RESUMO
KEY MESSAGE: Metabolomic and transcriptomic analyses revealed an intensification of energy metabolism in rice grains under DMA stress, possibly causing the consumption of sugars or non-sugars and the development of unfilled grains Excessive dimethylarsinic acid (DMA) causes rice straighthead disease, a physiological disorder typically with erect panicle due to empty grain at maturity. Although the toxicity of DMA and its uptake and transport in rice are well recognized, the underlying mechanism of unfilled grains remains unclear. Therefore, a pot experiment was conducted using a susceptible variety (Ruanhuayou1179, RHY) and a resistant one (Nanjingxiangzhan, NJXZ) via the metabolomic and transcriptomic approaches to explore the mechanisms of empty grains in diseased rice under DMA stress. The results demonstrate an increase in total and methylated As in grains of RHY and NJXZ under DMA addition, with RHY containing higher levels of DMA. DMA addition increased the soluble sugar content in grains of RHY and NJXZ by 17.1% and 14.3% compared to the control, respectively, but significantly reduced the levels of amino acid, soluble protein, and starch. The decrease of grain Zn and B contents was also observed, and inadequate Zn might be a key factor limiting rice grain yield under DMA stress. Notably, DMA addition altered the expression levels of genes involved in the transport of sugar, amino acids, nitrates/peptides, and mineral ions. In sugar and amino acid metabolism, the reduction of metabolites and the upregulated expression of genes reflect positive regulation at the level of energy metabolism, implying that the reduction of grain starch and proteins might be ascribed to generate sufficient energy to resist the stress. This study provides a useful reference for understanding the molecular mechanism of grain emptying under DMA stress.
Assuntos
Aminoácidos , Ácido Cacodílico , Regulação da Expressão Gênica de Plantas , Oryza , Estresse Fisiológico , Oryza/genética , Oryza/metabolismo , Oryza/efeitos dos fármacos , Aminoácidos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácido Cacodílico/metabolismo , Grão Comestível/metabolismo , Grão Comestível/genética , Grão Comestível/efeitos dos fármacos , Micronutrientes/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Zinco/metabolismoRESUMO
The arsenic (As) content of seaweed has been extensively studied due to its toxicological concerns. As a primary producer, seaweed plays a vital role in the biochemical cycling of As in marine environments. Several studies have focused on the growth and behavior of seaweed under a salinity gradient; however, information related to the impact of salinity on As uptake, biotransformation mechanism, and time-dependent speciation patterns of these plants is limited. This study aimed to investigate the temporal effects of salinity on these factors in seaweed. Three seaweed species, Sargassum fusiforme, Sargassum thunbergii, and Sargassum horneri, were maintained in a 1% Provasoli-enriched seawater medium for 14 d under 5, 15, 25, and 34 salinities. The results revealed that the high salinity media promoted a rapid uptake of As by all three species. Arsenic accumulation inside the cell approached 100% within seven days of culture for S. thunbergii, irrespective of the salinity content of the media. In addition, As(V) biotransformation and release by S. fusiforme and S. thunbergii were time-dependent, while S. horneri released dimethylarsinic acid (DMAA) from day 3 of the culture. All seaweed species showed methylation of As(V) to DMAA during the culture period. Furthermore, S. thunbergii released DMAA when As(V) was completely depleted from the culture media, whereas the release by S. fusiforme and S. horneri was relatively earlier than that of S. thunbergii. S. horneri showed minimal tolerance to low salinity, as the cells revealed significant damage. Based on the results of this study, a conceptual model was developed that demonstrated the effects of salinity on As uptake and the biotransformation mechanism of seaweed.
Assuntos
Arsênio , Biotransformação , Salinidade , Sargassum , Alga Marinha , Poluentes Químicos da Água , Sargassum/metabolismo , Arsênio/metabolismo , Alga Marinha/metabolismo , Poluentes Químicos da Água/metabolismo , Água do Mar/química , Ácido Cacodílico/metabolismoRESUMO
Rice straighthead disease substantially reduces crop yield, posing a significant threat to global food security. Dimethylarsinic acid (DMA) is the causal agent of straighthead disease and is highly toxic to the reproductive tissue of rice. However, the precise physiological mechanism underlying DMA toxicity remains unknown. In this study, six rice varieties with varying susceptibility to straighthead were utilized to investigate the growth performance and element distribution in rice panicles under DMA stress through pot experiments, as well as to explore the physiological response to DMA using transcriptomic methods. The findings demonstrate significant variations in both DMA accumulation and straighthead sensitivity among cultivars. The susceptible varieties exhibited higher DMA accumulation indices and displayed typical symptoms of straighthead disease, including erect panicles, deformed rachides and husks, and reduced seed setting rate and grain yield when compared to the resistant varieties. Moreover, DMA addition promoted mineral nutrients to accumulate in rachides and husks but less in grains. DMA showed preferential accumulation in rice grains with a distribution pattern similar to that of Copper (Cu) and zinc (Zn) within the panicle. Transcriptome analyses underscored the substantial impact of DMA on gene expression related to mineral metabolism. Notably, DMA addition significantly up-regulated the expression of pectin methylesterase, pectin lyase, polygalacturonase, and exogalacturonase genes in Nanjingxiangzhan, while these genes were down-regulated or weakly expressed in Ruanhuayou 1179. The alteration of pectin metabolic pathways induced by DMA may lead to abnormality of cell wall assembly and modification, thereby resulting in deformed rice panicles.
Assuntos
Oryza , Oryza/metabolismo , Sementes/metabolismo , Grão Comestível , Ácido Cacodílico/metabolismo , Minerais/metabolismoRESUMO
Dimethylarsenate [DMAs(V)] can be produced by some soil microorganisms through methylation of inorganic arsenic (As), especially in anoxic paddy soils. DMAs(V) is more phytotoxic than inorganic As and can cause the physiological disorder straighthead disease in rice. Rice cultivars vary widely in the resistance to DMAs(V), but the mechanism remains elusive. Here, we investigated the differences in DMAs(V) uptake, translocation, and reduction to dimethylarsenite [DMAs(III)], as well as the effects on the metabolome, between two rice cultivars Mars and Zhe733. We found that Mars was 11-times more resistant to DMAs(V) than Zhe733. Mars accumulated more DMAs(V) in the roots, whereas Zhe733 translocated more DMAs(V) to the shoots and reduced more DMAs(V) to DMAs(III). DMAs(III) was more toxic than DMAs(V). Using heterologous expression and in vitro enzyme assays, we showed that the glutathione-S-transferases OsGSTU17 and OsGSTU50 were able to reduce DMAs(V) to DMAs(III). The expression levels of OsGSTU17 and OsGSTU50 were higher in the shoot of Zhe733 compared to Mars. Metabolomic analysis in rice shoots showed that glutathione (GSH) metabolism was perturbed by DMAs(V) toxicity in Zhe733. Application of exogenous GSH significantly alleviated the toxicity of DMAs(V) in Zhe733. Taken together, the results suggest that Mars is more resistant to DMAs(V) than Zhe733 because of a lower root-to-shoot translocation and a smaller capacity to reduce DMAs(V) to DMAs(III).
Assuntos
Arsênio , Arsenicais , Oryza , Poluentes do Solo , Ácido Cacodílico/metabolismo , Oryza/metabolismo , Arsenicais/metabolismo , Metilação , Glutationa/metabolismo , Solo , Arsênio/toxicidade , Arsênio/metabolismoRESUMO
Perfluorooctanoic acid (PFOA) and arsenic are widely distributed pollutants and can coexist in the environment. However, no study has been reported about the effects of different arsenic species on the joint toxicity of arsenic and PFOA to soil invertebrates. In this study, four arsenic species were selected, including arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA). Earthworms Eisenia fetida were exposed to soils spiked with sublethal concentrations of PFOA, different arsenic species, and their binary mixtures for 56 days. The bioaccumulation and biotransformation of pollutants, as well as eight biomarkers in organisms, were assayed. The results indicated that the coexistence of PFOA and different arsenic species in soils could enhance the bioavailability of arsenic species while reducing the bioavailability of PFOA, and inhibit the arsenic biotransformation process in earthworms. Responses of most biomarkers in joint treatments of PFOA and As(III)/As(V) showed more significant variations compared with those in single treatments, indicating higher toxicity to the earthworms. The Integrated Biomarker Response (IBR) index was used to integrate the multi-biomarker responses, and the results also exhibited enhanced toxic effects in combined treatments of inorganic arsenic and PFOA. In comparison, both the biomarker variations and IBR values were lower in joint treatments of PFOA and MMA/DMA. Then the toxic interactions in the binary mixture systems were characterized by using a combined method of IBR and Effect Addition Index. The results revealed that the toxic interactions of the PFOA/arsenic mixture in earthworms depended on the different species of arsenic. The combined exposure of PFOA with inorganic arsenic led to a synergistic interaction, while that with organic arsenic resulted in an antagonistic response. Overall, this study provides new insights into the assessment of the joint toxicity of perfluoroalkyl substances and arsenic in soil ecosystems.
Assuntos
Arsênio , Arsenicais , Poluentes Ambientais , Fluorocarbonos , Oligoquetos , Poluentes do Solo , Animais , Arsênio/análise , Ecossistema , Arsenicais/metabolismo , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Ácido Cacodílico/metabolismo , Poluentes Ambientais/metabolismo , Biomarcadores/metabolismo , Solo , Poluentes do Solo/análiseRESUMO
Bacteria are candidates for the biotransformation of environmental arsenic (As), while As metabolism in bacteria is not yet fully understood. In this study, we sequenced the genome of an As-resistant bacterium strain Stenotrophomonas maltophilia SCSIOOM isolated from the fish gut. After arsenate (As(V)) exposure, S. maltophilia transformed As(V) to organoarsenicals, along with the significant change of the expression of 40 genes, including the upregulation of arsH, arsRBC and betIBA. The heterogeneous expression of arsH and arsRBC increased As resistance of E. coli AW3110 by increasing As efflux and transformation. E. coli AW3110 (pET-betIBA) could transform inorganic As into dimethylarsinate (DMA) and nontoxic arsenobetaine (AsB), which suggested that AsB could be synthesized through the synthetic pathway of its analog-glycine betaine. In addition, the existence of arsRBC, betIBA and arsH reduced the reactive oxygen species (ROS) induced by As exposure. In total, these results demonstrated that S. maltophilia adopted an As metabolism strategy by reducing As accumulation and synthesizing less toxic As species. We first reported the production and potential synthetic pathway of AsB in bacteria, which improved our knowledge of As toxicology in microorganisms.
Assuntos
Arsênio , Stenotrophomonas maltophilia , Animais , Arseniatos/metabolismo , Arseniatos/toxicidade , Arsênio/metabolismo , Arsênio/toxicidade , Arsenicais , Betaína/metabolismo , Ácido Cacodílico/metabolismo , Escherichia coli/metabolismo , Peixes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Stenotrophomonas maltophilia/metabolismoRESUMO
Elevated concentrations of total arsenic (As) have been reported in boreal freshwater fish in both human-impacted and relatively pristine areas. We assessed the arsenic speciation profiles in muscle tissue of six fish species (n = 300) sampled from nine locations across a remote freshwater watershed in northern Ontario, Canada, extending from inland headwater lakes to the coastal marine confluence. Of the five arsenic species measured, only arsenobetaine (AsB) and dimethylarsinic acid (DMA) were detected in these fish. Riverine fish had up to 10-fold higher total [As] when compared to lacustrine fish. On average, these riverine fish also had higher percentages of AsB (%AsB, 60 ± 26%) and lower percentages of unmeasured arsenic (%UNM, 20 ± 21%), compared to lacustrine fish (28 ± 18% and 52 ± 21% %AsB and %UNM, respectively). DMA percentages (%DMA) were relatively consistent across the watershed, averaging 20 ± 21% across all fish. We examined ecological drivers of As speciation and found that %AsB increased slightly with fish weight in large-body predatory fish, but not in forage fish or insectivores. Furthermore, %AsB was positively related to trophic elevation (inferred from δ15N) in lacustrine fish across 3 out of 4 communities and within some populations. Lastly, riverine fish with a more marine-based diet had markedly higher %AsB when compared to fish with more freshwater-based diets, indicating an effect of anadromy on arsenic speciation. Overall, knowledge on arsenic speciation in freshwater fish has been limited and these results indicate potential drivers that can be considered in future studies. Furthermore, the absence of toxic inorganic As species in these boreal fish is an important consideration for future environmental monitoring practices and risk assessments, some of which assume 10-20% of total [As] in fish is present as toxic inorganic As. Additional studies on As bioaccumulation and biotransformation are needed in freshwater systems, particularly at the base of aquatic food webs.
Assuntos
Intoxicação por Arsênico , Arsênio , Arsenicais , Animais , Arsênio/análise , Arsenicais/metabolismo , Ácido Cacodílico/metabolismo , Peixes/metabolismo , Humanos , Lagos , Músculos/química , OntárioRESUMO
Arsenic, as a human carcinogen, has posed a certain threat to environmental health globally. However, the underlying mechanism of the arsenic carcinogenic effect remains largely undetermined. The up-regulation of MDM2 seems to play a crucial part in tumors in especial carcinomas of the diffuse type. The interaction of MDM2 and p53 is closely relevant to the pathogenesis of tumors. In this study, we aimed to investigate the effect on MDM2, p53, and their phosphorylation after As(III). In the epidemiological study, we investigated that MDM2 expression was up-regulation and was positively linked to methylated metabolites (monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) after As(III)-exposure. In vitro studies employing A549 and 16HBE cells confirmed the epidemiological data. Studies on MDM2 phosphorylation sites consisting of Ser166, Ser260, and Ser394 in response to arsenic exposure, which have not been studied presently, indicated that As(III) could induce the expression of MDM2 phosphorylation. Moreover, we studied the alterations of p53 and its N-terminus phosphorylation sites of Ser9, Ser15, and Ser33, which demonstrated that p53 and its phosphorylation were highly expressed after As(III) exposure. Subsequently, Co-immunoprecipitation assays validated our hypothesis that the bonding of MDM2 and p53 was altered by arsenic exposure. What's more, outcomes coming from different cell types of A549, 16HBE, and 60 T-16HBE revealed that MDM2 and its phosphorylation expression existed a significant difference. The study provides evidence that As(III) and its methylated metabolites modulate the expression of MDM2, p53, and their phosphorylation and then affect the interaction between MDM2 and p53.
Assuntos
Intoxicação por Arsênico , Arsênio , Arsenicais , Humanos , Arsênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fosforilação , Arsenicais/metabolismo , Ácido Cacodílico/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismoRESUMO
In order to understand the mechanisms of arsenic (As) accumulation and detoxification in aquatic plants exposed to different As species, a hydroponic experiment was conducted and the three aquatic plants (Hydrilla verticillata, Pistia stratiotes and Eichhornia crassipes) were exposed to different concentrations of As(III), As(V) and dimethylarsinate (DMA) for 10 days. The biomass, the surface As adsorption and total As adsorption of three plants were determined. Furthermore, As speciation in the culture solution and plant body, as well as the arsenate reductase (AR) activities of roots and shoots, were also analyzed. The results showed that the surface As adsorption of plants was far less than total As absorption. Compared to As(V), the plants showed a lower DMA accumulation. P. stratiotes showed the highest accumulation of inorganic arsenic but E. crassipes showed the lowest at the same As treatment. E. crassipes showed a strong ability to accumulate DMA. Results from As speciation analysis in culture solution showed that As(III) was transformed to As(V) in all As(III) treatments, and the oxidation rates followed as the sequence of H. verticillata>P. stratiotes>E. crassipes>no plant. As(III) was the predominant species in both roots (39.4-88.3%) and shoots (39-86%) of As(III)-exposed plants. As(V) and As(III) were the predominant species in roots (37-94%) and shoots (31.1-85.6%) in As(V)-exposed plants, respectively. DMA was the predominant species in both roots (23.46-100%) and shoots (72.6-100%) in DMA-exposed plants. The As(III) contents and AR activities in the roots of P. stratiotes and in the shoots of H. verticillata were significantly increased when exposed to 1 mg·L-1 or 3 mg·L-1 As(V). Therefore, As accumulation mainly occurred via biological uptake rather than physicochemical adsorption, and AR played an important role in As detoxification in aquatic plants. In the case of As(V)-exposed plants, their As tolerance was attributed to the increase of AR activities.
Assuntos
Araceae , Arseniato Redutases/metabolismo , Arsênio , Ácido Cacodílico , Eichhornia , Hydrocharitaceae , Proteínas de Plantas/metabolismo , Poluentes Químicos da Água , Adsorção , Araceae/química , Araceae/metabolismo , Arsênio/química , Arsênio/metabolismo , Ácido Cacodílico/química , Ácido Cacodílico/metabolismo , Eichhornia/química , Eichhornia/metabolismo , Hydrocharitaceae/química , Hydrocharitaceae/metabolismo , Hidroponia , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Brotos de Planta/química , Brotos de Planta/metabolismo , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismoRESUMO
Water management is an economic and effective strategy to reduce arsenic (As) accumulation in rice grains, but little is known about the effect of water management on the migration and transformation of As in the soil-rice system. In this study, the effect of the continually (CF) and intermittent flooding (IF) treatments on the dynamic change of As in the rhizosphere soil-pore water-iron plaque-rice system was systematically investigated using pot experiments. The expressions of genes involved in As uptake and translocation in rice plants under different water management treatments were further examined. Results showed that the total As concentration in brown rice was increased by 50.8% in the CF treatment compared to the IF treatment, and dimethylarsinic acid (DMA) made greater contribution (from 15.5% to 29.2%) to total As increase in brown rice under the CF treatment. The CF treatment increased As bioavailability in the rhizosphere soil and soil pore water, which enhanced As uptake and transport to the xylem in rice plants by inducing the expressions of silicon transporter genes (OsLsi1 and OsLsi2) compared to the IF treatment. Moreover, the CF treatment increased As translocation from roots to shoots by reducing soil available sulfur and phytochelatins (PCs) biosynthesis and vacuolar sequestration in rice roots compared with the IF treatment. The study provides insight into the physiological and molecular mechanisms underlying As uptake and translocation in rice plants under different water regimes, which will be helpful for adopting the irrigation technique to mitigate excessive As accumulation in rice grains and associated health risk to humans.
Assuntos
Irrigação Agrícola/métodos , Arsênio/metabolismo , Proteínas de Membrana Transportadoras/genética , Oryza/metabolismo , Poluentes do Solo/metabolismo , Compostos de Sulfidrila/metabolismo , Poluentes Químicos da Água/metabolismo , Arsênio/análise , Disponibilidade Biológica , Transporte Biológico , Ácido Cacodílico/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Humanos , Ferro/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Oryza/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Rizosfera , Solo/química , Poluentes do Solo/análise , Poluentes Químicos da Água/análiseRESUMO
This study assesses arsenic (As) fractionation in sediments and speciation in muscle tissues of Bagrid catfish, Chrysichthys nigrodigitatus from Lagos Lagoon, southwest Nigeria to determine risks to ecological receptors and humans. Residual As was the predominant geochemical fraction (86.2%) in sediments. Arsenite [As (III)] concentrations which ranged from 0.06 to 0.53 mg kg-1 in catfish muscle tissue, accounting for 25.9% of total As was the dominant species. Less toxic dimethylarsinic acid (DMA) which varied between 0.06 and 0.27 mg kg-1 made up to 10.8% of total As in catfish muscle tissue. Estimated human average daily intake (ADI) of As as As (III) and DMA were 1.35 × 10-4 and 0.62 × 10-4 mg kg-1 BW with corresponding hazard quotients (HQs) of 0.45 and 0.21, respectively, indicate no apparent health hazard to adult consumers. The incremental lifetime cancer risks (ILCR) of 0.78 × 10-3 for total As, 0.20 × 10-3 for As (III), and 0.93 × 10-3 for DMA, for adults from the consumption of catfish is slightly higher than the US EPA threshold and indicates moderate carcinogenic risk. Furthermore, 12.5% bioavailable fraction of As in sediment and relatively higher levels of As (III) in fish tissues has ecological and public health implications.
Assuntos
Arsênio/análise , Ácido Cacodílico/análise , Peixes-Gato/metabolismo , Sedimentos Geológicos/química , Músculos/metabolismo , Poluentes Químicos da Água/análise , Adulto , Animais , Arsênio/metabolismo , Ácido Cacodílico/metabolismo , Humanos , Nigéria , Medição de Risco , Poluentes Químicos da Água/metabolismoRESUMO
The role of water and bottom sediment pollution of a river subjected to a strong industrial anthropo-pressure in coastal plants was investigated. The work presented the influence of polluted environment on accumulation of metal(loid)s (including arsenic and its species) in Stuckenia pectinata L., Galium aparine L., and Urtica dioica L. The study provided important information on the contents of organic and inorganic arsenic species in selected plants and their response to heavy metal and arsenic contamination. The As(III), As(V), AB (arsenobetaine), MMA (monomethylarsonic acid), and DMA (dimethylarsinic acid) ions were successfully separated on the Hamilton PRP-X100 column with high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) techniques. The Pollution Load Index and geo-accumulation Index (Igeo) values clearly indicate significant pollution of the examined ecosystem with heavy metals. The chemometric analysis with the concepts of (Dis)similarity Analysis, Cluster Analysis, and Principal Component Analysis helped to visualize the variability of the As species concentrations and to analyse correlations between sampling point locations and analyte contents.
Assuntos
Arsenicais/análise , Bioacumulação , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Plantas/efeitos dos fármacos , Rios/química , Poluentes Químicos da Água/análise , Arsenicais/metabolismo , Ácido Cacodílico/análise , Ácido Cacodílico/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ecossistema , Galium/efeitos dos fármacos , Galium/crescimento & desenvolvimento , Galium/metabolismo , Espectrometria de Massas/métodos , Plantas/metabolismo , Polônia , Urtica dioica/efeitos dos fármacos , Urtica dioica/crescimento & desenvolvimento , Urtica dioica/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Inorganic arsenic (iAs) is an environmental diabetogen, but mechanisms underlying its diabetogenic effects are poorly understood. Exposures to arsenite (iAsIII) and its methylated metabolites, methylarsonite (MAsIII) and dimethylarsinite (DMAsIII), have been shown to inhibit glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cells and isolated pancreatic islets. GSIS is regulated by complex mechanisms. Increase in ATP production through metabolism of glucose and other substrates is the ultimate trigger for GSIS in ß-cells. In the present study, we used metabolomics to identify metabolites and pathways perturbed in cultured INS-1 832/13 rat insulinoma cells and isolated murine pancreatic islets by exposures to iAsIII, MAsIII and DMAsIII. We found that the exposures perturbed multiple metabolites, which were enriched primarily in the pathways of amino acid, carbohydrate, phospholipid and carnitine metabolism. However, the effects of arsenicals in INS-1 832/13 cells differed from those in the islets and were exposure specific with very few overlaps between the three arsenicals. In INS-1 832/13 cells, all three arsenicals decreased succinate, a metabolite of Krebs cycle, which provides substrates for ATP synthesis in mitochondria. Acetylcarnitine was decreased consistently by exposures to arsenicals in both the cells and the islets. Acetylcarnitine is usually found in equilibrium with acetyl-CoA, which is the central metabolite in the catabolism of macronutrients and the key substrate for Krebs cycle. It is also thought to play an antioxidant function in mitochondria. Thus, while each of the three trivalent arsenicals perturbed specific metabolic pathways, which may or may not be associated with GSIS, all three arsenicals appeared to impair mechanisms that support ATP production or antioxidant defense in mitochondria. These results suggest that impaired ATP production and/or mitochondrial dysfunction caused by oxidative stress may be the mechanisms underlying the inhibition of GSIS in ß-cells exposed to trivalent arsenicals.
Assuntos
Arsenitos/toxicidade , Ácido Cacodílico/análogos & derivados , Metabolismo Energético/efeitos dos fármacos , Insulinoma/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Metaboloma , Neoplasias Pancreáticas/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Arsenitos/metabolismo , Biotransformação , Ácido Cacodílico/metabolismo , Ácido Cacodílico/toxicidade , Linhagem Celular Tumoral , Insulinoma/patologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Metabolômica , Metilação , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Ratos , Técnicas de Cultura de TecidosRESUMO
Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.
Assuntos
Arseniatos/urina , Arsenicais/urina , Arsenitos/urina , Ácido Cacodílico/urina , Deficiências do Desenvolvimento/sangue , Ácido Fólico/sangue , Vitamina B 12/sangue , Arseniatos/metabolismo , Arsenicais/metabolismo , Arsenitos/metabolismo , Ácido Cacodílico/metabolismo , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/urina , Feminino , Humanos , Masculino , Metilação , Razão de Chances , TaiwanRESUMO
Chronic exposure to inorganic arsenic (iAs), a common drinking water and food contaminant, has been associated with an increased risk of type 2 diabetes in population studies worldwide. Several mechanisms underlying the diabetogenic effects of iAs have been proposed through laboratory investigations. We have previously shown that exposure to arsenite (iAs(III)) or its methylated trivalent metabolites, methylarsonite (MAs(III)) and dimethylarsinite (DMAs(III)), inhibits glucose-stimulated insulin secretion (GSIS) in pancreatic islets, without significant effects on insulin expression or insulin content. The goal of the present study was to determine if iAs(III) and/or its metabolites inhibit Ca2+ influx, an essential mechanism that regulates the release of insulin from ß cells in response to glucose. We found that in vitro exposures for 48 h to non-cytotoxic concentrations of iAs(III), MAs(III), and DMAs(III) impaired Ca2+ influx in isolated murine pancreatic islets stimulated with glucose. MAs(III) and DMAs(III) were more potent inhibitors of Ca2+ influx than iAs(III). These arsenicals also inhibited Ca2+ influx and GSIS in islets treated with depolarizing levels of potassium chloride in the absence of glucose. Treatment with Bay K8644, a Cav1.2 channel agonist, did not restore insulin secretion in arsenical-exposed islets. Tolbutamide, a KATP channel blocker, prevented inhibition of insulin secretion in MAs(III)- and DMAs(III)-exposed islets, but only marginally in islets exposed to iAs(III). Our findings suggest that iAs(III), MAs(III), and DMAs(III) inhibit glucose-stimulated Ca2+ influx in pancreatic islets, possibly by interfering with KATP and/or Cav1.2 channel function. Notably, the mechanisms underlying inhibition of GSIS by iAs(III) may differ from those of its trivalent methylated metabolites.
Assuntos
Arsenitos/toxicidade , Ácido Cacodílico/análogos & derivados , Cálcio/metabolismo , Glucose/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Arsenitos/metabolismo , Ácido Cacodílico/metabolismo , Ácido Cacodílico/toxicidade , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Ilhotas Pancreáticas/metabolismo , Canais KATP/metabolismo , Masculino , Metilação , Camundongos Endogâmicos C57BL , Poluentes Químicos da Água/metabolismoRESUMO
Speciation transformation of arsenic in the abalone viscera hydrolysate fraction (AVHF) was evaluated using in vitro and in vivo methods to determine its safety given that AVHF is rich in arsenic. The dimethylarsinic acid (DMA) proportion and some free amino acid contents increased, whereas arsenobetaine (AB) proportion decreased when AVHF was digested by pepsin. However, molecular weight distribution was unchanged, and no obvious changes were found in the intestinal medium. In the single-dose experiment, the AB concentration on the mouse plasma rapidly increased, which reached up to 12.53â¯ng/mL in 2â¯h after the administration of AVHF (10â¯g/kg body weight) and reduced to half of the maximum at 8â¯h after administration. Furthermore, alanine (Ala) content in the urine of mice increased at 8â¯h after AVHF administration, suggesting that Ala might be chelated with arsenic and could not be absorbed well. Long-term experiments showed that AB was not accumulated in mice tissue/organ. However, some AB could be converted into DMA, which was mainly accumulated in mice hair. The in vivo experiments also suggested that the AVHF is safe as health food.
Assuntos
Arsênio/administração & dosagem , Alimentos Marinhos/análise , Vísceras/metabolismo , Alanina/metabolismo , Aminoácidos/metabolismo , Animais , Arsênio/farmacocinética , Arsenicais/metabolismo , Ácido Cacodílico/metabolismo , Feminino , Inocuidade dos Alimentos , Cabelo/química , Hidroxiprolina/metabolismo , Limite de Detecção , Camundongos , Peso Molecular , Distribuição TecidualRESUMO
The bioaccessibility and speciation of arsenic (As) in rice grains have been investigated by the physiologically based extraction test (PBET) method. A total of 42 rice samples were collected from Hunan Province, a typical mine-impacted province in China. The bioaccessibility in the gastrointestinal tract was 71.7⯱â¯13.5% for the collected rice grains. Arsenite [As(III)] was the predominant As species in the simulated gastric and gastrointestinal solutions, followed by dimethylarsinic acid (DMA), arsenate [As(V)] and monomethylarsonic acid (MMA). The bioaccessible As(V) was irrelevant to As(V) in the rice grains, suggesting that interconversion between As(V) and other species was occurred in the simulated gastrointestinal tract. Monte-Carlo simulation was introduced to assess the health risk from exposure to inorganic As. The average values for target hazard quotient (THQ) and bioaccessible THQ were 2.704 and 1.637, respectively. The inclusion of bioaccessibility reduced the probability of non-carcinogenic health risk from 97.32% to 76.86%.
Assuntos
Arsenicais/metabolismo , Oryza/química , Arsênio/metabolismo , Arsenicais/análise , Arsenitos/metabolismo , Ácido Cacodílico/metabolismo , Humanos , Espectrometria de Massas , Método de Monte Carlo , Oryza/metabolismo , Medição de RiscoRESUMO
Arsenic species contaminate food and water, with typical dietary intake below 1⯵g/kgâ¯bw/d. Exposure to arsenic in heavily contaminated drinking water is associated with human diseases, including cardiovascular and respiratory disorders, diabetes, and cancer. Dietary intake assessments show that rice and seafood are the primary contributors to intake of both inorganic arsenic and dimethylarsinic acid (DMAV) and at similar magnitudes. DMAV plays a central role in the toxicology of arsenic because enzymatic methylation of arsenite produces DMAV as the predominant metabolite, which may promote urinary clearance but also generates reactive intermediates, predominantly DMAIII, that bind extensively to cellular thiols. Both inorganic arsenic and DMAV are carcinogenic in chronically exposed rodents. This study measured pentavalent and trivalent arsenic species in blood and tissues after oral and intravenous administration of DMAV (50⯵g As/kg bw). DMAV underwent extensive first-pass metabolism in the intestine and liver, exclusively by reduction to DMAIII, which bound extensively to blood and tissues. The results confirm a role for methylation-independent reductive metabolism in producing fluxes of DMAIII that presumably underlie arsenic toxicity and indicate the need to include all dietary intake of inorganic arsenic and DMAV in risk assessments.
Assuntos
Ácido Cacodílico/metabolismo , Administração Oral , Animais , Ácido Cacodílico/administração & dosagem , Ácido Cacodílico/farmacocinética , Eritrócitos/metabolismo , Feminino , Injeções Intravenosas , CamundongosRESUMO
The effects on juvenile rainbow trout survival, growth, food consumption, and food conversion efficiency from dietborne exposures to inorganic arsenic (arsenite, arsenate) and to the organoarsenicals monomethylarsonate (MMA), dimethylarsinate (DMA), and arsenobetaine (AsB) were investigated in two experiments: (1) a 28-d exposure using live diets of oligochaete worms separately exposed via water to these five arsenic compounds and (2) a 56-d exposure using pellet diets prepared from commercial fish food to which arsenite, MMA, or DMA were added. In the live diet experiment, the degree to which worms could be contaminated with the organoarsenicals was limited by toxicity to the worms and other experimental constraints, so that their toxicity relative to inorganic arsenic could not be fully established, but AsB was concluded to have low toxicity, consistent with published results for mammals. For the pellet diet experiment, MMA and DMA were found to be at least an order of magnitude less toxic than inorganic As on the basis of concentration in the diet, as well as much less toxic on the basis of accumulation in the fish. The need to consider speciation in aquatic risk assessments for arsenic was further demonstrated by tissue analyses of three macroinvertebrate species from a mining-impacted stream, which showed large variations in both total arsenic and the relative amounts of inorganic and organic arsenic. Additionally, although effects of arsenic on trout appear to be well correlated with inorganic arsenic, worms were found to be more sensitive to waterborne DMA than to inorganic arsenic, showing that low toxicity of organoarsenicals cannot be assumed for all aquatic organisms. Various difficulties in evaluating and applying studies on dietborne exposures and fish growth are also discussed.
Assuntos
Arsenicais/metabolismo , Oligoquetos/metabolismo , Oncorhynchus mykiss/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Arseniatos/metabolismo , Arseniatos/toxicidade , Arsenitos/metabolismo , Arsenitos/toxicidade , Ácido Cacodílico/metabolismo , Ácido Cacodílico/toxicidade , Dieta , Cadeia Alimentar , Mineração , Rios/química , Poluentes Químicos da Água/metabolismoRESUMO
High arsenic (As) concentrations are found in marine clams, usually as less-toxic arsenobetaine (AsB). However, when clams were exposed to elevated As concentrations in the environments, As species distribution within them may be altered. This study aimed to determine As bioaccumulation and biotransformation in marine clams (Asaphis violascens) along As concentration gradients for 10 days. Nine treatments of dissolved As exposure [control, 1, 3 (low), 10, 20 (high) mg/L As(III) and As(V)] were performed. Clams could biotransform low-levels of inorganic As efficiently, while they had lower biotransformation efficiencies when exposed to high As concentrations. AsB decreased with increasing As(III) and As(V) concentrations, while dimethylarsinic acid exhibited as a predominant As species in 3 mg/L exposure treatments. These results suggested that As methylation, synthesis and/or degradation of AsB should be affected by exposure concentrations. Therefore, these toxic As species within clams may cause a potential toxicological hazard to human beings.