Non-Uniform Bioaccumulation of Lead and Arsenic in Two Remote Regions of the Human Heart's Left Ventricle: A Post-Mortem Study.

The extent of heavy-metal-induced cardiotoxicity is proportional to the levels of metal bioaccumulation, and it was previously assumed that heavy metals accumulate uniformly in the myocardium. Therefore, the aim of this study was to investigate concentrations of metals and metalloids in two distant regions of the left ventricle (LV), the base of the LV, and apex of the LV using inductively coupled plasma mass spectrometry (ICP-MS). We also examined the potential correlation between metal levels and the thickness of the interventricular septum in twenty LV specimens (ten from the base of LV and ten from the apex of LV) from 10 individuals (mean age 75 ± 6 years). We found significantly higher concentrations of arsenic and lead in the LV apex compared to the base of the LV. We also found a positive correlation between the concentrations of arsenic in the myocardium of LV and the thickness of the interventricular septum. Our results indicate that arsenic and lead accumulate to a higher extent in the apex of the LV compared to the base of the LV. Therefore, future studies designed to measure levels of metals in heart muscle should consider non-uniform accumulation of metals in the myocardium.

Evaluating the mouse model for estimation of arsenic bioavailability: Comparison of estimates of absolute bioavailability of inorganic arsenic in mouse, humans, and other species.

Accurate assessment of adverse health effects attributable to ingestion of inorganic arsenic (As) present in contaminated soils requires determination of the internal dose of metal provided by ingested soil. This calculation requires estimation of the oral bioavailability of soil-borne (As). Animal models to assess the bioavailability of soil (As) are frequently used as surrogates for determination of this variable in humans. A mouse assay has been widely applied to estimate the bioavailability of As in soils at sites impacted by mining, smelting, and pesticides. In the mouse assay, the relative bioavailability (RBA) of soil (As) is determined as the ratio of the fraction of the ingested arsenic dose excreted in urine after consumption of diets containing a test soil or the soluble reference compound, sodium arsenate. The aim of the current study was to compare (As) bioavailability measured in the mouse assay with reported estimates in humans. Here, a pharmacokinetic model based on excretion of arsenic in urine and feces was used to estimate the absolute bioavailability (ABA) of As in mice that received an oral dose of sodium arsenate. Based upon this analysis, in mice that consumed diet amended with sodium arsenate, the ABA was 85%. This estimate of arsenic ABA for the mouse is comparable to estimates in humans who consumed (As) in drinking water and diet, and to estimates of ABA in monkeys and swine exposed to sodium arsenate. The concordance of estimates for ABA in mice and humans provides further support for use of the mouse model in human health risk assessment. Sodium arsenate ABA also provides a basis for estimating soil arsenic ABA from RBA estimates obtained in the mouse model.

Bioavailability and health risk of toxic heavy metals (As, Hg, Pb and Cd) in urban soils: A Monte Carlo simulation approach.

Toxic heavy metals pollution in urban soil has become a major global issue due to its adverse effects on the environment and human health. In this paper, 26 soil samples were analyzed to assess the speciation, bioavailability and human health risk of Arsenic (As), Mercury (Hg), Lead (Pb) and Cadmium (Cd) in urban soils of a heavy industrial city in NE China by using a Monte Carlo simulation approach. The results showed that As, Hg, Pb and Cd concentrations in the soil all exceed the corresponding background value of study area. Mercury displays the highest value of geo-accumulation index (Igeo), followed by Cd, Pb and As. The pollution load index (PLI) value (>2) indicates a moderate pollution level in the study area. The chemical speciation of HMs mainly exists in residual fraction except Cd. The probabilistic health risk assessment demonstrated that the mean values of Total Carcinogenic Risk (TCR) and Hazard Index (HI) calculated with total concentration are at the unacceptable level, with a higher risk to children than adults. However, the mean values calculated with bioavailable fraction are all within the acceptable level. The mean value of TCR and HI obtained by bioavailable fraction is about 96% and 95% lower than that obtained by total concentration, respectively. Thus, this study suggested that the bioavailable fraction of HMs is a more reliable parameter for health risk assessment, while the total concentration of HMs can overestimate the true risk. The results of this study provide some insight into the speciation, bioavailability and health risks of toxic heavy metals in urban soils in those heavy industrial cities.

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression.

BACKGROUND: Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. RESULTS: Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. CONCLUSIONS: This work provides a new paradigm for the treatment of residual HCC after IRFA.

Interconnected soil iron and arsenic speciation effects on arsenic bioaccessibility and bioavailability: a scoping review.

Extensive research has examined arsenic (As) bioavailability in contaminated soils and is routinely assessed using in vitro bioaccessibility (IVBA) assays. Analysis of differences in bioaccessibility measurements across IVBA assays and phases is expected to provide valuable insights into geochemical mechanisms controlling soil As bioaccessibility and bioavailability. Soil iron (Fe) content and As speciation are expected to significantly influence IVBA gastric and intestinal phases due to fluctuations in precipitation-dissolution chemistry and sorption reactivity as pH and assay chemical complexity changes. The aim of this review was to examine these relationships by 1) conducting a meta-analysis (n = 47 soils) determining the influence of total Fe on As bioaccessibility measurements and 5 IVBA assays and 2) investigating the effect of As speciation on gastric/intestinal phase IVBA and in vitro-in vivo correlations. Our findings indicate that soil Fe content and As speciation heterogeneity are important in elucidating variability of bioaccessibility measurements across IVBA assays and gastrointestinal phases. Greater focus on coupled As speciation and Fe precipitation chemistry may (1) improve our understanding of soil geochemical factors and assay constituents that influence As in vitro-in vivo correlations and (2) resolve variability in the precision of oral relative bioavailability (RBA) estimated using IVBA assays for soils possessing heterogenous As speciation and Fe composition.

Bioavailability of arsenic, cadmium, lead and mercury as measured by intestinal permeability.

In this study, the intestinal permeability of metal(loid)s (MLs) such as arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) was examined, as influenced by gut microbes and chelating agents using an in vitro gastrointestinal/Caco-2 cell intestinal epithelium model. The results showed that in the presence of gut microbes or chelating agents, there was a significant decrease in the permeability of MLs (As-7.5%, Cd-6.3%, Pb-7.9% and Hg-8.2%) as measured by apparent permeability coefficient value (Papp), with differences in ML retention and complexation amongst the chelants and the gut microbes. The decrease in ML permeability varied amongst the MLs. Chelating agents reduce intestinal absorption of MLs by forming complexes thereby making them less permeable. In the case of gut bacteria, the decrease in the intestinal permeability of MLs may be associated to a direct protection of the intestinal barrier against the MLs or indirect intestinal ML sequestration by the gut bacteria through adsorption on bacterial surface. Thus, both gut microbes and chelating agents can be used to decrease the intestinal permeability of MLs, thereby mitigating their toxicity.

Mendelian randomization analysis of arsenic metabolism and pulmonary function within the Hispanic Community Health Study/Study of Latinos.

Arsenic exposure has been linked to poor pulmonary function, and inefficient arsenic metabolizers may be at increased risk. Dietary rice has recently been identified as a possible substantial route of exposure to arsenic, and it remains unknown whether it can provide a sufficient level of exposure to affect pulmonary function in inefficient metabolizers. Within 12,609 participants of HCHS/SOL, asthma diagnoses and spirometry-based measures of pulmonary function were assessed, and rice consumption was inferred from grain intake via a food frequency questionnaire. After stratifying by smoking history, the relationship between arsenic metabolism efficiency [percentages of inorganic arsenic (%iAs), monomethylarsenate (%MMA), and dimethylarsinate (%DMA) species in urine] and the measures of pulmonary function were estimated in a two-sample Mendelian randomization approach (genotype information from an Illumina HumanOmni2.5-8v1-1 array), focusing on participants with high inferred rice consumption. Among never-smoking high inferred consumers of rice (n = 1395), inefficient metabolism was associated with past asthma diagnosis and forced vital capacity below the lower limit of normal (LLN) (OR 1.40, p = 0.0212 and OR 1.42, p = 0.0072, respectively, for each percentage-point increase in %iAs; OR 1.26, p = 0.0240 and OR 1.24, p = 0.0193 for %MMA; OR 0.87, p = 0.0209 and OR 0.87, p = 0.0123 for the marker of efficient metabolism, %DMA). Among ever-smoking high inferred consumers of rice (n = 1127), inefficient metabolism was associated with peak expiratory flow below LLN (OR 1.54, p = 0.0108/percentage-point increase in %iAs, OR 1.37, p = 0.0097 for %MMA, and OR 0.83, p = 0.0093 for %DMA). Less efficient arsenic metabolism was associated with indicators of pulmonary dysfunction among those with high inferred rice consumption, suggesting that reductions in dietary arsenic could improve respiratory health.

Arsenic toxicokinetic modeling and risk analysis: Progress, needs and applications.

Arsenic (As) poses unique challenges in PBTK model development and risk analysis applications. Arsenic metabolism is complex, adequate information to attribute specific metabolites to particular adverse effects in humans is sparse, and measurement of relevant metabolites in biological media can be difficult. Multiple As PBTK models have been published and used or adapted for use in various exposure and risk analysis applications. These applications illustrate the broad utility of PBTK models for exposure and dose-response analysis, particularly for arsenic where multi-pathway, multi-route exposures and multiple toxic effects are of concern. Arsenic PBTK models have been used together with exposure reconstruction and dose-response functions to estimate risk of specific adverse health effects due to drinking water exposure and consumption of specific foodstuffs (e.g. rice, seafood), as well as to derive safe exposure levels and develop consumption advisories. Future refinements to arsenic PBTK models can enhance the confidence in such analyses. Improved estimates for methylation biotransformation parameters based on in vitro to in vivo extrapolation (IVIVE) methods and estimation of interindividual variability in key model parameters for specific toxicologically relevant metabolites are two important areas for consideration.

An interlaboratory evaluation of the variability in arsenic and lead relative bioavailability when assessed using a mouse bioassay.

Animal bioassays have been developed to estimate oral relative bioavailability (RBA) of metals in soil, dust, or food for accurate health risk assessment. However, the comparability in RBA estimates from different labs remains largely unclear. Using 12 soil and soil-like standard reference materials (SRMs), this study investigated variability in lead (Pb) and arsenic (As) RBA estimates employing a mouse bioassay in 3 labs at Nanjing University, University of Jinan, and Shandong Normal University. Two performances of the bioassay at Nanjing University in 2019 and 2020 showed reproducible Pb and As RBA estimates, but increasing the number of mouse replicates in 2020 produced more precise RBA measurements. Although there were inter-lab variations in diet consumption rate and metal accumulation in mouse liver and kidneys following SRM ingestion due to differences in diet composition, bioassays at 3 labs in 2019 yielded overall similar Pb and As RBA estimates for the 12 SRMs with strong linear correlations between each 2 of the 3 labs for Pb (R2 = 0.95-0.98 and slope = 0.85-1.02) and As RBA outcomes (R2 = 0.46-0.86 and slope = 0.56-0.79). The consistency in RBA estimates was attributed to the relative nature of the final bioavailability outcome, which might overcome the inter-lab variation in diet consumption and metal uptake in mice. These results increased the confidence of use of mouse bioassays in bioavailability studies.

Exogenous melatonin regulates endogenous phytohormone homeostasis and thiol-mediated detoxification in two indica rice cultivars under arsenic stress.

KEY MESSAGE: Melatonin enhanced arsenic (As) tolerance by inhibiting As bioaccumulation, modulating the expression of As transporters and phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid. The present study was aimed at investigating the influence of exogenous melatonin on the regulation of endogenous plant growth regulators and their cumulative effects on metal(loid)-binding ligands in two contrasting indica rice cultivars, viz., Khitish (arsenic sensitive) and Muktashri (arsenic tolerant) under arsenic stress. Melatonin supplementation ameliorated arsenic-induced perturbations by triggering endogenous levels of gibberellic acid and melatonin, via up-regulating the expression of key biosynthetic genes like GA3ox, TDC, SNAT and ASMT. The endogenous abscisic acid content was also enhanced upon melatonin treatment by induced expression of the key anabolic gene, NCED3 and concomitant suppression of ABA8ox1. Enhanced melatonin content induced accumulation of higher polyamines (spermidine and spermine), together with up-regulation of SPDS and SPMS in Khitish, thereby modulating stress condition. On the contrary, melatonin escalated putrescine and spermidine levels in Muktashri, via enhanced expression of ADC and SAMDC. The role of melatonin appeared to be more prominent in Khitish, as evident from better utilization of thiol components like cysteine, GSH, non-protein thiols and phytochelatins, with higher GSH/GSSG ratio, despite down-regulated expression of corresponding thiol-metabolic genes (OsMT2 and OsPCS1) to deal with arsenic toxicity. The extent of arsenic bioaccumulation, which was magnified several folds, particularly in Khitish, was decreased upon melatonin application. Overall, our observation highlighted the fact that melatonin enhanced arsenic tolerance by inhibiting arsenic bioaccumulation, via modulating the expression levels of selected arsenic transporters (OsNramp1, OsPT2, OsPT8, OsLsi1) and controlling endogenous phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid.

Population Pharmacokinetics and Safety of Oral Tetra-Arsenic Tetra-Sulfide Formula in Pediatric Acute Promyelocytic Leukemia.

BACKGROUND: An oral tetra-arsenic tetra-sulfide (AS4S4) formula has been recommended as an outpatient post-remission treatment for Chinese adults with acute promyelocytic leukemia (APL) but limited data are available for children. In this exploratory study, we aimed to evaluate the pharmacokinetics and safety of the AS4S4 formula in children. METHODS: Eleven newly diagnosed and one relapsed pediatric patient (4-14 years of age) treated with the AS4S4 formula were included. Blood samples were collected from 12 children, and drug concentrations were quantified by ICP-MS. Population pharmacokinetic analysis and Monte-Carlo simulation were performed using NONMEM software. Toxic effects were graded according to the NCI-CTCAE, Version 3. RESULTS: A total of 107 arsenic concentrations (0.1-75.0 µg L-1) were used for population pharmacokinetic analysis. The median (range) of estimated weight-normalized CL and volume distribution at steady-state were 45.26 (35.63-82.18) L h-1 kg-1 and 230.37 (85.96-495.68) L kg-1, respectively. No patients discontinued AS4S4 treatment owing to adverse events, and there were no drug-related adverse events over grades 3-4. All newly diagnosed APL patients were in MCR with a median follow-up of 28 months (range, 23 to 37 months). Both the estimated 3-year EFS and OS rates were 100%. CONCLUSION: The pharmacokinetics and safety oral AS4S4 formula was evaluated for the first time in pediatric APL. The pharmacokinetic assessment demonstrated that the dosing regimen of 60 mg/kg/d TID resulted in a higher steady-state through concentration in children than that which was achieved in adults. The results of this study indicate that the AS4S4 formula is safe in newly diagnosed pediatric APL patients.

Contrasted tolerance of Agrostis capillaris metallicolous and non-metallicolous ecotypes in the context of a mining technosol amended by biochar, compost and iron sulfate.

Metal(loid) contamination of soil, resulting from the mining activities, is a major issue worldwide, due to its negative effects on the environment and health. Therefore, these contaminated soils need to be remediated. One realistic method is the assisted phytostabilization, which aims at establishing a vegetation cover on the soil that will reduce metal(loid) bioavailability and spreading through the prevention of wind erosion and water leaching. In addition, amendments are applied to improve soil conditions and ameliorate plant growth. In this goal, biochar and compost showed good results in terms of amelioration of soil fertility and reduction in lead bioavailability. However, they usually have a negative effect on arsenic. On the contrary, iron sulfate showed capacity to reduce arsenic mobility through interaction with its iron hydroxides. Finally, the choice of the appropriate plant species is crucial for the success of assisted phytostabilization. One good option is to use endemic species, adapted to the metal(loid) stress, with a fast growth and large shoot and root systems. The aims of this study were to (1) evaluate the effects of applying biochar, compost and iron sulfate, alone or combined, to a former mine soil on the soil properties and Agrostis capillaris growth, and (2) assess the difference between two Agrostis capillaris ecotypes, an endemic metallicolous ecotype and a non-metallicolous ecotype. Results of the mesocosm experiment showed that amendment application improved soil properties, i.e., reduced soil acidity, increased nutrient availability and lower metal(loid) stress, the best being the combination biochar-compost-iron sulfate. These ameliorations allowed a better plant growth. Finally, the metallicolous ecotype performed better in terms of growth than the non-metallicolous one and could thus be used in an assisted phytostabilization process on the former mine site.

Differential distribution of and similar biochemical responses to different species of arsenic and antimony in Vetiveria zizanioides.

Vetiver grass (Vetiveria zizanioides L. Nash) has a great application potential to the phytoremediation of heavy metals pollution. However, few studies explored the bioavailability and distribution of different speciations of As and Sb in V. zizanioides. This study aimed to clarify the allocation and accumulation of two inorganic species arsenic (As(III) and As(V)) and antimony (Sb(III) and Sb(V)) in V. zizanioides, to understand the self-defense mechanisms of V. zizanioides to these metal(loids) elements. Thus, an experiment was conducted under greenhouse conditions to identify distribution of As and Sb in plant roots and shoots. Antioxidant enzymes (superoxide dismutase, SOD) and changes of subcellular structures were tested to evaluate metal(loids) tolerance capacities of V. zizanioides. This study demonstrated that V. zizanioides had higher capacity to accumulate Sb than As. For Sb absorption, Sb(III) content is significantly higher than Sb(V) in tissues of V. zizanioides under all concentration levels, despite the oxidation of Sb(III) on the nutrient solution surface. Additional Sb was mainly accumulated in plant roots due to Sb immobilization by transforming it into precipitates. As was more easily transferred to aerial tissues and had low accumulation rates, probably due to its restricted uptake rather than restricted transport. In many cases, two inorganic species of As and Sb showed almost same biotoxicity to V. zizanioides estimated from its biomass, SOD activity, and MDA content as well as functional groups. In summary, the results of this study provide new insights into understanding allocation, accumulation and phytotoxicity effects of arsenic and antimony in V. zizanioides. Schematic diagram of distribution of and biochemical responses to As(III), As(V), Sb(III), and Sb(V) in tissue of V. zizanioides.

Arsenic in the rock-soil-plant system and related health risk in a magmatic-metamorphic belt, West of Iran.

Following earlier reports of water contamination and arsenic (As) toxicity symptoms in residents of Kurdistan Province, As was determined in rock, soil and plant samples to investigate its fate from rock to crops and its potential effects on human health. Total As content ranged from 4.9 to 10,000 mg/kg, 7.7-430 mg/kg and < 0.05-25,079 µg/kg (dry weight) in rock, soil and plant samples, respectively. The Qorveh-Bijar region data indicated that magmatic differentiation has enriched late magmatic fluids in As. High rare earth elements concentration, dissociation coefficient, and positive Eu anomaly in volcanic rocks, indicated the prevalence of intermediate to felsic composition. The highest As concentration was measured in travertine. In soil, As average level in Qorveh and Bijar was 48.5 and 107 mg/kg, respectively. Higher pollution index and geoaccumulation index (Igeo) were also calculated for Bijar County. The As concentration in crop samples was greater than the recommended maximum permissible concentration for foodstuff. Mann-Whitney U test revealed significant differences between As concentration in different plant species and no difference between plants in Bijar and Qorveh. Also, alfalfa displayed the highest biological accumulation coefficient among the investigated plants. The calculated chronic daily intake of As in Bijar County was higher than the recommended levels for wheat and barley grains. Moreover, the hazard quotient (HQ) and incremental lifetime cancer risk assessments revealed high non-cancer (HQ > 1 for both adults and children) and cancer (particularly for barley in Bijar) risks for inhabitants via consumption of As contaminated crops cultivated in the study area.

Selenite Foliar Application Alleviates Arsenic Uptake, Accumulation, Migration and Increases Photosynthesis of Different Upland Rice Varieties.

This study investigates how arsenic (As) uptake, accumulation, and migration responds to selenium (Se) foliar application (0-5.0 mg × kg-1). Rice varieties known to accumulate low (DOURADOAGULHA) and high (SINALOAA68) concentrations of arsenic were chosen to grow on soil with different As concentrations (20.1, 65.2, 83.9 mg × kg-1). The results showed that Se of 1.0 mg × L-1 significantly alleviated As stress on upland rice grown on the As-contaminated soil. Under light (65.2 mg × kg-1) and moderate (83.9 mg × kg-1) As concentration treatments, the biomass of upland rice was increased by 23.15% and 36.46% for DOURADOAGULHA, and 46.3% and 54.9% for SINALOAA68. However, the high Se dose (5.0 mg × kg-1) had no significant effect on biomass and heights of upland rice compared to plants where no Se was added. Se significantly decreased As contents in stems and leaves and had different effects on As transfer coefficients for the two rice varieties: when grown on soil with low and moderate As concentrations, Se could reduce the transfer coefficient from stems to leaves, but when grown on the high As soils, this was not the case. The chlorophyll content in plants grown in soil with the moderate concentration of As could be improved by 27.4%-55.3% compared with no Se treatment. Under different As stress, the Se foliar application increased the net photosynthesis, stomatal conductance, and transpiration rate, which meant that Se could enhance the photosynthesis of rice. The intercellular CO2 concentration variation implied that the stomatal or non-stomatal limitations could both occur for different rice varieties under different Se application doses. In conclusion, under moderate As stress, foliar application of Se (1.0 mg × L-1) is recommend to overcome plant damage and As accumulation.

The bioavailability of arsenic species in rice.

Rice is the principal food in many countries for billions of people and one of the most consumed cereals in the world. The rice plant has the ability to bioaccumulate essential and toxic trace elements such as arsenic. The toxicity of the elements depends not only on their concentration but also on their chemical form and their bioavailability. The inorganic forms of arsenic are more toxic than the organic forms and the toxicity increases with decreasing oxidation states. The consumers of rice in Europe who are the most exposed to inorganic arsenic are children under three, thorough diet (rice-based food). Recently, the European Commission established the maximum levels of inorganic arsenic in foodstuffs. This regulation establishes a maximum level of inorganic arsenic of 100 µg kg-1 in rice destined for the production of food for infants and young children. In order to know the relation between the As ingested and the arsenic absorbed, studies of bioavailability are necessary. We proposed an in vitro digestion method with dialysis to estimate this relation. Furthermore, a bioavailability study of As species in rice was performed in order to know if a change in As species occurred during the gastrointestinal digestion process. Arsenic species were determined in rice and in the dialysate fraction by high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The proposed method has been applied to different rice samples acquired in the local Spanish market. Graphical abstract.

A rice glutaredoxin regulate the expression of aquaporin genes and modulate root responses to provide arsenic tolerance.

Rice is the most consumed food crop and essential determinant in global food security program. Currently, arsenic (As) accumulation in rice is a critical concern in terms of both crop productivity and grain quality; therefore, it is an urgent need to reduce As accumulation. Here, we selected a glutaredoxin (OsGrx_C7) gene that plays an essential role in AsIII tolerance in rice. To explore the mechanism, we raised OsGrx_C7 overexpression (OE) rice lines, which showed improved plant AsIII tolerance and lowered its accumulation in grains. Arsenic accumulation in husk, unpolished, and polished rice reduced by ca. 65%, 67%, and 85%, respectively, in OE lines, compared to wild-type (WT) plants. To know the rationale, expression of AsIII transporters (aquaporins) in root and shoot tissues were examined, and revealed that OsGrx_C7 regulates the expression of these genes, which ultimately reduces root to shoot AsIII translocation. Additionally, OsGrx_C7 improves root growth by regulating the expression of oxidative stress-induced root expansion related genes, promote root growth and plant health. Overall, current study suggested that AsIII induced OsGrx_C7 markedly enhanced tolerance to AsIII with reduced accumulation in grains by regulating root expansion and controlling root to shoot As transport by altered expression of AsIII aquaporins.

Elevated Arsenic and Lead Concentrations in Natural Healing Clay Applied Topically as a Treatment for Ulcerative Dermatitis in Mice.

Ulcerative dermatitis in laboratory mice remains an ongoing clinical problem and animal welfare issue. Many products have been used to treat dermatitis in mice, with varying success. Recently, the topical administration of healing clays, such as bentonite and green clays, has been explored as a viable, natural treatment. We found high concentrations of arsenic and lead in experimental samples of therapeutic clay. Given the known toxic effects of these environmental heavy metals, we sought to determine whether the topical administration of a clay product containing bioavailable arsenic and lead exerted a biologic effect in mice that potentially could introduce unwanted research variability. Two cohorts of 20 singly housed, shaved, dermatitis free, adult male CD1 mice were dosed daily for 2 wk by topical application of saline or green clay paste. Samples of liver, kidney and whole blood were collected and analyzed for total arsenic and lead concentrations. Hepatic and renal concentrations of arsenic were not different between treated and control mice in either cohort; however, hepatic and renal concentrations of lead were elevated in clay treated mice compared to controls in both cohorts. In addition, in both cohorts, the activity of δ-aminolevulinate acid dehydratase, an enzyme involved with heme biosynthesis and a marker of lead toxicity, did not differ significantly between the clay-treated mice and controls. We have demonstrated that these clay products contain high concentrations of arsenic and lead and that topical application can result in the accumulation of lead in the liver and kidneys; however, these concentrations did not result in measurable biologic effects. These products should be used with caution, especially in studies of lead toxicity, heme biosynthesis, and renal α2 microglobulin function.

Consequences of trace metal cocktail exposure in zebra finch (Taeniopygia guttata) and effect of calcium supplementation.

Trace metal elements are significant stressors in urban areas. Their harmful effects on physiological parameters are demonstrated, but current laboratory studies are not representative of wild chronic exposure to a trace metal cocktail. Calcium can reduce the accumulation and toxicity of several metals, but soil acidification in cities leads to a decrease in bioavailability of this element. The objective of this study was to investigate the accumulation and toxicity of a trace metal cocktail representative of urban exposure on passerine birds, and test the importance of calcium availability on these toxic effects. We exposed zebra finches (Taeniopygia guttata) to a cocktail of seven metals and one metalloid in drinking water, with or without calcium supplementation. We monitored the concentration of metals in the blood and feathers, and their effects on oxidative status and telomere length. The metal cocktail led to higher concentration of all elements in the feathers, and of arsenic and lead in the blood. Birds with a higher concentration of cadmium, arsenic and lead in the feathers had shorter telomeres, but no impact of the cocktail was detected on oxidative status. Birds of the 'calcium' group and the 'calcium and metal' group accumulated higher concentrations of zinc, chromium and nickel in feathers. The 'calcium and metal' group also accumulated lower concentrations of arsenic and lead in feathers compared to the 'metal' group. Our results suggest that chronic exposure to a cocktail of metals at low concentrations has deleterious effects on birds, which can be limited through calcium intake.

Bioavailable arsenic and amorphous iron oxides provide reliable predictions for arsenic transfer in soil-wheat system.

The application of current soil quality standards based on total arsenic (As) fails to assess the ecological risks of soil arsenic or to ensure the safety of crops and foods. In this study, bioavailable arsenic instead of total arsenic was applied to improve predictive models for arsenic transfer from soil to wheat (Triticum turgidum L.). The stepwise multiple-linear regression analysis showed that bioavailable arsenic and amorphous iron oxides (FeOX) were the two most important factors contributing to arsenic accumulation in wheat grain, with the explained percentage of variation being up to 82%. Compared with the bioavailable arsenic extracted by NH4H2PO4, bioavailable arsenic extracted by HNO3 from soils generated better predictions of the amount of arsenic in grain. The best reliable model was log[Asgrain] = 0.917 log[HNO3-As] - 0.452 log[FeOX] - 1.507 (R2 = 0.82, P <  0.001). Consistently, bioavailable arsenic and FeOX were also the key factors to predict arsenic accumulation in wheat straw, leaves and spikes. Our prediction models was successfully verified for three independent soils. Our results highlight the role of soil bioavailable heavy metals in predicting their transfer in soil-plant systems and can be used to improve existing Chinese soil quality standards.