. strain BANG3, and Candida viswanathii strain ODBG4 were isolated from industrial effluents and contaminated ground water, and were studied for their metal tolerance. Among these three isolates, the metal tolerance was found to be more towards Lead (Pb 2mM), followed by Cadmium (Cd 1.5mM) and Chromium [Cr(VI), 1mM]. On further exploring the involvement of primary defensive enzymes in these isolates towards metal tolerance, the anti-oxidative enzyme superoxide dismutase was found to be prominently high (25% with respect to the control) during first 24h of metal-isolate interaction. The Catalase enzyme assay was observed to have increased enzyme activity at 48h. It also triggered the activity of peroxidases, which lead to the increase in reduced glutathione in the organism by 0.87-1.9-fold as a metal chelator and also as a second-line defensive molecule. The exoproteome profile showed the early involvement (exponential growth phase) of secreted proteins (low-molecular-weight) of about ~ 40-45kDa under Cd and Pb stress (0.5mM). The exoproteome profiling under heavy metal stress in Candida parapsilosis strain ODBG2 and Candida viswanathii strain ODBG4 is the first report.