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1.
Chemosphere ; 257: 127264, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32516671

RESUMO

Degradation of phenol by sodium persulfate (SPS) in hot compressed water (HCW) was investigated in a lab-built fused quartz tube reactor (FQTR) coupled with Raman spectroscopy system. The species of S2O82-, SO42-, HSO4-, SO32- and HSO3- in the reaction system were qualitatively and quantitatively analyzed by Raman spectroscopy. The hydrothermal stability of phenol and SPS at different temperature and the degradation of phenol by SPS were also studied. The results indicated that phenol was not stable in aqueous solution above 200 °C, and that only SO42- was generated in the hydrolysis of SPS at temperatures below 50 °C, and SO42- and HSO4- were generated at higher temperatures. The maximum conversion rate (90.93%) and mineralization efficiency (38.88%) of phenol by SPS was obtained at reaction temperature of 300 °C with 180 min reaction time. During the degradation of phenol by SPS, HSO4- was the main product and S∗ (not detected by Raman spectroscopy) exhibits a positive correlation with temperature. In addition, a degradation pathway of phenol by SPS was proposed. The degradation data for the kinetic analysis indicated that the reaction followed pseudo first-order kinetics, and the reaction rate constants (ks) were given as k50 °C = 0.0083 min-1, k100°C = 0.0197 min-1, k200 °C = 0.0498 min-1, k300 °C = 0.0619 min-1 and k400°C = 0.0505 min-1 at 30 min reaction. Moreover, the activation energy (12.580 kJ mol-1), the enthalpy change (9.064 kJ mol-1) and the entropy change (-222.104 J mol-1) of the reaction were also calculated.


Assuntos
Fenol/metabolismo , Compostos de Sódio/toxicidade , Sulfatos/toxicidade , Poluentes Químicos da Água/toxicidade , Temperatura Alta , Cinética , Oxirredução , Fenol/química , Compostos de Sódio/metabolismo , Análise Espectral Raman , Sulfatos/metabolismo , Temperatura , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos
2.
Ecotoxicol Environ Saf ; 201: 110802, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531573

RESUMO

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (-1743, -1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (ß-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced ß-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin.


Assuntos
Arsenitos/toxicidade , Metilação de DNA/efeitos dos fármacos , Transportador de Glucose Tipo 2/genética , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Compostos de Sódio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Epigênese Genética/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Técnicas In Vitro , Insulina/genética , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Regiões Promotoras Genéticas , Ratos , Ratos Wistar , Transativadores/genética
3.
Toxicol Appl Pharmacol ; 394: 114959, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32201329

RESUMO

Arsenic is a ubiquitous environmental toxicant, found in high concentrations worldwide. Although abundant research has dealt with arsenic-induced cancers, studies on mechanisms of non-malignant lung diseases have not been complete. In addition, decades of research have mostly concentrated on high-dose arsenic exposure, which has very limited use in modeling the biological effects of today's low-dose exposures. Indeed, accumulated evidence has shown that low-dose arsenic exposure (i.e. ≤100 ppb) may also alter lung homeostasis by causing host susceptibility to viral infection. However, the underlying mechanism of this alteration is unknown. In this study, we found that low-dose sodium arsenite (As (III)) repressed major airway mucins-MUC5AC and MUC5B at both mRNA and protein levels. We further demonstrated that this repression was not caused by cellular toxicity or mediated by the reduction of a common mucin-inducing pathway-EGFR. Other established mucin activators- dsRNA, IL1ß or IL17 were not able to override As (III)-induced mucin repression. Interestingly, the suppressing effect of As (III) appeared to be partially reversible, and supplementation of all trans retinoic acid (t-RA) doses dependently restored mucin gene expression. Further analyses indicated that As (III) treatment significantly reduced the protein level of retinoic acid receptors (RARα, γ and RXRα) as well as RARE promoter reporter activity. Therefore, our study fills in an important knowledge gap in the field of low-dose arsenic exposure. The interference of RA signaling, and mucin gene expression may be important pathogenic factors in low-dose arsenic induced lung toxicity.


Assuntos
Arsênico/toxicidade , Mucinas/biossíntese , Mucosa Respiratória/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tretinoína , Arsenitos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mucina-5AC/antagonistas & inibidores , Mucina-5AC/genética , Mucina-5B/antagonistas & inibidores , Mucina-5B/genética , Mucosa Respiratória/efeitos dos fármacos , Compostos de Sódio/toxicidade
4.
Toxicol Appl Pharmacol ; 393: 114955, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32171569

RESUMO

Inorganic arsenic is among the major contaminants of groundwater in the world. Worldwide population-based studies demonstrate that chronic arsenic exposure is associated with poor cognitive performance among children and adults, while research in animal models confirms learning and memory deficits after arsenic exposure. The aim of this study was to investigate the long-term effects of environmentally relevant arsenic exposure in the myelination process of the prefrontal cortex (PFC) and corpus callosum (CC). A longitudinal study with repeated follow-up assessments was performed in male Wistar rats exposed to 3 ppm sodium arsenite in drinking water. Animals received the treatment from gestation until 2, 4, 6, or 12 months of postnatal age. The levels of myelin basic protein (MBP) were evaluated by immunohistochemistry/histology and immunoblotting from the PFC and CC. As plausible alterations associated with demyelination, we considered mitochondrial mass (VDAC) and two axonal damage markers: amyloid precursor protein (APP) level and phosphorylated neurofilaments. To analyze the microstructure of the CC in vivo, we acquired diffusion-weighted images at the same ages, from which we derived metrics using the tensor model. Significantly decreased levels of MBP were found in both regions together with significant increases of mitochondrial mass and slight axonal damage at 12 months in the PFC. Ultrastructural imaging demonstrated arsenic-associated decreases of white matter volume, water diffusion anisotropy, and increases in radial diffusivity. This study indicates that arsenic exposure is associated with a significant and persistent negative impact on microstructural features of white matter tracts.


Assuntos
Intoxicação por Arsênico/patologia , Doenças Desmielinizantes/patologia , Envelhecimento , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Intoxicação por Arsênico/diagnóstico por imagem , Arsenitos/toxicidade , Axônios/patologia , Corpo Caloso/patologia , Doenças Desmielinizantes/diagnóstico por imagem , Imagem de Tensor de Difusão , Água Potável , Imuno-Histoquímica , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína Básica da Mielina/metabolismo , Proteínas de Neurofilamentos/metabolismo , Córtex Pré-Frontal/patologia , Ratos , Ratos Wistar , Compostos de Sódio/toxicidade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
5.
Toxicology ; 437: 152440, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32197950

RESUMO

Arsenic is an endocrine disruptor that promotes breast cancer (BCa) development. Estrogen synthesis, through aromatase activation, is essential for BCa promotion and progression through activating the G-coupled estrogen receptor 1 (GPER1), regulating rapid nongenomic effects involved in cell proliferation and migration of BCa cells. Herein, was studied the role of aromatase activation and the GPER1 pathway on sodium arsenite-induced promotion and progression of MDA-MB-231 and MDA-MB-453 BCa cell lines. Our results demonstrated that 0.1 µM of sodium arsenite induces cell proliferation, migration, invasion, and stimulates aromatase activity of BCa cell lines MDA-MB-231, MDA-MB-453, MCF-7, but not in a nontumorigenic breast epithelial cell line (MCF-12A). Using letrozole (an aromatase inhibitor) and G-15 (a GPER1-selective antagonist), we demonstrated that sodium arsenite-induced proliferation and migration is mediated by induction of aromatase enzyme and, at least in part, by GPER1 activation in MDA-MB-231 and MDA-MB-453 cells. Sodium arsenite induced phosphorylation of Src that participated in sodium arsenite-induced aromatase activity, and -cell proliferation of MDA-MB-231 cell line. Overall, data suggests that sodium arsenite induces a positive-feedback loop, resulting in the promotion and progression of BCa cells, through induction of aromatase activity, E2 production, GPER1 stimulation, and Src activation.


Assuntos
Aromatase/metabolismo , Arsenitos/toxicidade , Neoplasias da Mama/enzimologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ativadores de Enzimas/toxicidade , Compostos de Sódio/toxicidade , Neoplasias da Mama/patologia , Ativação Enzimática , Estradiol/metabolismo , Feminino , Humanos , Células MCF-7 , Invasividade Neoplásica , Fosforilação , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Quinases da Família src/metabolismo
6.
Toxicol Appl Pharmacol ; 391: 114912, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32014540

RESUMO

Arsenic, an environmental contaminant in drinking water worldwide is well-established to increase cardiovascular diseases (CVDs) in humans. Of these, thrombotic events represent a major adverse effect associated with arsenic exposure, for which an abundance of epidemiological evidence exists. Platelet aggregation constitutes a pivotal step in thrombosis but arsenic alone doesn't induce aggregation and the mechanism underlying arsenic-induced thrombosis still remains unclear. Here we demonstrated that arsenic induces morphological changes of platelets, i.e., contraction and pseudopod projection, the primal events of platelet activation, which can increase platelet reactivity. Arsenite induced prominent platelet shape changes in a dose-dependent manner in freshly isolated human platelets. Of note, arsenite suppressed focal adhesion kinase (FAK) activity, which in turn activated RhoA, leading to altered actin assembly through LIMK activation, and subsequent cofilin inactivation. Arsenic-induced platelet shape change appeared to increase the sensitivity to thrombin and ADP-induced aggregation. Supporting this, latrunculin A, an inhibitor of actin-dynamics abolished it. Taken together, we demonstrated that arsenic induces cytoskeletal changes and shape changes of platelets through FAK-mediated alteration of actin dynamics, which renders platelets reactive to activating stimuli, ultimately contributing to increased thrombosis.


Assuntos
Actinas/metabolismo , Arsenitos/toxicidade , Plaquetas/patologia , Plaquetas/ultraestrutura , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Compostos de Sódio/toxicidade , Difosfato de Adenosina/farmacologia , Adolescente , Adulto , Humanos , Técnicas In Vitro , Quinases Lim/antagonistas & inibidores , Masculino , Selectina-P/biossíntese , Agregação Plaquetária/efeitos dos fármacos , Adulto Jovem , Proteína rhoA de Ligação ao GTP
7.
Toxicology ; 435: 152409, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32068019

RESUMO

Arsenic is a known human carcinogen. Early-life exposure to inorganic arsenic induces tumors in humans and in C3H mice. We hypothesized that arsenic exposure in utero may induce epigenetic changes at the level of DNA methylation and miRNA alterations that could lead to greater postnatal susceptibility to cancer. To test this hypothesis, pregnant C3H mice were given sodium arsenite at doses known to cause liver cancer (42.5 and 85 ppm in the drinking water) from gestation day 8-19, and the livers from male fetal mice were collected for analysis. The antibody against 5-methylcytosine was used to perform chromatin-immunoprecipitation coupled with sequencing (ChIP-Seq) to determine genome-wide methylation alterations. In utero arsenic exposure produced global DNA hypomethylation and an array of gene-specific DNA methylation changes, including hypomethylation of Cyclin D1 and hypermethylation of Tp53. Illumina Correlation Engine analysis revealed 260 methylation alterations that would affect 143 microRNAs. MicroRNA array further revealed 140 aberrantly expressed miRNAs out of the 718 miRNAs. The increased expression of miR-205, miR-203, miR-215, miR-34a, and decreased expression of miR-217 were confirmed by qPCR. Comparison of the methylation changes to those of microarray analyses indicates little if any correspondence between gene methylation and gene expression. The increased expression of Xist, Prrc2, Krit1, Nish, and decreased expression of Prss2, Spp1, Col1a2, and Lox were confirmed by qPCR. In summary, in utero arsenic exposure induced global alterations in DNA methylation and aberrant miRNA expression that might contribute to adult adverse outcomes including liver cancer.


Assuntos
5-Metilcitosina/metabolismo , Arsenitos/toxicidade , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Compostos de Sódio/toxicidade , Animais , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Idade Gestacional , Fígado/embriologia , Fígado/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Exposição Materna , Camundongos Endogâmicos C3H , MicroRNAs/genética , Gravidez
8.
Environ Toxicol ; 35(5): 553-560, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31846182

RESUMO

Arsenic (As) can contaminate air, soil, water, and organisms through mobilization of natural mineralogical deposits or anthropogenic actions. Inorganic-As compounds are more toxic and widely available in aquatic environments, including drinking water reservoir catchments. Since little is known about its effects on prepubertal mammals, the present study focused on it. Hence, As was administered through drinking water to male Wistar rats from postnatal day 23 to 53. Negative control group received vehicle only (filtered water); As 1 group received AsNaO2 at 0.01 mg L-1 and As2 group received AsNaO2 at 10 mg L-1 . It was investigated hepatic and renal toxicity of AsNaO2 (ie, histopathology and apoptosis analysis), as well as its mutagenicity (ie, micronucleus test in liver and bone marrow), cytotoxicity (ie, frequency and type of erythrocytes in blood), and genotoxicity (ie, comet assay in blood). Also, As determination was performed in hepatic and renal tissues. Data obtained revealed that immature organisms present a pattern of arsenic accumulation similar to that observed in adults, suggesting similarity in metabolic processes. In addition, liver showed to be an important target tissue for As toxicity in these experimental conditions, exhibiting infiltrate of defense cells, DNA damages, and increased apoptosis rates.


Assuntos
Envelhecimento/efeitos dos fármacos , Arsenitos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dano ao DNA , Poluentes Ambientais/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Compostos de Sódio/toxicidade , Envelhecimento/genética , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Ensaio Cometa , Relação Dose-Resposta a Droga , Masculino , Testes para Micronúcleos , Ratos , Ratos Wistar
9.
Med Sci Monit ; 25: 9923-9932, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874112

RESUMO

BACKGROUND Arsenic (As) is an environmental contaminant, and As pollution in water and soil is a public health issue worldwide. As exposure is associated with the incidence of many disorders, such as arteriosclerosis, diabetes, neurodegenerative diseases, and renal dysfunction. However, the mechanism of As toxicity remains unclear. MATERIAL AND METHODS We investigated the changes in serum protein profiles of rats chronically exposed to As. Twenty healthy rats were randomly divided into 4 groups, and sodium arsenite of varying final concentrations (0, 2, 10, and 50 mg/L, respectively) was add into the drinking water for each group. The administration lasted for 3 months. Two proteomic strategies, isobaric tags for relative and absolute quantitation (iTRAQ), and 2-dimensional gel electrophoresis (2-DE), were employed to screen the differential serum proteins between control and arsenite exposure groups. RESULTS We identified a total of 27 differentially-expressed proteins, among which 9 proteins were significantly upregulated and 18 were downregulated by As exposure. Many of the differentially-expressed proteins were related to fat digestion and absorption, including 5 apolipoproteins, which indicated lipid metabolism may be the most affected by As exposure. CONCLUSIONS This study revealed the influence of As on lipid metabolism, suggesting an increased potential risk of relevant diseases in subjects chronically exposed to As.


Assuntos
Intoxicação por Arsênico/metabolismo , Arsênico/toxicidade , Animais , Arsênico/sangue , Arsênico/metabolismo , Intoxicação por Arsênico/sangue , Arsenitos/farmacologia , Arsenitos/toxicidade , Feminino , Perfilação da Expressão Gênica , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Proteínas , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Compostos de Sódio/farmacologia , Compostos de Sódio/toxicidade
10.
Environ Sci Pollut Res Int ; 26(28): 29257-29266, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396869

RESUMO

An unsafe level of manganese (Mn) was detected in the drinking water in some arsenic (As)-contaminated areas in Bangladesh. Mn is an essential trace element; however, the intake of a higher level of Mn through the drinking water is associated with the development of toxicity in humans. This study was designed to evaluate the effects of As and Mn co-exposure on neurobehavioral and biochemical alterations in a mouse model. Sodium arsenite (10 mg/kg body weight) and manganese chloride tetrahydrate (10 mg/kg body weight) were given to mice individually and in combination with drinking water for 90 days. Results showed that individual As and Mn exposure as well as co-exposure of As and Mn significantly (p < 0.05) reduced the percent of time spent in the open arms when compared with that of control mice. In addition, percent of time spent in open arms significantly (p < 0.05) increased in co-exposed mice compared with As exposure in elevated plus maze (42.05 ± 1.10 versus 38.94 ± 0.66). In the Morris water maze test, the mean time latency to find the platform was longer in metal-treated mice in comparison to that of control mice (p < 0.05). Importantly, the co-exposed group had shorter time when compared with the As-exposed group during the training periods (p < 0.05). Moreover, co-exposed mice stayed significantly (p < 0.05) more time in the target quadrant in the probe trial in comparison with that of As-exposed mice (27.25 ± 1.21 versus 23.83 ± 0.87 s) but less time than control mice (27.25 ± 1.21 versus 43.17 ± 1.49 s). In addition, a significant (p < 0.05) alteration of biochemical parameters such as ALT, AST, ALP, BChE, and SOD as well as urea and creatinine levels were noted in the As-exposed group compared with the control group and Mn significantly (p < 0.05) attenuated the effects of As in co-exposed mice. Therefore, the results of this study suggest that As and Mn may have some antagonistic effect and Mn could attenuate the As-induced neurobehavioral and biochemical alterations in co-exposed mice.


Assuntos
Arsênico/toxicidade , Comportamento Animal/efeitos dos fármacos , Manganês/toxicidade , Animais , Arsenitos/toxicidade , Cloretos/toxicidade , Enzimas/sangue , Aprendizagem/efeitos dos fármacos , Masculino , Compostos de Manganês , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Compostos de Sódio/toxicidade , Memória Espacial/efeitos dos fármacos , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade
11.
Reprod Toxicol ; 89: 136-144, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31310804

RESUMO

Arsenic is a widely dispersed chemical compound in the environment and has been associated with the development of some diseases and different types of cancer. Little is known about the action of arsenic compounds on prostate development during prepuberty and puberty. This study evaluated prostate morphophysiology after sodium arsenite exposure during prepubertal period in rats. Male Wistar rats at PND23 were randomly distributed into three experimental groups (n = 10/group). The Ctrl group (filtered drinking water); As1 group (0.01 mg/L of NaAsO2); As2 group (10.0 mg/L of NaAsO2) that received the diluted solution in drinking water from PND23 to PND53. Histological and molecular analyzes showed developmental delay in the As1 group and important morphophysiological alterations in As2 group. The results showed that exposure to NaAsO2 during prepuberty compromised structural and functional maturation of the prostate in pubertal rats at both doses evaluated in this study.


Assuntos
Envelhecimento/efeitos dos fármacos , Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Próstata/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Compostos de Sódio/toxicidade , Animais , Antioxidantes/metabolismo , Colágeno/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Próstata/patologia , Ratos , Ratos Wistar , Testosterona/sangue
12.
Ecotoxicology ; 28(6): 669-679, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256308

RESUMO

The high level exposure to arsenic induces marked oxidative and genotoxic stress. However, information on the potential of low level arsenic exposure in this context is still scanty. In the present study, the extent of oxidative stress and genetic toxicity induced by low arsenic exposure was explored in freshwater fish Channa punctatus. Fish were exposed to low levels of arsenic (10 and 50 µg L-1) as well as to its high level (500 µg L-1) using sodium arsenite in aquaria water for 14 consecutive days. The TBARS assay for lipid peroxidation exhibited the increased occurrence of oxidative damage in the erythrocytes of fish at both the lower and higher levels of arsenic exposure. The level of reduced glutathione was also elevated in all the three arsenic exposed groups of fish compared to control. In contrast, significant decline was observed in the levels of three major antioxidant enzymes namely, superoxide dismutase, catalase and glutathione peroxidase, upon exposure to higher as well as lower levels of arsenic. Significant increases in micronucleus induction were found in the erythrocytes of fish even at the low levels of arsenic exposure. The study further revealed the occurrence of DNA fragmentation in the erythrocytes of fish at low arsenic exposures as well. The low level exposure to arsenic (using sodium arsenite), therefore, appeared to be capable of inducing noticeable oxidative stress as well as potential genotoxic effect in Channa punctatus. Moreover, the ability of arsenic to induce oxidative stress invariably appeared correlated with its genotoxic potential.


Assuntos
Arsenitos/toxicidade , Dano ao DNA , Peixes/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Arsênico/toxicidade , Biomarcadores/metabolismo , Medição de Risco
14.
Environ Pollut ; 251: 390-399, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100570

RESUMO

Perchlorate is a pervasive, water-soluble contaminant that competitively inhibits the sodium/iodide symporter, reducing the available iodide for thyroid hormone synthesis. Insufficient iodide uptake can lead to hypothyroidism and metabolic syndromes. Because metabolism, obesity and non-alcoholic fatty liver disease (NAFLD) are tightly linked, we hypothesized that perchlorate would act as an obesogen and cause NAFLD via accumulation of lipids in liver of developing threespine stickleback (Gasterosteus aculeatus). We performed an upshift/downshift exposure regime (clean water to perchlorate treated water or perchlorate treated water to clean water) on stickleback embryos at two concentrations (30 mg/L and 100 mg/L) plus the control (0 mg/L) over the course of 305 days. Adult stickleback were euthanized, H&E stained and analyzed for liver morphology. Specifically, we counted the number of lipid droplets, and measured the area of each droplet and the total lipid area of a representative section of liver. We found that perchlorate treated fish had more and larger lipid droplets, and a larger percentage of lipid in their liver than control fish. These data indicate that perchlorate causes NAFLD and hepatic steatosis in stickleback at concentrations commonly found at contaminated sites. These data also indicate the potential of perchlorate to act as an obesogen. Future studies should investigate the obesogenic capacity of perchlorate by examining organ specific lipid accumulation and whether perchlorate induces these effects at concentrations commonly found in drinking water. Work is also needed to determine the mechanisms by which perchlorate induces lipid accumulation.


Assuntos
Exposição Ambiental/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Percloratos/toxicidade , Smegmamorpha/metabolismo , Compostos de Sódio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Smegmamorpha/crescimento & desenvolvimento
15.
J Biochem Mol Toxicol ; 33(7): e22320, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30934151

RESUMO

The present study was aimed at determining the oxidative damage caused by sodium arsenite in 3T3 fibroblast cells and the possible protective role of curcumin (Cur) against sodium arsenite toxicity. Embryonic fibroblast cells were exposed to sodium arsenite (0.01, 0.1, 1, and 10 µM) in the presence and absence of Cur (2.5 µM) for 24 hours. Cell viability, cytotoxicity, lipid peroxidation, hydroxyl radical, hydrogen peroxide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) and expression levels of antioxidant genes (superoxide dismutase, catalase, and glutathione peroxidase) were measured in embryonic fibroblast cells. Results demonstrated that sodium arsenite directly affects antioxidant enzymes and genes in 3T3 embryonic fibroblast cells and induces oxidative damage by increasing the amount of hydrogen peroxide, hydroxyl radical, and lipid peroxidation in the cell. Furthermore, the study indicated that Cur might be a potential ameliorative antioxidant to protect the fibroblast cell toxicity induced by sodium arsenite.


Assuntos
Antioxidantes/farmacologia , Arsenitos/toxicidade , Curcumina/farmacologia , Fibroblastos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/toxicidade , Animais , Células 3T3 BALB , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos
16.
Toxicology ; 420: 73-84, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30978373

RESUMO

Arsenic is a contaminant of food and drinking water. Epidemiological studies have reported correlations between arsenic exposure and neurodevelopmental abnormalities, such as reduced sensory functioning, while in vitro studies have shown that arsenic reduces neurogenesis and alters stem cell differentiation. The goal of this study was assess whether arsenic exposure during embryogenesis reduced olfactory stem cell function and/or numbers, and if so, whether those changes persist into adulthood. Killifish (Fundulus heteroclitus) embryos were exposed to 0, 10, 50 or 200 ppb arsenite (AsIII) until hatching, and juvenile fish were raised in clean water. At 0, 2, 4, 8, 16, 28 and 40 weeks of age, odorant response tests were performed to assess specific olfactory sensory neuron (OSN) function. Olfactory epithelia were then collected for immunohistochemical analysis of stem cell (Sox2) and proliferating cell numbers (PCNA), as well as the number and expression of ciliated (calretinin) and microvillus OSNs (Gαi3) at 0, 4, 16 and 28 weeks. Odorant tests indicated that arsenic exposure during embryogenesis increased the start time of killifish responding to pheromones, and this altered start time persisted to 40 weeks post-exposure. Response to the odorant taurocholic acid (TCA) was also reduced through week 28, while responses to amino acids were not consistently altered. Immunohistochemistry was used to determine whether changes in odorant responses were correlated to altered cell numbers in the olfactory epithelium, using markers of proliferating cells, progenitor cells, and specific OSNs. Comparisons between response to pheromones and PCNA + cells indicated that, at week 0, both parameters in exposed fish were significantly reduced from the control group. At week 28, all exposure are still significantly different than control fish, but now with higher PCNA expression coupled with reduced pheromone responses. A similar trend was seen in the comparisons between Sox2-expressing progenitor cells and response to pheromones, although Sox2 expression in the 28 week-old fish only recovers back to the level of control fish rather than being significantly higher. Comparisons between calretinin expression (ciliated OSNs) and response to TCA demonstrated that both parameters were reduced in the 200 ppb arsenic-exposed fish in at weeks 4, 16, and 28. Correlations between TCA response and the number of PCNA + cells revealed that, at 28 weeks of age, all arsenic exposure groups had reductions in response to TCA, but higher PCNA expression, similar to that seen with the pheromones. Few changes in Gαi3 (microvillus OSNs) were seen. Thus, it appears that embryonic-only exposure to arsenic has long-term reductions in proliferation and differentiation of olfactory sensory neurons, leading to persistent effects in their function.


Assuntos
Arsenitos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fundulidae/embriologia , Neurogênese/efeitos dos fármacos , Neurônios Receptores Olfatórios/efeitos dos fármacos , Olfato/efeitos dos fármacos , Compostos de Sódio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Calbindina 2/metabolismo , Embrião não Mamífero/metabolismo , Feminino , Proteínas de Peixes/metabolismo , Fundulidae/metabolismo , Masculino , Odorantes , Neurônios Receptores Olfatórios/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Fatores de Transcrição SOXB1/metabolismo
17.
Am J Physiol Heart Circ Physiol ; 316(5): H1053-H1064, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30822117

RESUMO

Arsenic is a common contaminant in drinking water throughout the world, and recent studies support a link between inorganic arsenic (iAS) exposure and ischemic heart disease in men and women. Female hearts exhibit an estrogen-dependent reduction in susceptibility to myocardial ischemic injury compared with males, and as such, female hearts may be more susceptible to the endocrine-disrupting effects of iAS exposure. However, iAS exposure and susceptibility to ischemic heart injury have not been examined in mechanistic studies. Male and female mice (8 wk) were exposed to environmentally relevant concentrations of sodium arsenite (0, 10, 100, and 1,000 parts/billion) via drinking water for 4 wk. Pre- and postexposure echocardiography was performed, and postexposure plasma was collected for 17ß-estradiol measurement. Hearts were excised and subjected to ischemia-reperfusion (I/R) injury via Langendorff perfusion. Exposure to 1,000 parts/billion iAS led to sex-disparate effects, such that I/R injury was exacerbated in female hearts but unexpectedly attenuated in males. Assessment of echocardiographic parameters revealed statistically significant structural remodeling in iAS-treated female hearts with no change in function; males showed no change. Plasma 17ß-estradiol levels were not significantly altered by iAS in male or female mice versus nontreated controls. Although total eNOS protein levels did not change in whole heart homogenates from iAS-treated male or female mice, eNOS phosphorylation (Ser1177) was significantly elevated in iAS-treated male hearts. These results suggest that iAS exposure can induce sex-disparate effects and modulate susceptibility to ischemic heart injury by targeting distinct sex-dependent pathways. NEW & NOTEWORTHY This is the first mechanistic study examining iAS exposure on myocardial ischemia-reperfusion injury in male and female mice. Following iAS exposure, ischemia-reperfusion injury was exacerbated in female hearts but attenuated in males. iAS treatment induced statistically significant cardiac remodeling in females, with no change in males. iAS treatment also enhanced phosphorylated eNOS levels at Ser1177, but only in male hearts. These results suggest that iAS alters susceptibility to myocardial I/R injury through distinct sex-dependent pathways.


Assuntos
Arsenitos/toxicidade , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Compostos de Sódio/toxicidade , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiotoxicidade , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Preparação de Coração Isolado , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Fatores Sexuais
18.
Chemosphere ; 224: 280-288, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30825854

RESUMO

Although emerging evidence suggests positive association of arsenic (As) or sulfur dioxide (SO2) exposure with human diseases, reports concerning the effects of co-exposure of As and SO2 are lacking. Moreover, there is insufficient information in the literature about As and SO2 co-exposure to renal injury. In this study, we focus on the environmental problems of excessive As and SO2 that co-exist in many coal consumption areas. We used both C57BL/6 mice and 293T cells to detect toxicities of As and SO2 exposure alone or in combination. Our results showed that co-exposure significantly increased the hazard compared with exposure to As or SO2 alone. Mouse kidney tissue slices showed that co-exposure caused more severe diffuse sclerosing glomerulonephritis than As and SO2 exposure alone. Meanwhile experiments showed that apoptosis was aggravated by co-exposure of As and SO2 in 293T cells. Because As and SO2 cause cell toxicity through increasing oxidative stress, next we detected ROS and other oxidative stress parameters, and the results showed oxidative stress was increased by co-exposure compared with the other three groups. The expression levels of downstream genes in the NF-κB and caspase pathways were higher in the co-exposure group than in the groups of As or SO2 exposure alone in mice and 293T cells. Based on the above results, co-exposure could induce higher toxicity in vitro and in vivo compared with single exposure to As or SO2, indicating that people living in places that contaminated by As and SO2 may have higher chance to get renal injury.


Assuntos
Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , NF-kappa B/metabolismo , Compostos de Sódio/toxicidade , Dióxido de Enxofre/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Células HEK293 , Humanos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
19.
Environ Int ; 126: 454-467, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844581

RESUMO

BACKGROUND: Exposure to arsenic and cadmium is common. Epidemiological and animal studies have suggested that exposure to these two heavy metals can cause metabolic health problems, including type 2 diabetes (T2DM). It has been hypothesized that T2DM could be mediated through the gut microbiome and the metabolites it produces. Although many studies have investigated the association between the gut microbiome and T2DM, few have focused on the connection to arsenic and cadmium. RESULTS: We applied 16S rRNA gene amplicon sequencing and untargeted LC-MS/MS metabolomics to examine the changes in the gut microbiome and metabolite profiles of exposed mice to relevant levels of cadmium and arsenic in the drinking water over two weeks. Cadmium chloride (Cd) exposure significantly changed the mice gut microbiome and resulted in a significantly lower microbial diversity whereas sodium arsenite (As) caused a non-significant decrease in microbial diversity. For Cd and As treatment respectively, we identified 5 and 2 phyla with significant changes and 42 and 24 genera. Bacterial genera that were observed to decline upon both treatments, included several butyrate-producers. Both As and Cd treatment perturbed the metabolome significantly, with 50 ppm Cd compound exposure having the greatest effect when compared to 50 ppm As compound exposure. Two unidentified features were differentially abundant in the As group, while 33 features changed in the Cd group. Differential abundance analysis of all bile acid associated molecular components showed differences under both treatments. Finally, integrative network analysis via bipartite correlation networks suggested that several genera, including the metabolically important Blautia, Eisenbergiella, Clostridium_XlVa, etc. declined in numbers of metabolite interactions. CONCLUSIONS: These results demonstrated that As and Cd exposure caused significant changes to the gut microbiome and metabolome by affecting bile acids, amino acids and taxa associated with metabolic health.


Assuntos
Arsenitos/toxicidade , Cloreto de Cádmio/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Compostos de Sódio/toxicidade , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética
20.
Food Chem Toxicol ; 126: 41-55, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30769048

RESUMO

Arsenic contaminated drinking water consumption is a serious health issue around the world. Chronic inorganic arsenic exposure has been associated with respiratory dysfunctions. It exerts various detrimental effects, disrupting normal cellular homeostasis and turning on severe pulmonary complications. This study elucidated the role of mangiferin, a natural xanthone, against arsenic induced lung toxicity. Chronic exposure of sodium arsenite (NaAsO2) at 10 mg/kg bw for 3 months abruptly increased the LDH release in broncho-alveolar lavage fluid, generated reactive oxygen species (ROS), impaired the antioxidant defense and distorted the alveoli architecture. It caused significant inflammatory outburst and promoted the apoptotic mode of cell death via upregulating the expressions of various proapoptotic molecules related to mitochondrial, extra-mitochondrial and ER stress mediated apoptotic pathway. Activation of inflammatory cascade led to disruption of alveolar capillary barrier and impaired Na+/K+-ATPase function that led to detaining of alveolar fluid clearance activity. Mangiferin due to its anti-inflammatory activity suppressed this inflammation and reduced inflammatory cell infiltration in lung tissue. It significantly restored the antioxidant balance and inhibited apoptosis in lung via upregulating Nrf2-HO1 axis.


Assuntos
Antioxidantes/administração & dosagem , Arsênico/toxicidade , Heme Oxigenase-1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Xantonas/administração & dosagem , Animais , Apoptose , Arsenitos/toxicidade , Heme Oxigenase-1/genética , Humanos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sódio/toxicidade
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