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1.
J Environ Pathol Toxicol Oncol ; 39(2): 149-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749124

RESUMO

Heavy-metal toxicity imposes a potential worldwide threat to the environment and humans. Cadmium, mercury, lead, and arsenic are nonessential toxic heavy metals that are most frequently involved in environmental and health hazards. Conventional chelating agents are unsuitable for subchronic and chronic heavy-metal toxicities. Scientific literature reveals that Spirulina (Arthrospira), a photosynthetic filamentous cyanobacterium that is generally known as blue-green algae, alleviates experimentally induced heavy-metal toxicity. The present review attempts to summarize such studies regarding cadmium, mercury, lead, and arsenic toxicity. A total of 58 preclinical studies demonstrate the alleviative effect of Spirulina against experimental arsenic, cadmium, lead, and mercury toxicities. Five clinical studies reported protective effects of Spirulina against arsenic toxicity in humans. Clinical studies against three heavy metals were not found in the literature. The present literature study appears to show that Spirulina possesses promising heavy-metal toxicity-ameliorative effects that are mainly attributed to its intrinsic antioxidant activity.


Assuntos
Intoxicação por Metais Pesados/prevenção & controle , Metais Pesados/toxicidade , Substâncias Protetoras/farmacologia , Spirulina , Animais , Arsênico/toxicidade , Suplementos Nutricionais , Intoxicação por Metais Pesados/tratamento farmacológico , Humanos
2.
Ecotoxicol Environ Saf ; 204: 110948, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739672

RESUMO

Exposure to arsenic is epidemiologically associated with increased lung disease. In detailing the mechanism by which arsenic exposure leads to disease, studies have emphasized that metabolic reprogramming and immune dysfunction are related to arsenic-induced lung injury. However, the association between the mechanisms listed above is not well understood. Thus, the current study aimed to investigate the interaction of energy metabolism and macrophage polarization, by which arsenic exposure adversely induced lung injury in both in vitro and human studies. First, we confirmed a shift to glycolytic metabolism resulting from mitochondrial dysfunction. This shift was accompanied by an increase in the levels of phosphorylated PDHE1α (S293) and PDK1 and a concomitant marked increase in several key markers of the HIF-1α signaling pathway (HIF-1α, p-PKM2, GLUT1 and HK-2). In addition, utilizing an in vitro model in which lung epithelial cells are cultured with macrophages, we determined that arsenic treatment polarizes macrophages towards the M2 phenotype through lactate. In the human study, the serum lactate and TGF-ß levels were higher in arsenic-exposed subjects than that in reference subjects (t= 4.50, 6.24, both p < 0.05), while FVC and FEV1 were both lower (t= 5.47, 7.59, both p < 0.05). Pearson correlation analyses showed a significant negative correlation between the serum TGF-ß and lactate levels and the lung function parameters (pcorrelation<0.05). In mediation analyses, lactate and TGF-ß significantly mediated 24.3% and 9.0%, respectively, of the association between arsenic and FVC (pmediation<0.05), while lactate and TGF-ß significantly mediated 22.2% and 12.5%, respectively, of the association between arsenic and FEV1 (pmediation<0.05). Together, the results of the in vitro and human studies indicated that there is complex communication between metabolic reprogramming and immune dysfunction, resulting in exacerbated effects in a feedback loop with increased arsenic-induced lung damage.


Assuntos
Arsênico/toxicidade , Metabolismo Energético/efeitos dos fármacos , Lesão Pulmonar/metabolismo , Macrófagos/efeitos dos fármacos , Adulto , Células Epiteliais , Feminino , Humanos , Lesão Pulmonar/etiologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Células THP-1
3.
Ecotoxicol Environ Saf ; 204: 110973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781346

RESUMO

Arsenic (As) exerts a wide range of adverse effects on biological systems, including the reproductive organs in males and females. However, the mechanisms of As-induced reproductive toxicity are mostly obscure. Recently, we showed that autophagy is an essential route for As2O3-induced reprotoxicity through the hypothalamic-pituitary-gonadal-sperm (HPG-S) axis in pubertal and matured F1-male mice. However, the role of autophagy in As2O3- induced ovarian toxicity is mostly unknown. Hence, this study aimed to elucidate the role of oxidative stress, mitochondrial impairment, and autophagic processes in the ovary of As-exposed female mice. For this purpose, mature female mice were challenged with 0, low (0.2), medium (2), and high (20 ppm) As2O3 from 35-days before mating till weaning their pups, and the F1- females from weaning until maturity. Then, all the mice were sacrificed, and oxidative stress parameters, mitochondrial indices, electron microscopic evaluation of the ovaries, expression of autophagic-related genes and proteins, and autophagosome formation were assessed. It was shown that medium and high As2O3 doses were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in the ovary of F1-generation. A dose-dependent increment in the gene expression of PDK1, PI3K, TSC2, AMPK, ULK1, ATG13, Beclin1, ATG12, ATG5, LC3, P62, ATG3, ATG7, and p62, as well as protein expression of Beclin1, and LC3- I, II, was evident in the ovaries of the As-treated animals. Moreover, a dose-dependent decrease in the expression of mTOR and Bcl-2 genes, and mTOR protein was detected with increasing doses of As, suggesting that As treatment-induced autophagy. Along with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles, transmission electron microscopy also confirmed more autophagosomes and injured mitochondria in medium and high As2O3 doses groups. As2O3 also negatively affected the mean body weight, litter size, organ coefficient, and stereological indices in female mice. Finally, in physiological conditions, arsenic trioxide (As2O3) leads to an increased level of autophagy in the oocyte when many oocytes were being lost. These findings indicated that an imbalance in the oxidant-antioxidant system, mitochondrial impairment, and the autophagic process, through inhibition of mTOR, dependent and independent pathways, and Bcl-2, as well as activation of AMPK/PI3K/Beclin1/LC3 routes, could play a pivotal role in As-induced reproductive toxicity through ovarian dysfunction in females.


Assuntos
Arsênico/toxicidade , Autofagia/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Folículo Ovariano/crescimento & desenvolvimento , Ovário/ultraestrutura , Distribuição Aleatória
4.
Toxicol Lett ; 332: 155-163, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32645460

RESUMO

Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects might result in accumulation of dysfunctional organelles and damaged proteins thus promoting tumorigenesis. In the present study, we found that chronic exposure of human bronchial epithelial BEAS-2B cells to sub-lethal dose of sodium arsenite led to autophagy activation and induced an epithelial-to-mesenchymal transition (EMT) to enhance cell migratory and invasive capability. The malignant transformation was mediated via activation of MEK/ERK1/2 signaling. Importantly, inhibition of autophagy in these arsenic-exposed cells by pharmacological intervention or genetic deletion further promoted the EMT and increased the generation of inflammasomes. Both autophagy inhibitor and genetic deletion of autophagy core gene Beclin-1 produced similar effects. These results may suggest the important role of autophagy in sodium arsenite-induced lung tumorigenesis which may serve as a potential target in prevention and treatment of arsenic-imposed lung cancer.


Assuntos
Arsênico/toxicidade , Autofagia/fisiologia , Brônquios/patologia , Neoplasias Brônquicas/induzido quimicamente , Neoplasias Brônquicas/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
5.
Ecotoxicol Environ Saf ; 202: 110851, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32673966

RESUMO

Arsenic is a harmful and toxic substance to the growth and development of plants. Salicylic acid (SA) acts as a signaling molecule, plays pivotal roles in the overall growth and development of plants under various environmental stresses. Artemisinin extracted from the leaves of A. annua helps in malarial treatment. The present investigation is aimed to find out the possible ameliorative role of exogenously-applied salicylic acid (SA) on two varieties of Artemisia annua L., namely 'CIM-Arogya' and 'Jeevan Raksha' under arsenic (As) stress conditions. For this, growth, physiological and biochemical characterization, and artemisinin production was assessed. The various treatments applied on the plants were Control, 10-6 M SA, 10-5 M SA, 45 mg kg-1As, 45 mg kg-1 As + 10-6 M SA, and 45 mg kg-1 As + 10-5 M SA. Arsenic at 45 mg kg-1 of soil, reducing the overall performance of both varieties at 90 and 120 DAP. However, the levels of antioxidants were enhanced in As-stressed plants, and the supplementation of SA further increased these antioxidants in SA-treated plants. It has been observed that minimum reduction in growth and yield occurs with enhanced production of artemisinin in the case of 'CIM-Arogya' compared to 'Jeevan Raksha' under As stress (45 mg kg-1 of soil). Leaf-applied SA significantly increased the content (49.0% & 43.4%) and yield (53.3% & 46.3%) of artemisinin in both tolerant and sensitive varieties as compared to their respective controls. Thus, the variety 'CIM-Arogya' showed tolerant behavior over 'Jeevan Raksha' and is much adapted to higher As stress.


Assuntos
Arsênico/toxicidade , Artemisia annua/fisiologia , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Artemisia annua/crescimento & desenvolvimento , Artemisia annua/metabolismo , Artemisininas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Oxidativo , Folhas de Planta/metabolismo , Ácido Salicílico/farmacologia , Solo , Estresse Fisiológico/efeitos dos fármacos
6.
Life Sci ; 257: 118132, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710949

RESUMO

AIM: Arsenic, an environmental contaminant, represents a public health problem worldwide. Studies have shown its association with molecular mechanisms related to cardiomyocytes redox balance. However, the microstructure and ultrastructure of cardiac tissue, as well as the activity of its antioxidant defenses front of disturbances in the mineral bioavailability induced by arsenic are still scarce. Thus, the aim of this study was to evaluate if arsenic exposure might induce structural and ultrastructural damages in cardiac tissue, including pathological remodeling of the parenchyma and stroma. Moreover, its impact on micromineral distribution and antioxidant enzymes activity in heart tissue was also evaluated. MAIN METHODS: Adult male Wistar rats were divided into three groups that received 0, 1 and 10 mg/L sodium arsenite in drinking water for eight weeks. The hearts were collected and subjected to structural and ultrastructural analysis, mineral microanalysis and antioxidant enzymes quantification. Functional markers of cardiac damages were evaluated using serum samples. KEY FINDINGS: Arsenic exposure induced dose-dependent structural and ultrastructural remodeling of cardiac tissue, with parenchyma loss, increase of stroma components, collagen deposition, and pathological damages such as inflammation, sarcomere disorganization, mitochondria degeneration and myofilament dissociation. Moreover, this metalloid was bioaccumulated in the tissue affecting its micromineral content, which resulted in antioxidant imbalance and increased levels of oxidative stress and cardiac markers. SIGNIFICANCE: Taken together, our findings indicate that the heart is a potential target to arsenic toxicity, and long-term exposure to this metalloid must be avoided, once it might induce several cardiac tissue pathologies.


Assuntos
Arsênico/toxicidade , Coração/efeitos dos fármacos , Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Arsênico/administração & dosagem , Arsênico/análise , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa Transferase/metabolismo , Masculino , Miocárdio/química , Miocárdio/ultraestrutura , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
7.
Chemosphere ; 259: 127410, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32615455

RESUMO

Arsenic (As) can be present naturally in groundwater from peanut fields, constituting a serious problem, as roots can accumulate and mobilize the metalloid to their edible parts. Understanding the redox changes in the legume exposed to As may help to detect potential risks to human health and recognize tolerance mechanisms. Thirty-days old peanut plants inoculated with Bradyrhizobium sp. strains (SEMIA6144 or C-145) were exposed to a realistic arsenate concentration, in order to unravel the redox response and characterize the oxidative stress indexes. Thus, root anatomy, reactive oxygen species detection by fluorescence microscopy and, ROS histochemical staining along with the NADPH oxidase activity were analyzed. Besides, photosynthetic pigments and damage to lipids and proteins were determined as oxidative stress indicators. Results showed that at 3 µM AsV, the cross-section areas of peanut roots were augmented; NADPH oxidase activity was significantly increased and O2˙¯and H2O2 accumulated in leaves and roots. Likewise, an increase in the lipid peroxidation and protein carbonyls was also observed throughout the plant regardless the inoculated strain, while chlorophylls and carotenes were increased only in those inoculated with Bradyrhizobium sp. C-145. Interestingly, the oxidative burst, mainly induced by the NADPH oxidase activity, and the consequent oxidative stress was strain-dependent and organ-differential. Additionally, As modifies the root anatomy, acting as a possibly first defense mechanism against the metalloid entry. All these findings allowed us to conclude that the redox response of peanut is conditioned by the rhizobial strain, which contributes to the importance of effectively formulating bioinoculants for this crop.


Assuntos
Arachis/microbiologia , Arsênico/toxicidade , Bradyrhizobium/fisiologia , Estresse Oxidativo/fisiologia , Arachis/efeitos dos fármacos , Arachis/metabolismo , Arachis/fisiologia , Arseniatos , Arsênico/metabolismo , Bradyrhizobium/efeitos dos fármacos , Bradyrhizobium/metabolismo , Clorofila/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos , Oxirredução , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Simbiose/efeitos dos fármacos
8.
Sci Total Environ ; 745: 140926, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32712499

RESUMO

Arsenic, copper, and zinc are common elements found in contaminated soils but little is known about their combined effects on plants when presented simultaneously. Here, we systematically investigated the phytotoxicity and uptake of binary and ternary mixtures of As, Cu, and Zn in a soil-plant system, using wheat (Triticum aestivum) as model species. The reference models of concentration addition (CA) and response addition (RA) coupled with different expressions of exposure (total concentrations in soil ([M]tot, mg/kg), free ion activities in soil solution ({M}, µM), and internal concentrations in plant roots ([M]int, µg/g)), were selected to assess the interaction mechanisms of binary mixtures of AsCu, AsZn, and CuZn. Metal(loid) interactions in soil were estimated in terms of solution-solid partitioning, root uptake, and root elongation effects. The partitioning of one metal(loid) between the soil solution and solid phase was most often inhibited by the presence of the other metal(loid). In terms of uptake, inhibitory effects and no effects were observed in the mixtures of As, Cu, and Zn, depending on the mixture combinations and the dose metrics used. In terms of toxicity, simple (antagonistic or synergistic) and more complex (dose ratio-dependent or dose level-dependent) interaction patterns of binary mixtures occurred, depending on the dose metrics selected and the reference models used. For ternary mixtures (As-Cu-Zn), nearly additive effects were observed irrespective of dose descriptors and reference models. The observed interactions in this study may help to understand and predict the joint toxicity of metal(loid)s mixtures in soil-plant system. Mixture interactions and bioavailability should be incorporated into the regulatory framework for accurate risk assessment of multimetal-contaminated sites.


Assuntos
Arsênico/toxicidade , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Cobre/toxicidade , Solo , Triticum/efeitos dos fármacos , Zinco/análise , Zinco/toxicidade
9.
Proc Natl Acad Sci U S A ; 117(25): 13975-13982, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513708

RESUMO

Arsenic is a toxic pollutant commonly found in the environment. Most of the previous studies on arsenic pollution have primarily focused on arsenic contamination in groundwater. In this study, we examine the impact on human health from atmospheric arsenic on the global scale. We first develop an improved global atmospheric arsenic emission inventory and connect it to a global model (Goddard Earth Observing System [GEOS]-Chem). Model evaluation using observational data from a variety of sources shows the model successfully reproduces the spatial distribution of atmospheric arsenic around the world. We found that for 2005, the highest airborne arsenic concentrations were found over Chile and eastern China, with mean values of 8.34 and 5.63 ng/m3, respectively. By 2015, the average atmospheric arsenic concentration in India (4.57 ng/m3) surpassed that in eastern China (4.38 ng/m3) due to the fast increase in coal burning in India. Our calculation shows that China has the largest population affected by cancer risk due to atmospheric arsenic inhalation in 2005, which is again surpassed by India in 2015. Based on potential exceedance of health-based limits, we find that the combined effect by including both atmospheric and groundwater arsenic may significantly enhance the risks, due to carcinogenic and noncarcinogenic effects. Therefore, this study clearly implies the necessity in accounting for both atmospheric and groundwater arsenic in future management.


Assuntos
Poluentes Atmosféricos/toxicidade , Intoxicação por Arsênico/epidemiologia , Arsênico/toxicidade , Saúde Global/estatística & dados numéricos , Modelos Estatísticos , Neoplasias/epidemiologia , Poluentes Atmosféricos/análise , Arsênico/análise , Atmosfera/química , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental , Água Subterrânea/química , Humanos , Análise Espaço-Temporal
10.
Chemosphere ; 258: 127284, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32563913

RESUMO

The exposition of mate (Ilex Paraguariensis A. St.-Hil.) to As and Cd was investigated in plants derived from young mini-cuttings. Mate plants were cultivated in a closed soilless system, composed of coarse sand as substrate and flood fertirrigation. Plantlets were fertirrigated with nutritive solution and As and Cd solutions were added to the nutritive solution in the final concentration of 8 and 17 mg L-1 (As) and of 17 and 33 mg L-1 (Cd) during 14 days. Results show that stem diameter and Dickson quality index (DQI) variables could not be used as a potential indicator of accumulation of As and Cd. The shoot height, number of leaves and chlorophyll index are variables easy and quick to measure and they can be used as parameters to evaluate the stress caused in mate plants cultivation in a closed soilless system. The highest concentration of As and Cd was in roots of plants. Beyond the roots, As and Cd also can be translocated to the leaves achieving high concentrations. In addition, leaves from the treated mate plants were submitted to a hot infusion extraction in order to simulate the traditional beverage and As and Cd were determined in the infusion. Regarding to the infusion procedure, considerable As and Cd amounts were extracted from the leaves leading to conclude that this way of consumption can be an important source of toxic elements for the human diet.


Assuntos
Arsênico/toxicidade , Cádmio/farmacocinética , Contaminação de Alimentos/análise , Ilex paraguariensis/efeitos dos fármacos , Folhas de Planta/química , Cádmio/toxicidade , Exposição Dietética , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/toxicidade , Humanos , Extratos Vegetais/análise , Extratos Vegetais/química , Raízes de Plantas/química , Chás de Ervas , Distribuição Tecidual
11.
Ecotoxicol Environ Saf ; 201: 110735, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32480163

RESUMO

Methyl jasmonate (Me-JA) is a plant growth regulator known for modulating plant responses to various abiotic and biotic stresses. The unavoidable arsenic (As) contamination in rice (Oryza sativa) results in reduced crop yield and greater carcinogenic risk to humans. The present work examines the significance of Me-JA induced molecular signaling and tolerance towards arsenic toxicity in rice. The arsenite (AsIII; 25 µM) stress hampered the overall growth and development of the rice seedling. However, the co-application (25 µM AsIII+0.25 µM Me-JA) resulted in increased biomass, chlorophyll content, enhanced antioxidant enzyme activities as compared to AsIII treated plants. The co-application also demonstrated a marked decrease in malondialdehyde content, electrolyte leakage and accumulation of total AsIII content (root + shoot) as compared to AsIII treated plants. The co-application also modulated the expression of genes involved in downstream JA signaling pathway (OsCOI, OsJAZ3, OsMYC2), AsIII uptake (OsLsi1, OsLsi2, OsNIP1;1, OsNIP3;1), translocation (OsLsi6, and OsINT5) and detoxification (OsNRAMP1, OsPCS2, and OsABCC2) which revealed the probable adaptive response of the rice plant to cope up arsenic stress. Our findings reveal that Me-JA alleviates AsIII toxicity by modulating signaling components involved in As uptake, translocation, and detoxification and JA signaling in rice. This study augments our knowledge for the future use of Me-JA in improving tolerance against AsIII stress.


Assuntos
Acetatos/farmacologia , Arsênico/toxicidade , Ciclopentanos/farmacologia , Oryza/efeitos dos fármacos , Oxilipinas/farmacologia , Reguladores de Crescimento de Planta/farmacologia , Acetatos/metabolismo , Arsênico/metabolismo , Arsenitos/metabolismo , Arsenitos/toxicidade , Transporte Biológico , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Humanos , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos
12.
PLoS One ; 15(6): e0234965, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574193

RESUMO

There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (⊔20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.


Assuntos
Arsênico/toxicidade , Exposição Ambiental/efeitos adversos , Fumar/imunologia , Linfócitos T/efeitos dos fármacos , Vitamina D/sangue , Adulto , Idoso , Arsênico/urina , Bangladesh/epidemiologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/epidemiologia , Linfócitos T/imunologia , Vitamina D/imunologia
13.
Chemosphere ; 258: 127305, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32563914

RESUMO

Chronic arsenic toxicity has become a global concern due to its adverse pathophysiological outcome and carcinogenic potential. It is already established that arsenic induced reactive oxygen species alters mitochondrial functionality. Major regulatory genes for mitochondrial biogenesis, i.e., PGC1α, Tfam, NRF1and NRF2 are located in the nucleus. As a result, mitochondria-nucleus crosstalk is crucial for proper mitochondrial function. This previous hypothesis led us to investigateinvolvement of epigenetic alteration behindenhanced mitochondrial biogenesis in chronic arsenic exposure. An extensive case-control study was conducted with 390 study participants (unexposed, exposed without skin lesion, exposed with skin lesion and exposed skin tumour) from highly arsenic exposed areas ofWest Bengal, India. Methylation specific PCRrevealed significant promoter hypomethylation oftwo key biogenesis regulatory genes, PGC1αandTfam in arsenic exposed individuals and also in skin tumour tissues. Linear regression analysis indicated significant negative correlation between urinary arsenic concentration and promoter methylation status. Increased expression of biogenesis regulatory genes wasobtained by quantitative real-time PCR analysis. Moreover, altered mitochondrial fusion-fission regulatory gene expression was also observed in skin tumour tissues. miR663, having tumour suppressor gene like function was known to be epigenetically regulated through mitochondrial retrograde signal. Promoter hypermethylation with significantly decreased expression of miR663 was found in skin cancer tissues compared to non-cancerous control tissue. In conclusion, results indicated crucial role of epigenetic alteration in arsenic induced mitochondrial biogenesis and arsenical skin carcinogenesis for the first time. However, further mechanistic studies are necessary for detailed understanding of mitochondria-nucleus crosstalk in arsenic perturbation.


Assuntos
Arsênico/toxicidade , Epigênese Genética , Mitocôndrias/fisiologia , Arsênico/metabolismo , Intoxicação por Arsênico , Carcinogênese/induzido quimicamente , Estudos de Casos e Controles , Metilação de DNA , Epigenômica , Feminino , Humanos , Índia , Masculino , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Biogênese de Organelas , Regiões Promotoras Genéticas , Dermatopatias/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente
14.
Artigo em Inglês | MEDLINE | ID: mdl-32588237

RESUMO

Chromated copper arsenate (CCA) mixtures were used in the past for wood preservation, leading to large scale soil contamination. This study aimed at contributing to the risk assessment of CCA-contaminated soils by assessing the toxicity of binary mixtures of copper, chromium and arsenic to the earthworm Eisenia andrei in OECD artificial soil. Mixture effects were related to reference models of Concentration Addition (CA) and Independent Action (IA) using the MIXTOX model, with effects being related to total and available (H2O and 0.01 M CaCl2 extractable) concentrations in the soil. Since only in mixtures with arsenic dose-related mortality occurred (LC50 92.5 mg/kg dry soil), it was not possible to analyze the mixture effects on earthworm survival with the MIXTOX model. EC50s for effects of Cu, Cr and As on earthworm reproduction, based on total soil concentrations, were 154, 449 and 9.1 mg/kg dry soil, respectively. Effects of mixtures were mainly antagonistic when related to the CA model but additive related to the IA model. This was the case when mixture effects were based on total and H2O-extractable concentrations; when based on CaCl2-extractable concentrations effects mainly were additive related to the CA model except for the Cr-As mixture which acted antagonistically. These results suggest that the CCA components do interact leading to a reduced toxicity when present in a mixture.


Assuntos
Arsênico/toxicidade , Cromo/toxicidade , Cobre/toxicidade , Oligoquetos/efeitos dos fármacos , Poluentes do Solo/toxicidade , Animais , Arseniatos/toxicidade , Testes de Toxicidade
15.
Ecotoxicol Environ Saf ; 200: 110756, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464442

RESUMO

Arsenic is a recognized highly toxic contaminant, responsible for numerous human diseases and affecting many millions of people in different parts of the world. Contrarily, curcumin is a natural dietary polyphenolic compound and the main active ingredient in turmeric. Recently it has drawn great attention due to its diverse biological activities, strong antioxidant properties and therapeutic potential against many human ailments. In this study, we aimed to explore the protective effects and the regulatory role of curcumin on arsenic-induced toxicity and gain insights into biomolecular mechanism/s. Arsenic (10 µM) treatment in PC12 cells for 24 h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. In addition, arsenic caused apoptotic cell death in PC12 cells, which were confirmed from flow cytometry results. Moreover, arsenic (10 µM) treatment significantly down-regulated the inhibition factors of autophagy/apoptosis; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap protein expressions, up-regulated the enhanced factors of autophagy/apoptosis; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 proteins and eventually caused autophagic and apoptotic cell death. However, curcumin (2.5 µM) pretreatment with arsenic (10 µM) effectively saves PC12 cells against arsenic-induced cytotoxicity through increasing cell viability, intracellular GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic expressively alleviated arsenic-induced toxicity and cell death by reversing the expressions of proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap, ULK, LC3, p53, Bax, cytochrome c, caspase 9 and cleaved caspase 3. Our findings indicated that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and alleviates arsenic-triggered toxicity in PC12 cells by regulating autophagy/apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Arsênico/toxicidade , Autofagia/efeitos dos fármacos , Curcumina/farmacologia , Poluentes Ambientais/toxicidade , Animais , Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos
16.
Science ; 368(6493): 845-850, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32439786

RESUMO

Naturally occurring arsenic in groundwater affects millions of people worldwide. We created a global prediction map of groundwater arsenic exceeding 10 micrograms per liter using a random forest machine-learning model based on 11 geospatial environmental parameters and more than 50,000 aggregated data points of measured groundwater arsenic concentration. Our global prediction map includes known arsenic-affected areas and previously undocumented areas of concern. By combining the global arsenic prediction model with household groundwater-usage statistics, we estimate that 94 million to 220 million people are potentially exposed to high arsenic concentrations in groundwater, the vast majority (94%) being in Asia. Because groundwater is increasingly used to support growing populations and buffer against water scarcity due to changing climate, this work is important to raise awareness, identify areas for safe wells, and help prioritize testing.


Assuntos
Intoxicação por Arsênico/etiologia , Arsênico/análise , Arsênico/toxicidade , Mudança Climática , Exposição Ambiental , Água Subterrânea/química , Água Potável/análise , Humanos , Aprendizado de Máquina , Modelos Teóricos
17.
PLoS One ; 15(5): e0233055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413087

RESUMO

Given the close relationship between cytokinins (CKs), photosynthesis and nitrogen metabolism, this study assessed the effect of arsenic (As) contamination on these metabolic components in the As-hyperaccumulators Pteris cretica L. var. Albo-lineata (Pc-A) and var. Parkerii (Pc-P) as well as the As-non-hyperaccumulator Pteris straminea Mett. ex Baker (Ps). The ferns were cultivated in a pot experiment for 23 weeks in soil spiked with As at the levels 20 and 100 mg·kg-1. For the purpose of this study, the CKs were placed into five functionally different groups according to their structure and physiological roles: bioactive forms (bCKs; CK free bases); inactive or weakly active forms (dCKs; CK N-glucosides); transport forms (tCKs; CK ribosides); storage forms (sCKs; O-glucosides); and primary products of CK biosynthesis (ppbCKs; CK nucleotides). An important finding was higher CKs total content, accumulation of sCKs and reduction of dCKs in As-hyperaccumulators in contrast to non-hyperaccumulator ferns. A significant depletion of C resources was confirmed in ferns, especially Ps, which was determined by measuring the photosynthetic rate and chlorophyll fluorescence. A fluorescence decrease signified a reduction in the C/N ratio, inducing an increase of bioactive CKs forms in Pc-P and Ps. The impact of As on N utilization was significant in As-hyperaccumulators. The glutamic acid/glutamine ratio, an indicator of primary N assimilation, diminished in all ferns with increased As level in the soil. In conclusion, the results indicate a large phenotypic diversity of Pteris species to As and suggest that the CKs composition and the glutamic acid/glutamine ratio can be used as a tool to diagnose As stress in plants.


Assuntos
Arsênico/toxicidade , Citocininas/metabolismo , Nitrogênio/metabolismo , Pteris/efeitos dos fármacos , Pteris/metabolismo , Aminoácidos/metabolismo , Biomassa , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Pteris/crescimento & desenvolvimento , Poluentes do Solo/toxicidade
18.
Ecotoxicol Environ Saf ; 200: 110768, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460053

RESUMO

Consuming arsenic (As)-contaminated vegetables is the main route of As exposure in humans. The present study focused on the alterations in antioxidant enzymatic activities and As bioaccessibility in As-contaminated radish subjected to Se. Compared to the CK group, the total As content in raw radish was reduced by 27.5 ± 1.3%, and the bioaccessibility of As was reduced by 21.9 ± 2.3% in the 6 mg Se kg-1 treatment group. The total As content in the treatment groups decreased first but then increased with increasing Se application in raw radish, gastric (G) fraction and gastrointestinal (GI) fraction, while the antioxidant activity exhibited the opposite trend. The results revealed that a low amount of Se effectively blocks the accumulation of As in radish, improves the antioxidant activity in radish and reduces the bioaccessibility of As. These findings provide new ideas for effectively alleviating the spread of As to the human body through the food chain.


Assuntos
Antioxidantes/farmacologia , Arsênico/toxicidade , Raphanus/efeitos dos fármacos , Selênio/farmacologia , Poluentes do Solo/toxicidade , Verduras/efeitos dos fármacos , Arsênico/metabolismo , Bioacumulação/efeitos dos fármacos , Disponibilidade Biológica , Digestão , Humanos , Modelos Teóricos , Raphanus/enzimologia , Raphanus/metabolismo , Poluentes do Solo/metabolismo , Verduras/enzimologia , Verduras/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-32353678

RESUMO

Nitric oxide (NO) has signalling roles in plant stress responses. Cadmium (Cd) and arsenic (As) soil pollutants alter plant development, mainly the root-system, by increasing NO-content, triggering reactive oxygen species (ROS), and forming peroxynitrite by NO-reaction with the superoxide anion. Interactions of NO with ROS and peroxynitrite seem important for plant tolerance to heavy metal(oid)s, but the mechanisms underlying this process remain unclear. Our goal was to investigate NO-involvement in rice (Oryza sativa L.) root-system after exposure to Cd or As, to highlight possible differences in NO-behaviour between the two pollutants. To the aim, morpho-histological, chemical and epifluorescence analyses were carried out on roots of different origin in the root-system, under exposure to Cd or As, combined or not with sodium nitroprusside (SNP), a NO-donor compound. Results show that increased intracellular NO levels alleviate the root-system alterations induced by Cd, i.e., inhibition of adventitious root elongation and lateral root formation, increment in lignin deposition in the sclerenchyma/endodermis cell-walls, but, even if reducing As-induced endodermis lignification, do not recover the majority of the As-damages, i.e., enhancement of AR-elongation, reduction of LR-formation, anomalous tissue-proliferation. However, NO decreases both Cd and As uptake, without affecting the pollutants translocation-capability from roots to shoots. Moreover, NO reduces the Cd-induced, but not the As-induced, ROS levels by triggering peroxynitrite production. Altogether, results highlight a different behaviour of NO in modulating rice root-system response to the toxicity of the heavy metal Cd and the metalloid As, which depends by the NO-interaction with the specific pollutant.


Assuntos
Arsênico , Cádmio , Óxido Nítrico , Oryza , Raízes de Plantas , Arsênico/toxicidade , Cádmio/toxicidade , Óxido Nítrico/farmacologia , Oryza/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Poluentes do Solo/toxicidade
20.
Environ Health Prev Med ; 25(1): 16, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460744

RESUMO

Well water could be a stable source of drinking water. Recently, the use of well water as drinking water has been encouraged in developing countries. However, many kinds of disorders caused by toxic elements in well drinking water have been reported. It is our urgent task to resolve the global issue of element-originating diseases. In this review article, our multidisciplinary approaches focusing on oncogenic toxicities and disturbances of sensory organs (skin and ear) induced by arsenic and barium are introduced. First, our environmental monitoring in developing countries in Asia showed elevated concentrations of arsenic and barium in well drinking water. Then our experimental studies in mice and our epidemiological studies in humans showed arsenic-mediated increased risks of hyperpigmented skin and hearing loss with partial elucidation of their mechanisms. Our experimental studies using cultured cells with focus on the expression and activity levels of intracellular signal transduction molecules such as c-SRC, c-RET, and oncogenic RET showed risks for malignant transformation and/or progression arose from arsenic and barium. Finally, our original hydrotalcite-like compound was proposed as a novel remediation system to effectively remove arsenic and barium from well drinking water. Hopefully, comprehensive studies consisting of (1) environmental monitoring, (2) health risk assessments, and (3) remediation will be expanded in the field of environmental health to prevent various disorders caused by environmental factors including toxic elements in drinking water.


Assuntos
Arsênico/toxicidade , Bário/toxicidade , Água Potável/análise , Exposição Ambiental , Poluentes Químicos da Água/toxicidade , Animais , Saúde Ambiental , Monitoramento Ambiental , Humanos , Camundongos , Poços de Água
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