Doses Of Arsenic Research Articles

ALLEVIATION OF ARSENIC INDUCED THYROID DYSFUNCTION AND BODY WEIGHT ALTERATIONS BY CURCUMIN

Background: Arsenic is notorious for being used in many homicidal cases. This study was designed to observe the toxic effects of low dose of arsenic on thyroid gland and body weight and its amelioration by curcumin. Method: Thirty healthy female Sprague Dawley rats (body weight ~230 g) were procured from The National Institute of Health Islamabad. After one week of acclimatization, animals were randomly divided into three groups (n=10 each), e.g., Control group (C), Experimental group-1 (E1) and Experimental group-2 (E2). The duration of the experiment was one month. Weight of the animals was checked before and at the end of experiment. All the animals were continued on standard diet and distilled water during experimental period. E1 was given 10 µg/10 mL of arsenic by oral gavage daily. E2 was given 10 µg/10 mL of arsenic along with Curcumin (50 mg/Kg body weight/day). At the end of experiment, the rats were euthanized to draw the blood and removal of thyroid gland. Serum Triiodothyronine, Tetraiodothyronine and Thyroid Stimulating Hormone were measured by ELISA. Histological changes were observed after haematoxylin and eosin staining. Statistical analysis was done on SPSS-22 and p?0.05 was considered significant. Results: The histological findings of thyroid gland, body weight and serum T3, T4 and TSH in E1 exhibited abnormal results. E2 group showed the protecting role of curcumin suggesting protective role of curcumin. Conclusion: Curcumin has protective effects against arsenic induced thyroid disruption and body weight alterations. Pak J Physiol 2024;20(3): DOI: https://doi.org/10.69656/pjp.v20i3.1686

The regulatory role of miR-21 in ferroptosis by targeting FTH1 and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis

Arsenic is recognized as a hazardous environmental toxicant strongly associated with neurological damage, but the mechanism is ambiguous. Neuronal cell death is one of the mechanisms of arsenic-induced neurological injury. Ferroptosis is involved in the pathophysiological process of many neurological diseases, however, the role and regulatory mechanism of ferroptosis in nerve injury under arsenic exposure remains uncovered. Our findings confirmed the role of ferroptosis in arsenic-induced learning and memory disorder and revealed miR-21 played a regulatory role in neuronal ferroptosis. Further study discovered that miR-21 regulated neuronal ferroptosis by targeting at FTH1, a finding which has not been documented before. We also found an extra increase of ferroptosis in neuronal cells conditionally cultured by medium collected from arsenic-exposed microglial cells when compared with neuronal cells directly exposed to the same dose of arsenic. Moreover, microglia-derived exosomes removal or miR-21 knockdown in microglia inhibited neuronal ferroptosis, suggesting the role of intercellular communication in the promotion of neuronal ferroptosis. In summary, our findings highlighted the regulatory role of miR-21 in ferroptosis and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis.

Epicatechin as a promising agent against arsenic-induced neurobehavioral toxicity in NMRI mice: behavioral and biochemical alterations.

Epicatechin (Epi) is one of the most abundant flavonoids present in different fruits and tea leaves. Emerging research illuminates the promising potential of catechins to serve as a shield against the damaging effects of arsenic (As) exposure in diverse organs.This study sought to discern whether Epi exhibits a therapeutic efficacy against arsenic-induced neurotoxicity in a murine model.The Naval Medical Research Institute (NMRI) mice were randomly partitioned into six distinct groups, which included a control group receiving normal saline, a group receiving a daily oral dose of arsenic (10mg/kg) for 5weeks, groups receiving As (10mg/kg/day) orally for 5weeks along with different doses of Epi (25-100mg/kg) orally for the last 2weeks, and a group receiving Epi (100mg/kg) orally for 2weeks. To assess the potential effects of Epi, neurobehavioral tests, various parameters of oxidative stress, and inflammation were evaluated.The findings of this investigation revealed that As-induced neurobehavioral toxicity was associated with a notable surge in lipid peroxidation and nitric oxide (NO) concentration, accompanied by a reduction in the levels of antioxidant markers. As heightened pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) levels were observed alongside amplified nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, treatment with Epi reversed these effects.On the whole, these findings indicate that Epi may hold promise therapeutic efficacy on As-induced neurotoxicity by improving antioxidant status and mitigating oxidative stress and inflammation. Nevertheless, further research is imperative to comprehensively grasp the potential protective effects of Epi in this particular context.

The arsenic eaters of Styria, the toxicophagi

Introduction From at least the fifteenth to late nineteenth centuries, peasants in the Austrian province of Styria ate up to several hundred milligrams of arsenic trioxide or sulfide daily or weekly for periods up to a number of years. Taking these doses of arsenic was believed to increase muscular power and enhance the beauty and sexual attractiveness of peasant girls. There do not appear to be contemporaneous records of the known consequences of chronic arsenic exposure. The historical records of arsenic eating there are reviewed and appear to be valid. The benefits are subjective judgements by arsenic eaters. The lack of objective reports of the anticipated external and internal clinical and pathological effects of arsenic poisoning depends on a smaller number of clinical accounts and autopsy reports and the general medical literature of those times, so it is weaker, but it is consistent. Can the claimed benefits of arsenic eating and the apparent absence of harmful toxic effects be true? Why the arsenic eaters did not show the well-known consequences of prolonged exposure to high doses of arsenic is not known. Possible explanations include increases in detoxifying metabolism in the consumers due to induced genomic changes and selection in people and in the gut microbiome, as shown in other populations. Whether these effects would suffice to protect people against their high doses of arsenic has not been explored. Conclusion Although the nature and mechanisms of arsenic toxicity have been extensively described, much still remains to be discovered.

Reproductive and Developmental Effects of Sex-Specific Chronic Exposure to Dietary Arsenic in Zebrafish (Danio rerio).

The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), and 100 (high) μg/g dry weight, as arsenite] for 90 days. Following exposure, arsenic-exposed females from each dietary treatment were mated with control males, and similarly, arsenic-exposed males from each dietary treatment were mated with control females. In females, arsenic exposure resulted in a dose-dependent decrease in reproductive performance (fecundity, fertilization success, and hatching success). Moreover, a dose-dependent increase in developmental toxicity (larval deformities and larval mortality) was observed with maternal exposure to arsenic. In contrast, in males, arsenic exposure also induced similar reproductive and developmental toxicity; however, the adverse effects were mainly evident only in the medium and high dietary arsenic treatment groups. We also examined the sex-specific effects of dietary arsenic exposure on the expression of genes that regulate the hypothalamus-pituitary-gonadal-liver (HPG-L) axis in fish. The gene expression results indicated the downregulation of HPG-L axis genes in females irrespective of the arsenic treatment dose; however, the reduced expression of HPG-L axis genes in males was recorded only in the medium and high arsenic treatment groups. These observations suggest that chronic arsenic exposure in either females or males causes reproductive and developmental toxicity in zebrafish. However, these toxic effects are markedly higher in females than in males. Our results also suggest that arsenic can act as an endocrine disruptor and mediate reproductive and developmental toxicity by disrupting the HPG-L axis in zebrafish.

Understanding the molecular mechanism of arsenic and ammonia toxicity and high-temperature stress in Pangasianodon hypophthalmus.

The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68mg L-1, respectively) and high temperature (34°C) for 105days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34°C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122-210%, 98-122%, and 64-238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRβ; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus.

Arsenic-induced neurotoxicity in patients with acute promyelocytic leukaemia.

Arsenic trioxide is an essential component of therapy for acute promyelocytic leukaemia (APL) and is currently dosed on actual body weight with no upper limit. Arsenic-induced neurotoxicity is a well-recognised complication; however, there is uncertainty about its relationship to arsenic dose and obesity. We conducted a large multicentre retrospective study of 487 patients with APL treated with arsenic-based therapy across 23 sites in Australia from 2008 to 2023. The primary outcome was incidence of neurotoxicity, and secondary outcomes included relationship of neurotoxicity to obesity and cumulative arsenic dose. Any-grade neurotoxicity occurred in 113 (23%) patients, predominantly peripheral neuropathy (91%). Most events were grade 1-2 severity (85%), with grade 3 events in 12% and grade 4-5 in 3%. The incidence of neurotoxicity increased with BMI (non-obese: 16%, obesity class I: 25%, obesity class II-III: 41%; p < 0.001). On univariable analysis, obesity class I (OR 1.81, p = 0.036), obesity class II-III (OR 3.93, p < 0.001), weight >100 kg (OR 2.72, p < 0.001), daily arsenic trioxide dose >15 mg (OR 5.05, p < 0.001) and cumulative induction dose >500 mg (OR 3.95, p < 0.001) were all significantly associated with neurotoxicity. Obesity class II-III and induction dose >500 mg remained significant on multivariable analysis. Our study highlights the strong association between BMI, arsenic trioxide dose and neurotoxicity. Pre-emptive dose reductions should be considered for obese patients receiving high doses of arsenic.

Biomarkers of arsenic exposure in biogeochemical provinces

Introduction. One of the direct methods of assessing the impact of contaminants on public health is the use of biological markers that allow determining the presence of a substance or its metabolite in human biological tissues and the dose received from all sources of this substance. &#x0D; The purpose of this study was to determine the dependence of arsenic content in biological samples (hair) &#x0D; of exposed residents on the level of its content in drinking water and to substantiate the effectiveness of the use of this biomarker in the conditions of a hydrogeochemical province in the Republic of Dagestan.&#x0D; Material and methods. During this research the arsenic content in the hair of the exposed residents was measured with further comparison of the data obtained with its content in drinking groundwater. To determine the arsenic content in the hair of the exposed residents, an atomic absorption method was used with preliminary preparation of biosubstrate samples. Socio-demographic data were obtained from a questionnaire. Statistical data processing was carried out using Microsoft Excel.&#x0D; Results. In the course of this study, a correlation was revealed between the arsenic content in the hair of the exposed residents and its content in the drinking water consumed, and a direct proportional relationship between these values was also revealed. Thus, with an increase in the concentration of arsenic in water by &#x0D; 0.1 mg/l, the arsenic content in the hair increases by 0.14 mkg/g. So, using of the hair of exposed residents as a biomarker of long-term exposure is recommended to small doses of arsenic in a biogeochemical province.&#x0D; limitation of the study is the small sample size. However, this does not prevent the assessment of the effectiveness of using hair as a biomarker of arsenic exposure and preliminary conclusions for subsequent in-depth analysis of biomonitoring in the conditions of biogeochemical provinces.&#x0D; Conclusion. As a rule, the content of natural toxic elements is characterized by trace amounts in the conditions of biogeochemical provinces. Biomonitoring will reveal the level of stress on the body and timely apply preventive methods before the clinical signs of intoxication are revealed.

P53-Mediated Mitochondrial Translocation of EI24 Triggered by ER Stress Plays an Important Role in Arsenic-Induced Liver Damage via Activating Mitochondrial Apoptotic Pathway.

Chronic arsenic poisoning is a public health problem worldwide. In addition to skin lesions, the detrimental effect of arsenic poisoning on liver damage is one of the major issues. Our previous studies demonstrated that endoplasmic reticulum (ER) stress and p53 were associated with arsenic-induced liver damage. Literature has shown that EI24 is involved in hepatocyte hypertrophy; however, the underlying role and mechanism in arsenic-induced liver damage have not been fully elucidated. In this study, we explored the role of ER stress, p53, and EI24 as well as the regulatory relationship in arsenic poisoning populations and L-02 cells treated with distinct concentration NaAsO2 (2.5, 5, 10, and 20μM). Results showed that as with arsenic dose increment, expression levels of ER stress key proteins GRP78, ATF4, and CHOP were significantly enhanced. Additionally, p53 expression in nucleus, p53 phosphorylation at Ser15 and Ser1392, and p53 acetylation at lys382 were significantly increased in NaAsO2-treated L-02 cells. ER stress inhibitor 4-phenylbutyric acid (4-PBA) decreased the expression of p53 phosphorylation at Ser 392, p53 acetylation at lys382, and p53 expression in nucleus. Additionally, in 5μM NaAsO2 condition, p53 inhibitor pifithrin-α (PFT-α) aggravated 5μM NaAsO2-induced GRP78, ATF4, and CHOP expressions, cell apoptosis, and protein-SH consumption. But in 20μM NaAsO2 condition, PFT-α attenuated NaAsO2-induced cell apoptosis. Further results showed that 20μM NaAsO2 facilitated translocation of EI24 from ER to mitochondrion and interaction with VDAC2, leading to activate mitochondrial apoptotic pathway, but not observed in the 5-μM NaAsO2 group. Moreover, PFT-α and 4-PBA inhibited 20μM NaAsO2-induced EI24 expression in mitochondrion. Collectively, our results indicated that arsenic induced p53 activation via ER stress, under relatively low NaAsO2 concentration, NaAsO2-triggered p53 activation protected cells from apoptosis by alleviating ER stress. Another finding was that under relatively high NaAsO2 concentration, NaAsO2-activated p53 facilitated EI24 mitochondrial translocation and caused mitochondrial permeability increase, which represented a switch of p53 from a benefit role to pro-apoptosis function in NaAsO2-treated cells. The study contributed to in-depth understanding the mechanism of arsenic-induced liver damage and providing potential clues for following study.

The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice.

Both excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or because of arsenic found directly in alcoholic beverages. This study aims to determine if co-exposure to alcohol and arsenic leads to worse outcomes in neurodegeneration and associated mechanisms that could lead to cell death. To study this, mice were exposed to a 10-day gavage model of alcohol-induced neurodegeneration with varying doses of arsenic (0, 0.005, 2.5, or 10 mg/kg). The following were examined after the last dose of ethanol: (1) microglia activation assessed via immunohistochemical detection of Iba-1, (2) reactive oxygen and nitrogen species (ROS/RNS) using a colorimetric assay, (3) neurodegeneration using Fluoro-Jade® C staining (FJC), and 4) arsenic absorption using ICP-MS. After exposure, there was an additive effect of the highest dose of arsenic (10 mg/kg) in the dentate gyrus of alcohol-induced FJC+ cells. This additional cell loss may have been due to the observed increase in microglial reactivity or increased arsenic absorption following co-exposure to ethanol and arsenic. The data also showed that arsenic caused an increase in CYP2E1 expression and ROS/RNS production in the hippocampus which could have independently contributed to increased neurodegeneration. Altogether, these findings suggest a potential cyclical impact of co-exposure to arsenic and ethanol as ethanol increases arsenic absorption but arsenic also enhances alcohol's deleterious effects in the CNS.

Testicular Toxicity following Subacute Exposure of Arsenic and Mancozeb alone and in Combination: Ameliorative Efficacy of Quercetin and Catechin

Mancozeb (MZ) is a contact fungicide having low toxicity in non-target species, but its continuous exposure can be harmful. The aim of the present study was to determine the impact of the toxic interaction between MZ and arsenic on the testicular tissue of rats and to compare the amelioration potential of quercetin and catechin against the induced toxicity. Sixty adult rats were randomly allocated into 10 groups with 6 animals in each. A significant (p&lt;0.05) decline in TAS, TTH, SOD, CAT, GPx, GR and TTH and a rise (p&lt;0.05) in MDA and AOPP-were recorded in testicular tissue of MZ-treated rats in comparison to control. Exposure to different doses of arsenic (10, 50, 100 ppb) also produced a dose-dependent effect on these oxidative biomarkers. Arsenic exposure produces potentiating MZ-induced testicular toxicity in Wistar rats. Testicular damage was further corroborated by extremely severe histopathological changes viz., interstitial as well as sub-capsular congestion, oedema aside from degeneration, necrosis and loss of seminiferous tubules and a drastic deterioration in sperm motility in this group. In contrast, administration of toxicants along with quercetin or catechin markedly attenuated the alterations in oxidative as well as cellular damage biomarkers and testicular histopathological alterations. Our results suggested that simultaneous low dose exposure to arsenic potentiated testicular toxicity induced by MZ. Furthermore, catechin was more potent as compared to quercetin in ameliorating testicular changes induced by concurrent arsenic and MZ exposure.

Occupational arsenic exposure and genitourinary cancer: systematic review and meta-analysis.

Existing evidence suggests that ingestion of high doses of arsenic through drinking water is associated with an increased risk of genitourinary cancers, while systematic evidence on workers exposed to arsenic is lacking. The aim of this study is to systematically review the evidence on the association between occupational exposure to arsenic and genitourinary cancer risk and mortality. A systematic literature search was carried out on Pubmed, Web of Science and Embase by including cohort and case-control studies. Study-specific relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using Mandel-Paule random-effects model. Contour-enhanced funnel plot and Egger's test were used to assess the occurrence of publication bias. A total of 17 studies were included in the meta-analysis, 7 on cancer incidence (n = 161,244 individuals) and 10 on cancer mortality (n = 91,868). Most of them were cohort (71%) and industry-based studies (59%). The meta-analysis failed to detect an increased risk of genitourinary cancers among workers exposed to arsenic, except for a suggestive but not significant positive association for bladder cancer incidence (RR: 1.26, 95% CI: 0.89, 1.80), although this estimate was based on only three studies. No compelling evidence of publication bias was found (P = 0.885). Our findings did not show an association between occupational exposure to arsenic and genitourinary cancers, although further high-quality studies with detailed exposure assessment at the individual level are needed to clarify this relationship.

SIRT1/P53 pathway is involved in the Arsenic induced aerobic glycolysis in hepatocytes L-02 cells.

Arsenic is a known human carcinogen. Low doses of arsenic can induce cell proliferation, but the mechanism remains elusive. Aerobic glycolysis, also known as the Warburg effect, is one of the characteristics of tumour cells and rapidly proliferating cells. P53 is a tumour suppressor gene that has been shown to be a negative regulator of aerobic glycolysis. SIRT1 is a deacetylase that inhibits the function of P53. In this study, we found that P53 was involved in low dose of arsenic-induced aerobic glycolysis through regulating HK2 expression in L-02 cells. Moreover, SIRT1 not only inhibited P53 expression but also decreased the acetylation level of P53-K382 in arsenic-treated L-02 cells. Meanwhile, SIRT1 influenced the expression of HK2 and LDHA, which then promoted arsenic-induced glycolysis in L-02 cells. Therefore, our study demonstrated that the SIRT1/P53 pathway is involved in arsenic-induced glycolysis, thereby promoting cell proliferation, which provides theoretical basis for enriching the mechanism of arsenic carcinogenesis.

Chronic dietary exposure to arsenic at environmentally relevant concentrations impairs cognitive performance in adult zebrafish (Danio rerio) via oxidative stress and dopaminergic dysfunction

The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 μg/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 μg/g dw) and high (100 μg/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2_mg, entpd2_mq, and 5′-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxidative stress and disrupting the dopaminergic neurotransmission in the brain.

Cross-sectional associations between drinking water arsenic and urinary inorganic arsenic in the United States: NHANES 2003–2014

BackgroundInorganic arsenic is a potent carcinogen and toxicant associated with numerous adverse health outcomes. The contribution of drinking water from private wells and regulated community water systems (CWSs) to total inorganic arsenic exposure is not clear. ObjectivesTo determine the association between drinking water arsenic estimates and urinary arsenic concentrations in the 2003–2014 National Health and Nutrition Examination Survey (NHANES). MethodsWe evaluated 11,088 participants from the 2003–2014 NHANES cycles. For each participant, we assigned private well and CWS arsenic levels according to county of residence using estimates previously derived by the U.S. Environmental Protection Agency and U.S. Geological Survey. We used recalibrated urinary dimethylarsinate (rDMA) to reflect the internal dose of estimated water arsenic by applying a previously validated, residual-based method that removes the contribution of dietary arsenic sources. We compared the adjusted geometric mean ratios and corresponding percent change of urinary rDMA across tertiles of private well and CWS arsenic levels, with the lowest tertile as the reference. Comparisons were made overall and stratified by census region and race/ethnicity. ResultsOverall, the geometric mean of urinary rDMA was 2.52 (2.30, 2.77) μg/L among private well users and 2.64 (2.57, 2.72) μg/L among CWS users. Urinary rDMA was highest among participants in the West and South, and among Mexican American, Other Hispanic, and Non-Hispanic Other participants. Urinary rDMA levels were 25% (95% confidence interval (CI): 17–34%) and 20% (95% CI: 12–29%) higher comparing the highest to the lowest tertile of CWS and private well arsenic, respectively. The strongest associations between water arsenic and urinary rDMA were observed among participants in the South, West, and among Mexican American and Non-Hispanic White and Black participants. DiscussionBoth private wells and regulated CWSs are associated with inorganic arsenic internal dose as reflected in urine in the general U.S. population.

Sodium Arsenite in Drinking Water is a Continuous Threat to Maturing Reproductive System: a Study in Prepubertal Male Mice

Human exposure to arsenic in countries known for heavy arsenic load, where ground water arsenic level exceeds the WHO limit, can be detrimental for developing gonads. Developmental and reproductive toxicity of arsenic in rodents after in utero exposure is although known but information on the toxic effects of arsenic on postnatal gonadal development is scant. This aspect was the focus of the present investigation. Postnatal day 25 prepubertal male mice were challenged with sub-chronic and chronic (up to PND 53 & PND 114 respectively) oral exposure (drinking water) to low and high doses (0.01, 5, and 10 mg.L-1) of sodium arsenite. Data were compared statistically at P<0.05. Sub-chronic exposure to high arsenic doses led to significant increase in the production of reactive oxygen species and lipid peroxidation, while simultaneous significant reduction occurred in the activity of antioxidant enzymes catalase, superoxide dismutase and peroxidase, hormone concentrations (folliclestimulating hormone, luteinizing hormone, testosterone) and sperm parameters. Testicular cell damage and sperm DNA damage, as revealed by comet assay, were evident at 10 mg.L-1arsenic dose. Chronic exposure further aggravated the adverse effects. Severe testicular oxidative stress, reduction in hormones and pronounced histological alterations in testis and epididymis, and sperm parameters together with excessive sperm DNA damage were noticeable even at the lowest test dose of 0.01 mg.L-1. The study concludes that arsenic exposure considerably affects the prepubertal gonad, may cause irreversible damage to the developing reproductive system of males and that minute quantity of arsenic in drinking water can be a serious health hazard.

Arsenic-induced differential inflammatory responses in mouse thymus involves NF-κB/STAT-3 disruption, Treg bias and autophagy activation

AimArsenic contamination in drinking water is a world-wide public health concern. Sustained arsenic ingestion leads to immune alterations and subsequent development of inflammatory and autoimmune diseases; however, the underlying cellular and molecular intricacies of immunotoxicity remains uncharacterized. We aim to understand how exposure to arsenic at different concentrations affects the immune system differentially and whether arsenic-induced differential inflammation dictates altered T-regulatory cell bias and emphasize the role of autophagy in the pathway. Main methodsSwiss albino mice were exposed to environmentally relevant concentrations of arsenic in drinking water for 28 days. Examination of thymic cyto-architecture was done to evaluate thymic damage. ELISA was performed for key cytokines. Flow cytometry, western blotting, and immunostaining were performed for cell surface and intracellular proteins. Co-immunoprecipitation and transfection with siRNA were performed to examine the direct physical interactions between proteins. Key findingsOur study distinctly demonstrates that arsenic-induced oxidative stress instigates NF-κB activation, which not only provokes pro-inflammatory responses, but also exhibits immune-suppressive activity depending on the dose of arsenic. Co-immunoprecipitation of NF-κBp65 and pSTAT-3 reveals that arsenic alters their physical interaction, thereby suppressing IL-6/STAT-3/IL-17A feedback loop. Flow cytometry and silencing studies demonstrate that NF-κB-driven Treg cell differentiation induces immune-suppression through FoxP3 up-regulation at the highest dose of arsenic and such immune-suppression is actively supported by NF-κB-driven autophagy activation. SignificanceCollectively, our findings reveal that exposure to arsenic differentially impacts the immune system and understanding the molecular cascade might provide direction for prevention/treatment of arsenic-induced inflammatory and autoimmune diseases.

Assessment of the Hormetic Effect of Arsenic on Growth and Physiology of Two Cultivars of Maize (Zea mays L.).

Although growth stimulation at low arsenic doses was observed in several plants, few studies have focused on this phenomenon in more detail. The effects of different concentrations of arsenic (0-50 mg kg-1 of soil: As0-As50) on the growth and selected physiological parameters of two maize cultivars (Zea mays L. cvs. Chapalu and MvNK 333) were tested. Cultivar MvNK 333 manifested a generally higher tolerance to As than cv. Chapalu, which may be related to the lower content of As in the tissues. The highest stimulatory effect of As was recorded at doses of As1 and As2 (cv. Chapalu), and at the As5 dose (MvNK 333), there was an increase in shoot elongation, biomass, and relative water content (RWC), as well as the content of photosynthetic pigments. The stimulatory effect of lower doses of As apparently represents an adaptation mechanism that is associated with water content regulation in the given conditions. The stomata of the studied cultivars were involved in this regulation in different ways. While cv. Chapalu exhibited increased numbers of stomata on both sides of leaves, cv. MvNK 333 instead responded to the given conditions with decreased stomata size. Although hormetic manifestations closely related to changes in stomatal number and size were observed, a typical stomatal hormetic response was not observed in the given range of As doses.

The ROS/NF-κB/HK2 axis is involved in the arsenic-induced Warburg effect in human L-02 hepatocytes

ABSTRACT Arsenic has been identified as a carcinogen, although the molecular mechanism underlying itscarcinogenesis has not been fully elucidated. To date, only a few studies have attempted to confirm a direct link between oxidative stress and the Warburg effect . This study demonstrated that 0.2 μmol/L As3+ induced the Warburg effect to contribute to abnormal proliferation of L-02 cells, that was mediated by upregulation of hexokinase 2 (HK2), a key enzyme in glycolysis. Further study indicated that arsenic-induced accumulation of reactive oxygen species (ROS) activated the nuclear factor kappa B (NF-κB) signaling pathway by phosphorylation of p65 at the Ser536 and Ser276 sites, leading to upregulated expression of HK2. We therefore concluded that the ROS/NF-κB/HK2 axis contributes to the Warburg effect and cell proliferation induced by low doses of arsenic. AbbreviationsROS, Reactive oxygen species; NAC, N-acetyl-L-cysteine; 2-DG, 2-deoxy-D-glucose; 2-NBDG, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose

Effective removal of arsenic (V) from aqueous solutions using efficient CuO/TiO2 nanocomposite adsorbent

The groundwater is one of the biggest natural resources for providing drinking water to millions of people all around the globe. However, the presence of large amount of arsenic(V) in water causes serious health hazards to the consumers which necessitates the development of cost-effective remediation. The CuO/TiO2 nanocomposites were prepared by the precipitation-deposition method for the removal of the arsenate ion (AsO43-) from water. The prepared samples were characterized by powder X-ray diffraction, Fourier transform infrared, and scanning electron microscopy to examine crystallite size and structure, material purity, textural features, morphology, and surface area. The effect of different operating parameters such as pH, contact time, initial concentration of arsenic(V) and nanocomposite dose on the removal rate of arsenic(V) was examined to optimize the adsorption performance of the CuO/TiO2 nanocomposite. In addition, the adsorption mechanism was studied by employing Langmuir and Freundlich adsorption isotherms to gain better understanding of the adsorption mechanism. The Freundlich adsorption isotherm fits well with the experimental data and the maximum adsorption capacity of the Langmuir model was found to be 90 mg/g for arsenic(V). The CuO/TiO2 nanocomposite shows remarkable adsorption performance for the treatment of arsenic(V) contaminated water samples. This study provides a cost-effective solution for the safe use of groundwater contaminated with arsenic.