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1.
Chemosphere ; 238: 124647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31466007

RESUMO

Ground water arsenic contamination is a global menace. Since arsenic may affect the immune system, leading to immunesuppression, we investigated the effects of acute arsenic exposure on the thymus and spleen using Swiss albino mice, exposed to 5 ppm, 15 ppm and 300 ppm of sodium arsenite for 7 d. Effects on cytokine balance and cell survivability were subsequently analyzed. Our data showed that arsenic treatment induced debilitating alterations in the tissue architecture of thymus and spleen. A dose-dependent decrease in the ratio of CD4+-CD8+ T-cells was observed along with a pro-inflammatory response and redox imbalance. In addition, pioneering evidences established the ability of arsenic to induce an up regulation of Hsp90, eventually resulting in stabilization of its client protein Beclin-1, an important autophagy-initiating factor. This association initiated the autophagic process, confirmed by co-immunoprecipitation assay, acridine orange staining and Western blot, indicating the effort of cells trying to survive at lower doses. However, increased arsenic assault led to apoptotic cell death in the lymphoid organs, possibly by increased ROS generation. There are several instances of autophagy and apoptosis taking place either simultaneously or sequentially due to oxidative stress. Since arsenic is a potent environmental stress factor, exposure to arsenic led to a dose-dependent increase in both autophagy and apoptosis in the thymus and spleen, and cell death could therefore possibly be induced by autophagy. Therefore, exposure to arsenic leads to serious effects on the immune physiology in mice, which may further have dire consequences on the health of exposed animals.


Assuntos
Arsênico/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arsenitos/farmacologia , Relação CD4-CD8 , Inflamação/induzido quimicamente , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
2.
Immunopharmacol Immunotoxicol ; 41(4): 513-520, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31397191

RESUMO

Exposure to environmentally relevant doses of arsenic has several harmful effects on the human immune system. In traditional Eastern medicines, nettle has been used as an anti-inflammatory agent to treat rheumatism and osteoarthritis. Fumaric acid (FA) as a major effective compound in nettle was chosen based on very accurate virtual screening to find antagonist for TLR4/MD structure. In this study, the in vitro therapeutic effects of FA on arsenic-exposed monocytes-derived dendritic cells (MDDCs) were evaluated. All the canonical functions of dendritic cells in bridging innate and adaptive immune system including phagocytosis and antigen-presenting capacity, and also cytokines secretion, were evaluated after exposure to arsenic/FA. FA profoundly over-expressed antigen-presenting capacity of MDDCs after exposure to arsenic through the upregulation of MHCιι. However, phagocytosis capacity of arsenic-exposed MDDCs is not compensated for, by treatment with FA. Arsenic up-regulates pro-inflammatory cytokines independents of TLR4 pathway. FA surprisingly mitigates the up-regulation of IL-1ß and TNF-α but not TLR4 and NF-kB. Moreover, FA increases the viability of MDDCs even at a high dose of arsenic. Totally, FA reduced inflammatory factors induced by arsenic. This finding confirmed that nettle and other medicinal plants containing similar structures with FA could be further analyzed as valuable candidates for the reduction of drastic effects of arsenic in human immune systems.


Assuntos
Arsênico/farmacologia , Células Dendríticas/efeitos dos fármacos , Fumaratos/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Monócitos/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Imunidade Adaptativa/efeitos dos fármacos , Adulto , Apresentação do Antígeno/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Monócitos/metabolismo , Fagocitose/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
3.
Pak J Pharm Sci ; 32(3): 957-962, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278706

RESUMO

Realgar as a kind of arsenic agent is currently used to treat APL in China. The effectiveness and low toxicity of realgar have been verified, lower than arsenic trioxide. Although the therapeutic efficacy of realgar is blocked severely by its poor insolubility in water. In our lab, we addressed this problem by obtaining realgar bioleaching solution (RBS) from microbiological leaching technique. To develop a tradition Chinese medicinal formula (TCMF) for clinical application realgar is usually used with other herbs. However, treated realgar with RBS has not been evaluated in TCMF contain realgar. In the present study we used NB4 to investigate the effects of novel Realgar-Indigo naturalis formula (FRBS) on cell proliferation and apoptosis. We used MTT assay to measure anti proliferative activity of FRBS. We further study the effects of FRBS on cell growth and apoptosis according flow cytometry, DNA fragmentation assay and Fluorescence microscopy and Western blot. The results revealed that FRBS significantly inhibited growth in a dose-dependent manner, and induced apoptosis in NB4 cells. NB4 cell inhibitory response to FRBS at 2µg ml-1 of arsenic concentration was twofold higher, dissimilar to RIF, and induced apoptosis more effectively. Further, a higher expression of caspase-3, caspase-9 and cytochrome C from increased from FRBS. RBS can substitute the traditional realgar powder in RIF in order to provide a novel and promising Realgar-Indigo naturalis formula to treat acute promyelocytic leukemia.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Arsênico/administração & dosagem , Arsênico/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia
4.
Arch Microbiol ; 201(9): 1285-1293, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256199

RESUMO

Aiming at revealing the arsenic (As) resistance of the endophytic Kocuria strains isolated from roots and stems of Sphaeralcea angustifolia grown at mine tailing, four strains belonging to different clades of Kocuria based upon the phylogeny of 16S rRNA genes were screened for minimum inhibitory concentration (MIC). Only the strain NE1RL3 was defined as an As-resistant bacterium with MICs of 14.4/0.0125 mM and 300/20.0 mM for As3+ and As5+, respectively, in LB/mineral media. This strain was identified as K. palustris based upon analyses of cellular chemical compositions (cellular fatty acids, isoprenoides, quinones, and sugars), patterns of carbon source, average nucleotide identity of genome and digital DNA-DNA relatedness. Six genes coding to enzymes or proteins for arsenate reduction and arsenite-bumping were detected in the genome, demonstrating that this strain is resistant to As possibly by reducing As5+ to As3+, and then bumping As3+ out of the cell. However, this estimation was not confirmed since no arsenate reduction was detected in a subsequent assay. This study reported for the first time the presence of phylogenetically distinct arsenate reductase genes in a Kocuria strain and evidenced the possible horizontal transfer of these genes among the endophytic bacteria.


Assuntos
Arseniato Redutases/genética , Arseniatos/metabolismo , Micrococcaceae/enzimologia , Micrococcaceae/genética , Arsênico/farmacologia , Arsenitos/metabolismo , Testes de Sensibilidade Microbiana , Micrococcaceae/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Traqueófitas/microbiologia
5.
J Biochem Mol Toxicol ; 33(9): e22368, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332900

RESUMO

Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms. Apparently, BBR and MET recruit both direct (as an antioxidant) and indirect mechanisms (Sirt3 content) to deal with arsenic trioxide toxicity. Metformin compared with BBR exhibited a less significant effect on ROS levels and since its direct antioxidant property is minor, depressed the ROS level mainly through the Sirt3 modification.


Assuntos
Arsênico/farmacologia , Berberina/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Sirtuínas/metabolismo , Animais , Mitocôndrias/metabolismo , Ratos
6.
Oncol Rep ; 42(3): 1005-1016, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322264

RESUMO

According to a report of the International Agency for Research on Cancer, arsenic and inorganic arsenic compounds are classified into Group 1 carcinogens with regard to human health. Epidemiological studies indicate that arsenic is one of the main risk factors for the development of bladder cancer. In the present study, arsenic­altered gene expression in mouse bladder tissues and in human urothelial cells was compared. In the mouse model, sodium arsenite­induced mouse urothelial hyperplasia and intracellular inclusions were present. Following DNA array analysis, four genes with differential expression were selected for quantitative real­time PCR assay. The genes were the following: Cystathionine ß­synthase (CBS), adenosine A1 receptor (ADORA1), metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) and Wnt inhibitory factor 1 (Wif1). The results indicated a significant increase in the levels of Cbs and Adora1. The analysis of the DNA CpG methylation levels of the mouse Cbs and Adora1 genes revealed no significant change. In contrast to these observations, the four genes were further analyzed in the human normal urothelial cell line SV­HUC1. The data indicated that WIF1 gene expression was decreased by sodium arsenite, whereas this was not noted for CBS, MALAT1 and ADORA1. Sodium arsenite decreased mRNA and protein expression levels of the WIF1 gene. In addition, the methylation levels of the WIF1 gene were increased. Sodium arsenite inhibited cell proliferation and promoted cell migration as demonstrated in cell functional assays. The gene status was compared in 8 human urothelial cell lines, and WIF1 mRNA expression levels were determined to be higher, whereas DNA CpG methylation levels were lower in SV­HUC1 cells compared with those noted in the other 7 bladder cancer cell lines. In summary, the data indicated that sodium arsenite decreased WIF1 gene expression and promoted cell migration. The increased methylation levels of WIF1 DNA CpG could be a potential biomarker for bladder cancer.


Assuntos
Arsênico/farmacologia , Biomarcadores Tumorais/metabolismo , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Urotélio/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Humanos , Metionina Sulfóxido Redutases/genética , Metionina Sulfóxido Redutases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptor A2A de Adenosina/genética , Receptor A2A de Adenosina/metabolismo , Células Tumorais Cultivadas , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/efeitos dos fármacos , Urotélio/metabolismo
7.
Environ Sci Pollut Res Int ; 26(17): 17438-17449, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31020532

RESUMO

Soil textural composition may be important to control arsenic (As) behavior in soil and movement to plant. Two independent parallel experiments comprising of five As levels (0, 50, 100, 150, and 200 mg As kg-1 soil) and three soil textural types (sandy, loamy, and clayey) were designed for determining As fractionation in soils and its consequential effects on growth, yield, and physiological characteristics of sunflower (Helianthus annuus L.). Six As fractions, i.e., NH4Cl-extractable, NH4F-extractable, NaOH-extractable, H2SO4-extractable, H2O2-extractable, and HNO3-extractable, were determined. On an average, NH4Cl-extractable As (the most phytoavailable among the extracted fractions) was 48.9, 19.8, and 6.6% of the total As while the bioaccumulation factor for root ranged between 1.9 and 9.5, 1.8 and 4.4, and 0.8 and 2.1 for sandy, loamy, and clayey textured soils, respectively. There was an increase of 8.3, 5.6, and 6.0 times in malondialdehyde with a subsequent reduction in photosynthetic rate by 53.3, 42.7, and 38.0% and achene yield 90.0, 87.1, and 85.5% in sandy, loamy, and clayey textured soils, respectively at 200 mg As kg-1 as compared with the control. Antioxidant enzyme activities were increased with increasing As addition, and maximum activities were found at 150 mg As kg-1, where catalase activities were 377.7, 341.6, and 292.0%; peroxidase 788.5, 758.6, and 737.0%; and superoxide dismutase 235.7, 191.8, and 177.2% higher in sandy, loamy, and clayey textured soils, respectively as compared with the control. In conclusion, As fractionation was markedly influenced by soil texture, and toxic effects of As on growth, yield and physiological characteristics of sunflower were maximum in sandy followed by loamy and clayey textured soils in descending order.


Assuntos
Arsênico/química , Helianthus/crescimento & desenvolvimento , Peróxido de Hidrogênio/química , Solo/química , Arsênico/farmacologia , Peróxido de Hidrogênio/farmacologia
8.
J Vis Exp ; (144)2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30855562

RESUMO

Understanding the physiologic mechanisms of wound healing has been the focus of ongoing research for many years. This research directly translates into changes in clinical standards used for treating wounds and decreasing morbidity and mortality for patients. Wound healing is a complex process that requires strategic cell and tissue interaction and function. One of the many critically important functions of wound healing is individual and collective cellular migration. Upon injury, various cells from the blood, surrounding connective, and epithelial tissues rapidly migrate to the wound site by way of chemical and/or physical stimuli. This migration response can largely dictate the outcomes and success of a healing wound. Understanding this specific cellular function is important for translational medicine that can lead to improved wound healing outcomes. Here, we describe a protocol used to better understand cellular migration as it pertains to wound healing, and how changes to the cellular environment can significantly alter this process. In this example study, dermal fibroblasts were grown in media supplemented with fetal bovine serum (FBS) as monolayer cultures in tissue culture flasks. Cells were aseptically transferred into tissue culture treated 12-well plates and grown to 100% confluence. Upon reaching confluence, the cells in the monolayer were vertically scratched using a p200 pipet tip. Arsenic diluted in culture media supplemented with FBS was added to individual wells at environmentally relevant doses ranging 0.1-10 M. Images were captured every 4 hours (h) over a 24 h period using an inverted light microscope to observe cellular migration (wound closure). Images were individually analyzed using image analysis software, and percent wound closure was calculated. Results demonstrate that arsenic slows down wound healing. This technique provides a rapid and inexpensive first screen for evaluation of the effects of contaminants on wound healing.


Assuntos
Arsênico/farmacologia , Movimento Celular/efeitos dos fármacos , Técnicas Citológicas , Pele/citologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
9.
Int J Mol Sci ; 20(4)2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813460

RESUMO

Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS2O3) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.


Assuntos
Carcinogênese/genética , Proteínas do Tecido Nervoso/metabolismo , Oncogenes , Regulação para Cima/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Arsênico/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Proteína Proto-Oncogênica N-Myc/metabolismo , Invasividade Neoplásica , Proteínas do Tecido Nervoso/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Dalton Trans ; 48(16): 5183-5192, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30838370

RESUMO

Cleavage of the bromide bridges in [Pd2(µ-Br)2{κ2(Sn,As)-2-MeBrSnC6F4AsPh2}2] (1) by diphosphine ligands gave the mono- and dinuclear palladacycles [Pd(L)Br{κ2(Sn,As)-2-MeBrSnC6F4AsPh2}] [L = dppe (2) dppm (3), ortho-dppBz (4)] and [Pd2Br2(para-dppBz){κ2(Sn,As)-2-MeBrSnC6F4AsPh2}2] (5). The interactions of these complexes with DNA (CT-DNA) and proteins (human serum albumin) were studied by UV-Vis and fluorescence spectroscopy, respectively. The results confirmed the interaction of these palladium complexes with CT-DNA through groove binding, and their strong binding affinity to HSA. The anti-proliferative activities of complexes 1-5 were tested against four human cancer cell lines (HeLa, A549, PC-3, and HT1080) and normal keratinocytes (HaCaT). Among the series, the palladium(ii) complex containing the 1,2-bis(diphenylphosphino)benzene ligand (4) showed the highest cytotoxicity against HeLa, PC-3 and HT1080 cells, with IC50 values of 0.25 ± 0.08, 0.85 ± 0.11, and 0.66 ± 0.15 µM, respectively. Interestingly, compound 4 exhibited lower cytotoxic activity toward normal HaCaT cells (IC50 = 4.65 ± 0.16 µM). Additionally, this complex exhibited lower toxicity and better anti-cancer activity than cisplatin. Further mechanistic studies, including Hoechst staining and flow cytometry, confirmed that complex 4 induced G2/M phase cell cycle arrest and apoptotic cell death in HeLa cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Arsênico/química , Arsênico/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quelantes/síntese química , Quelantes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Estrutura Molecular , Paládio/química , Paládio/farmacologia , Fosfinas/química , Fosfinas/farmacologia , Relação Estrutura-Atividade , Estanho/química , Estanho/farmacologia
11.
Plant Physiol Biochem ; 138: 26-35, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30831360

RESUMO

Inoculation practice with plant growth-promoting bacteria (PGPB) has been proposed as a good biotechnological tool to enhance plant performance and alleviate heavy metal/metalloid stress. Soybean is often cultivated in soil with high arsenic (As) content or irrigated with As-contaminated groundwater, which causes deleterious effects on its growth and yield, even when it was inoculated with rhizobium. Thus, the effect of double inoculation with known PGPB strains, Bradyrhizobium japonicum E109 and Azospirillum brasilense Az39 was evaluated in plants grown in pots under controlled conditions and treated with As. First, the viability of these co-cultivated bacteria was assayed using a flow cytometry analysis using SYTO9 and propidium iodide (PI) dyes. This was performed in vitro to evaluate the bacterial population dynamic under 25 µM AsV and AsIII treatment. A synergistic effect was observed when bacteria were co-cultured, since mortality diminished, compared to each growing alone. Indole acetic acid (IAA) produced by A. brasilense Az39 would be one of the main components involved in B. japonicum E109 mortality reduction, mainly under AsIII treatment. Regarding in vivo assays, under As stress, plant growth improvement, nodule number and N content increase were observed in double inoculated plants. Furthermore, double inoculation strategy reduced As translocation to aerial parts thus improving As phytostabilization potential of soybean plants. These results suggest that double inoculation with B. japonicum E109 and A. brasilense Az39 could be a safe and advantageous practice to improve growth and yield of soybean exposed to As, accompanied by an important metalloid phytostabilization.


Assuntos
Arsênico/farmacologia , Azospirillum brasilense/metabolismo , Bradyrhizobium/metabolismo , Soja/crescimento & desenvolvimento , Soja/microbiologia , Estresse Fisiológico/efeitos dos fármacos
12.
Microb Ecol ; 78(3): 589-602, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30725170

RESUMO

Arsenic (As) and antimony (Sb) are both toxic metalloids that are of primary concern for human health. Mining activity has introduced elevated levels of arsenic and antimony into the rivers and has increased the risks of drinking water contamination in China. Due to their mobility, the majority of the metalloids originating from mining activities are deposited in the river sediments. Thus, depending on various geochemical conditions, sediment could either be a sink or source for As and Sb in the water column. Microbes are key mediators for biogeochemical transformation and can both mobilize or precipitate As and Sb. To further understand the microbial community responses to As and Sb contamination, sediment samples with different contamination levels were collected from three rivers. The result of the study suggested that the major portions of As and Sb were in strong association with the sediment matrix and considered nonbioavailable. These fractions, however, were also suggested to have profound influences on the microbial community composition. As and Sb contamination caused strong reductions in microbial diversity in the heavily contaminated river sediments. Microorganisms were more sensitive to As comparing to Sb, as revealed by the co-occurrence network and random forest predictions. Operational taxonomic units (OTUs) that were potentially involved in As and Sb metabolism, such as Anaerolinea, Sphingomonas, and Opitutus, were enriched in the heavily contaminated samples. In contrast, many keystone taxa, including members of the Hyphomicrobiaceae and Bradyrhizobiaceae families, were inhibited by metalloid contamination, which could further impair crucial environmental services provided by these members.


Assuntos
Antimônio/análise , Arsênico/análise , Bactérias/isolamento & purificação , Sedimentos Geológicos/microbiologia , Microbiota , Rios/microbiologia , Poluentes Químicos da Água/análise , Antimônio/farmacologia , Arsênico/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , China , Sedimentos Geológicos/análise , Rios/química , Poluentes Químicos da Água/farmacologia , Poluição da Água/análise
13.
PLoS One ; 14(2): e0210737, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30721235

RESUMO

The arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resistance against chemotherapy to the parasite, leading to modulation in the host's immune response. This hypothesis appears to be consistent with the in vitro findings that in arsenic-exposed parasites, the mitochondrial membrane potential became depolarized, whereas the reduced thiol and lactate production was overexpressed with enhanced glucose consumption; therefore, the reduced thiol possibly supports an immunosuppressive state in the host cells. This observation was well supported by the down-regulated expression of pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) with a suppressed anti-leishmanial function of macrophage (NO, ROS). In contrast, the pathophysiological mechanism of VL has received ample support by the promotion of Th2 cytokines (IL-4 and IL-10) in the presence of arsenic-exposed Leishmania parasites (LdAS). Dysfunction of mitochondria and the overexpression of lactate production raise the possibility of the Warburg effect being operative through the up-regulation of glucose consumption by parasites to enhance the energy production, possibly augmenting virulence. Therefore, we surmise from our data that arsenic exposure to Leishmania donovani modulates the immune response and infection pattern by impairing parasite function, which may affect the anti-leishmanial effect in VL.


Assuntos
Arsênico/farmacologia , Leishmania donovani/imunologia , Leishmaniose Visceral , Macrófagos Peritoneais , Animais , Citocinas/imunologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/parasitologia , Macrófagos Peritoneais/patologia , Camundongos , Óxido Nítrico/imunologia , Espécies Reativas de Oxigênio/imunologia
14.
Clin Exp Dermatol ; 44(5): 512-519, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30456849

RESUMO

BACKGROUND: Ultraviolet (UV)B radiation has long been considered a carcinogen in both epidemiological surveys and experimental studies. However, recent work has suggested that different dosages of UVB exert different influences on cells. There are also co-carcinogenesis factors such as arsenic that affect the role of UVB. AIM: To explore the co-carcinogenesis effect of UVB and arsenic on the mouse epidermal cell line JB6 and the mechanism underlying it. METHODS: Growth of JB6 cells was measured by MTT assay. We carried out a comet assay to determine the DNA damage caused by UVB and arsenic, and tested the expression of DNA repair protein by western blotting. Reactive oxygen species (ROS) were measured using DCF and DHE staining, and changes in antioxidant enzymes were assessed using western blotting. RESULTS: Viability assays showed that arsenic increased the UVB-induced death rate. Arsenic enhanced DNA damage caused by UVB both directly by injury to double-stranded DNA and indirectly by reducing the capability of DNA repair in JB6 cells. All of these effects are the results of increased ROS generation and reduced expression of the antioxidant enzyme superoxide dismutase (SOD)1. CONCLUSION: Arsenic was found to enhance UVB-induced production of ROS and to downregulate SOD1 expression, leading to DNA damage and apoptosis in mouse skin cells. The combination of arsenic and UVB exposure was found to differentially regulate the expression of SOD1 and SOD2.


Assuntos
Apoptose/efeitos dos fármacos , Arsênico/farmacologia , Dano ao DNA/efeitos dos fármacos , Células Epidérmicas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Apoptose/efeitos da radiação , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Células Epidérmicas/metabolismo , Células Epidérmicas/efeitos da radiação , Camundongos , Espécies Reativas de Oxigênio/efeitos da radiação , Superóxido Dismutase-1/efeitos dos fármacos , Superóxido Dismutase-1/metabolismo
15.
Appl Biochem Biotechnol ; 187(1): 365-377, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29951962

RESUMO

Arsenic is one of the most widespread global environmental toxicants associated with endemic poisoning. ATP-binding cassette (ABC) proteins are transmembrane channels that transport and dispose of lipids and metabolic products across the plasma membrane. The majority of ABC family members (including ABCB1 and ABCC1) are reported to play a role in the development of arsenic and drug resistance in mammals. Previously, we established a human arsenic-resistant ECV-304 (AsRE) cell line and identified ABCA1 as a novel arsenic resistance gene. In the current study, we further investigated the potential contribution of ABCA1, ABCB1, and ABCC1 to arsenic resistance through measurement of survival rates and arsenic accumulation in AsRE cells with RNA interference. The arsenic resistance capacity of ABCC1 was the strongest among the three genes, while those of ABCA1 and ABCB1 were similar. Double or triple gene knockdown of ABCA1, ABCB1, and ABCC1 via RNA interference led to a decrease significant in arsenic resistance when ABCA1/ABCB1 or ABCB1/ABCC1 were simultaneously silenced. Interestingly, no differences were evident between cells with ABCA1/ABCC1 and ABCC1 only knockdown. Our findings suggest that ABCA1 and ABCB1 proteins display similar arsenic resistance capabilities and possibly coordinate to promote arsenic resistance in AsRE cells.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/fisiologia , Arsênico/farmacologia , Resistência a Medicamentos/genética , Transportador 1 de Cassete de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/fisiologia , Arsênico/metabolismo , Transporte Biológico , Linhagem Celular , Técnicas de Silenciamento de Genes , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Interferência de RNA
16.
Am J Physiol Endocrinol Metab ; 316(3): E464-E474, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30562058

RESUMO

In arsenic-endemic regions of the world, arsenic exposure correlates with diabetes mellitus. Multiple animal models of inorganic arsenic (iAs, as As3+) exposure have revealed that iAs-induced glucose intolerance manifests as a result of pancreatic ß-cell dysfunction. To define the mechanisms responsible for this ß-cell defect, the MIN6-K8 mouse ß-cell line was exposed to environmentally relevant doses of iAs. Exposure to 0.1-1 µM iAs for 3 days significantly decreased glucose-induced insulin secretion (GIIS). Serotonin and its precursor, 5-hydroxytryptophan (5-HTP), were both decreased. Supplementation with 5-HTP, which loads the system with bioavailable 5-HTP and serotonin, rescued GIIS, suggesting that recovery of this pathway was sufficient to restore function. Exposure to iAs was accompanied by an increase in mRNA expression of UDP-glucuronosyltransferase 1 family, polypeptide a6a (Ugt1a6a), a phase-II detoxification enzyme that facilitates the disposal of cyclic amines, including serotonin, via glucuronidation. Elevated Ugt1a6a and UGT1A6 expression levels were observed in mouse and human islets, respectively, following 3 days of iAs exposure. Consistent with this finding, the enzymatic rate of serotonin glucuronidation was increased in iAs-exposed cells. Knockdown by siRNA of Ugt1a6a during iAs exposure restored GIIS in MIN6-K8 cells. This effect was prevented by blockade of serotonin biosynthesis, suggesting that the observed iAs-induced increase in Ugt1a6a affects GIIS by targeting serotonin or serotonin-related metabolites. Although it is not yet clear exactly which element(s) of the serotonin pathway is/are most responsible for iAs-induced GIIS dysfunction, this study provides evidence that UGT1A6A, acting on the serotonin pathway, regulates GIIS under both normal and pathological conditions.


Assuntos
5-Hidroxitriptofano/efeitos dos fármacos , Arsênico/farmacologia , Diabetes Mellitus/metabolismo , Glucuronosiltransferase/efeitos dos fármacos , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Serotonina/metabolismo , 5-Hidroxitriptofano/metabolismo , Adulto , Animais , Linhagem Celular , Feminino , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Mitocôndrias , Consumo de Oxigênio , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo
17.
PLoS One ; 13(12): e0209014, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543710

RESUMO

Three arsenic species in urine are measured using an atomic absorption spectrophotometer. RT-PCR is performed to detect the expression levels of AS3MT, 3 miRNAs, and 17 relative mRNAs in 43 workers producing arsenic trioxide, 36 workers who stopped exposure to arsenic for 85 days, and 24 individuals as the control group. The concentrations of urinary arsenic are very high in workers. A negative correlation between AS3MT and MiR-548c-3p is found. There exist significant changes for most selected miRNAs and mRNAs in workers. There are no significant differences between workers who stopped exposure to arsenic and the control group for most miRNAs and mRNAs, but the MiR-548c-3p levels show significant changes. Similar positive correlations between the expression of AS3MT and all selected mRNAs are found. Negative correlations between the expression of MiR-548c-3p and many relative mRNAs are found as well. AS3MT and MiR-548c-3p may regulate arsenic methylation jointly, which when involved in a group of relative mRNAs may play roles in arsenic metabolism and epigenetic changes caused by this metabolism.


Assuntos
Arsênico/química , Arsênico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Metiltransferases/genética , MicroRNAs/genética , Adulto , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Masculino , Metilação , RNA Mensageiro/genética
18.
World J Microbiol Biotechnol ; 34(12): 177, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30446973

RESUMO

Bioremediation of arsenic (As) pollution is an important environmental issue. The present investigation was carried out to isolate As-resistant novel bacteria and characterize their As transformation and tolerance ability. A total of 170 As-resistant bacteria were isolated from As-contaminated soils at the Kangjiawan lead-zinc tailing mine, located in Hunan Province, southern China. Thirteen As-resistant isolates were screened by exposure to 260 mM Na2HAsO4·7H2O, most of which showed a very high level of resistance to As5+ (MIC ≥ 600 mM) and As3+ (MIC ≥ 10 mM). Sequence analysis of 16S rRNA genes indicated that the 13 isolates tested belong to the phyla Firmicutes, Proteobacteria and Actinobacteria, and these isolates were assigned to eight genera, Bacillus, Williamsia, Citricoccus, Rhodococcus, Arthrobacter, Ochrobactrum, Pseudomonas and Sphingomonas. Genes involved in As resistance were present in 11 of the isolates. All 13 strains transformed As (1 mM); the oxidation and reduction rates were 5-30% and 10-51.2% within 72 h, respectively. The rates of oxidation by Bacillus sp. Tw1 and Pseudomonas spp. Tw224 peaked at 42.48 and 34.94% at 120 h, respectively. For Pseudomonas spp. Tw224 and Bacillus sp. Tw133, the highest reduction rates were 52.01% at 48 h and 48.66% at 144 h, respectively. Our findings will facilitate further research into As metabolism and bioremediation of As pollution by genome sequencing and genes modification.


Assuntos
Arsênico/metabolismo , Bactérias Aeróbias/classificação , Bactérias Aeróbias/isolamento & purificação , Bactérias Aeróbias/metabolismo , Tolerância a Medicamentos , Filogenia , Zinco/metabolismo , Arseniatos/metabolismo , Arsênico/farmacologia , Arsenitos/metabolismo , Bactérias Aeróbias/genética , Biodegradação Ambiental , China , Farmacorresistência Bacteriana , Genes Bacterianos/genética , Metais Pesados/metabolismo , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Análise de Sequência , Microbiologia do Solo , Poluentes do Solo/metabolismo
19.
Appl Environ Microbiol ; 84(24)2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30315082

RESUMO

Arsenic-resistant bacteria have evolved various efflux systems for arsenic resistance. Five arsenic efflux proteins, ArsB, Acr3, ArsP, ArsJ, and MSF1, have been reported. In this study, comprehensive analyses were performed to study the function of a putative major facilitator superfamily gene, arsK, and the regulation of arsK transcriptional expression in Agrobacterium tumefaciens GW4. We found that (i) arsK is located on an arsenic gene island in strain GW4. ArsK orthologs are widely distributed in arsenic-resistant bacteria and are phylogenetically divergent from the five reported arsenic efflux proteins, indicating that it may be a novel arsenic efflux transporter. (ii) Reporter gene assays showed that the expression of arsK was induced by arsenite [As(III)], antimonite [Sb(III)], trivalent roxarsone [Rox(III)], methylarsenite [MAs(III)], and arsenate [As(V)]. (iii) Heterologous expression of ArsK in an arsenic-hypersensitive Escherichia coli strain showed that ArsK was essential for resistance to As(III), Sb(III), Rox(III), and MAs(III) but not to As(V), dimethylarsenite [dimethyl-As(III)], or Cd(II). (iv) ArsK reduced the cellular accumulation of As(III), Sb(III), Rox(III), and MAs(III) but not to As(V) or dimethyl-As(III). (v) A putative arsenic regulator gene arsR2 was cotranscribed with arsK, and (vi) ArsR2 interacted with the arsR2-arsK promoter region without metalloids and was derepressed by As(III), Sb(III), Rox(III), and MAs(III), indicating the repression activity of ArsR2 for the transcription of arsK These results demonstrate that ArsK is a novel arsenic efflux protein for As(III), Sb(III), Rox(III), and MAs(III) and is regulated by ArsR2. Bacteria use the arsR2-arsK operon for resistance to several trivalent arsenicals or antimonials.IMPORTANCE The metalloid extrusion systems are very important bacterial resistance mechanisms. Each of the previously reported ArsB, Acr3, ArsP, ArsJ, and MSF1 transport proteins conferred only inorganic or organic arsenic/antimony resistance. In contrast, ArsK confers resistance to several inorganic and organic trivalent arsenicals and antimonials. The identification of the novel efflux transporter ArsK enriches our understanding of bacterial resistance to trivalent arsenite [As(III)], antimonite [Sb(III)], trivalent roxarsone [Rox(III)], and methylarsenite [MAs(III)].


Assuntos
Agrobacterium tumefaciens/efeitos dos fármacos , Antimônio/farmacologia , Arsenitos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Roxarsona/farmacologia , Agrobacterium tumefaciens/genética , Sequência de Aminoácidos , Arseniatos/farmacologia , Arsênico/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/fisiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Genes Bacterianos/genética , Ilhas Genômicas , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Óperon
20.
World J Microbiol Biotechnol ; 34(10): 156, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30284648

RESUMO

Microorganisms associated with plants have a great biotechnological potential, but investigations of these microorganisms associated with native plants in peculiar environments has been incipient. The objective of this study was to analyze the plant growth-promoting bacteria potential of cultivable bacteria associated with rare plants from the ferruginous rocky fields of the Brazilian Iron Quadrangle. The roots and rhizospheres of nine endemic plants species and samples of a root found in a lateritiric duricrust (canga) cave were collected, the culturable bacteria isolated and prospected for distinct biotechnological and ecological potentials. Out of the 148 isolates obtained, 8 (5.4%) showed potential to promote plant growth, whereas 4 (2.7%) isolates acted as biocontrol agents against Xanthomonas citri pathotype A (Xac306), reducing the cancrotic lesions by more than 60% when co-inoculated with this phytopathogen in Citrus sinensis plants. Moreover, other 4 (2.7%) isolates were classified as potential bioremediation agents, being able to withstand high concentrations of arsenite (5 mM As3+) and arsenate (800 mM As5+), by removing up to 35% and 15% of this metalloid in solution, respectively. These same four isolates had a positive influence on the growth of both the roots and the aerial parts when inoculated with tomato seeds in the soil contaminated with arsenic. This is the first time that an investigation highlights the potentialities of bacteria associated with rare plants of ferruginous rocky fields as a reservoir of microbiota of biotechnological and ecological interest, highlighting the importance of conservation of this area that is undergoing intense anthropic activity.


Assuntos
Bactérias/metabolismo , Fenômenos Fisiológicos Bacterianos , Biotecnologia , Desenvolvimento Vegetal/fisiologia , Raízes de Plantas/microbiologia , Rizosfera , Amilases/metabolismo , Arseniatos/metabolismo , Arsênico/metabolismo , Arsênico/farmacologia , Arsenitos/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Biodegradação Ambiental , Biodiversidade , Agentes de Controle Biológico , Brasil , Resistência a Medicamentos , Fertilizantes , Cianeto de Hidrogênio/metabolismo , Ácidos Indolacéticos/metabolismo , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/microbiologia , Microbiota/fisiologia , Fixação de Nitrogênio , Peptídeo Hidrolases/metabolismo , Fosfatos/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Patologia Vegetal , Raízes de Plantas/química , RNA Ribossômico 16S/genética , Sideróforos/metabolismo , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Xanthomonas/fisiologia
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