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1.
Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects.
Stýblo, M, Venkatratnam, A, Fry, RC, Thomas, DJ
Archives of toxicology. 2021;(5):1547-1572
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Abstract
The toxic metalloid inorganic arsenic (iAs) is widely distributed in the environment. Chronic exposure to iAs from environmental sources has been linked to a variety of human diseases. Methylation of iAs is the primary pathway for metabolism of iAs. In humans, methylation of iAs is catalyzed by arsenic (+ 3 oxidation state) methyltransferase (AS3MT). Conversion of iAs to mono- and di-methylated species (MAs and DMAs) detoxifies iAs by increasing the rate of whole body clearance of arsenic. Interindividual differences in iAs metabolism play key roles in pathogenesis of and susceptibility to a range of disease outcomes associated with iAs exposure. These adverse health effects are in part associated with the production of methylated trivalent arsenic species, methylarsonous acid (MAsIII) and dimethylarsinous acid (DMAsIII), during AS3MT-catalyzed methylation of iAs. The formation of these metabolites activates iAs to unique forms that cause disease initiation and progression. Taken together, the current evidence suggests that methylation of iAs is a pathway for detoxification and for activation of the metalloid. Beyond this general understanding of the consequences of iAs methylation, many questions remain unanswered. Our knowledge of metabolic targets for MAsIII and DMAsIII in human cells and mechanisms for interactions between these arsenicals and targets is incomplete. Development of novel analytical methods for quantitation of MAsIII and DMAsIII in biological samples promises to address some of these gaps. Here, we summarize current knowledge of the enzymatic basis of MAsIII and DMAsIII formation, the toxic actions of these metabolites, and methods available for their detection and quantification in biomatrices. Major knowledge gaps and future research directions are also discussed.
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Arsenic and selenium measurements in nail and hair show important relationships to Alzheimer's disease in the elderly.
Koseoglu, E, Kutuk, B, Nalbantoglu, OU, Koseoglu, R, Kendirci, M
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2021;:126684
Abstract
BACKGROUND AND RESEARCH QUESTION The relationships of Arsenic (As) and selenium (Se) to Alzheimer's Disease (AD) are not clearly known. This case-control observational study aims to investigate the possible relationship of these elements to the diagnosis and pathophysiology of the disease. METHODS This case-control observational study was performed using 40 AD patients in different clinical stages and 40 healthy control subjects, living in a similar environment with low As exposure. The levels of As and Se in nail and hair were measured with Inductively Coupled Plasma Mass Spectrometry. The results were analysed with regards to clinical condition, age, disease duration, sex, education, living environment, and the relationship of the two elements using Mann Whitney U test and Spearman Rho or Pearson correlation tests as appropriate. RESULTS The levels of As and Se were not related to age, disease duration, sex, education, or living environment in the study groups (p > 0.05). The levels of As and Se in hair and nail samples of all patients and patient subgroups were higher than those in the healthy subjects (p < 0.001). A positive correlation was found between the levels of As and Se in both hair and nail samples only in the patient group (p < 0.01). CONCLUSION According to the results, As and Se levels probably increase due to some metabolic or genetic factors affecting both of them together. There may be an increase in the unregulated pool (selenomethionine) and a decrease in the regulated pool of Se (selenosycteine) in AD. Our findings need verification and the subject seems to deserve more elaborate evaluations including genetic analyses and analysis of different chemical forms of these elements.
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Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes.
Bozack, AK, Boileau, P, Wei, L, Hubbard, AE, Sillé, FCM, Ferreccio, C, Acevedo, J, Hou, L, Ilievski, V, Steinmaus, CM, et al
Environmental health : a global access science source. 2021;(1):79
Abstract
BACKGROUND Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. METHODS DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. RESULTS In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. CONCLUSIONS Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.
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A State-of-the-Science Review of Arsenic's Effects on Glucose Homeostasis in Experimental Models.
Castriota, F, Rieswijk, L, Dahlberg, S, La Merrill, MA, Steinmaus, C, Smith, MT, Wang, JC
Environmental health perspectives. 2020;(1):16001
Abstract
BACKGROUND The prevalence of type 2 diabetes (T2D) has more than doubled since 1980. Poor nutrition, sedentary lifestyle, and obesity are among the primary risk factors. While an estimated 70% of cases are attributed to excess adiposity, there is an increased interest in understanding the contribution of environmental agents to diabetes causation and severity. Arsenic is one of these environmental chemicals, with multiple epidemiology studies supporting its association with T2D. Despite extensive research, the molecular mechanism by which arsenic exerts its diabetogenic effects remains unclear. OBJECTIVES We conducted a literature search focused on arsenite exposure in vivo and in vitro, using relevant end points to elucidate potential mechanisms of oral arsenic exposure and diabetes development. METHODS We explored experimental results for potential mechanisms and elucidated the distinct effects that occur at high vs. low exposure. We also performed network analyses relying on publicly available data, which supported our key findings. RESULTS While several mechanisms may be involved, our findings support that arsenite has effects on whole-body glucose homeostasis, insulin-stimulated glucose uptake, glucose-stimulated insulin secretion, hepatic glucose metabolism, and both adipose and pancreatic β-cell dysfunction. DISCUSSION This review applies state-of-the-science approaches to identify the current knowledge gaps in our understanding of arsenite on diabetes development. https://doi.org/10.1289/EHP4517.
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Microbes involved in arsenic mobilization and respiration: a review on isolation, identification, isolates and implications.
Mazumder, P, Sharma, SK, Taki, K, Kalamdhad, AS, Kumar, M
Environmental geochemistry and health. 2020;(10):3443-3469
Abstract
Microorganisms play an important role in arsenic (As) cycling in the environment. Microbes mobilize As directly or indirectly, and natural/geochemical processes such as sulphate and iron reduction, oxidative sulphide mineral dissolution, arsenite (AsO33-) oxidation and arsenate (AsO43-) respiration further aid in As cycle in the environment. Arsenate serves as an electron donor for the microbes during anaerobic conditions in the sediment. The present work reviews the recent development in As contamination, various As-metabolizing microbes and their phylogenetic diversity, to understand the role of microbial communities in As respiration and mobilization. It also summarizes the contemporary understanding of the intricate biochemistry and molecular biology of natural As metabolisms. Some successful examples of engineered microbes by harnessing these natural mechanisms for effective remediation are also discussed. The study indicates that there is an exigent need to have a clear understanding of environmental aspects of As mobilization and subsequent oxidation-reduction by a suitable microbial consortium.
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Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.
Tam, LM, Price, NE, Wang, Y
Chemical research in toxicology. 2020;(3):709-726
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Abstract
Exposure to arsenic in contaminated drinking water is an emerging public health problem that impacts more than 200 million people worldwide. Accumulating lines of evidence from epidemiological studies revealed that chronic exposure to arsenic can result in various human diseases including cancer, type 2 diabetes, and neurodegenerative disorders. Arsenic is also classified as a Group I human carcinogen. In this review, we survey extensively different modes of action for arsenic-induced carcinogenesis, with focus being placed on arsenic-mediated impairment of DNA repair pathways. Inorganic arsenic can be bioactivated by methylation, and the ensuing products are highly genotoxic. Bioactivation of arsenicals also elicits the production of reactive oxygen and nitrogen species (ROS and RNS), which can directly damage DNA and modify cysteine residues in proteins. Results from recent studies suggest zinc finger proteins as crucial molecular targets for direct binding to As3+ or for modifications by arsenic-induced ROS/RNS, which may constitute a common mechanism underlying arsenic-induced perturbations of DNA repair.
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Scenario, perspectives and mechanism of arsenic and fluoride Co-occurrence in the groundwater: A review.
Kumar, M, Goswami, R, Patel, AK, Srivastava, M, Das, N
Chemosphere. 2020;:126126
Abstract
Arsenic (As) and fluoride (F-) are the two most conspicuous contaminants, in terms of distribution and menace, in aquifers around the world. While the majority of studies focus on the individual accounts of their hydro-geochemistry, the current work is an effort to bring together the past and contemporary works on As and F- co-occurrence. Co-occurrence in the context of As and F- is a broad umbrella term and necessarily does not imply a positive correlation between the two contaminants. In arid oxidized aquifers, healthy relationships between As and F- is reported owing desorption based release from the positively charged (hydr)oxides of metals like iron (Fe) under alkaline pH. In many instances, multiple pathways of release led to little or no correlation between the two, yet there were high concentrations of both at the same time. The key influencer of the strength of the co-occurrence is seasonality, environment, and climatic conditions. Besides, the existing primary ion and dissolved organic matter also affect the release and enrichment of As-F- in the aquifer system. Anthropogenic forcing in the form of mining, irrigation return flow, extraction, recharge, and agrochemicals remains the most significant contributing factor in the co-occurrence. The epidemiological indicate that the interface of these two interacting elements concerning public health is considerably complicated and can be affected by some uncertain factors. The existing explanations of interactions between As-F are indecisive, especially their antagonistic interactions that need further investigation. "Multi-contamination perspectives of groundwater" is an essential consideration for the overarching question of freshwater sustainability.
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Response of cytokinins and nitrogen metabolism in the fronds of Pteris sp. under arsenic stress.
Pavlíková, D, Zemanová, V, Pavlík, M, Dobrev, PI, Hnilička, F, Motyka, V
PloS one. 2020;(5):e0233055
Abstract
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.
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Bioremediation of toxic heavy metals (THMs) contaminated sites: concepts, applications and challenges.
Rahman, Z, Singh, VP
Environmental science and pollution research international. 2020;(22):27563-27581
Abstract
Heavy metal contamination is a global issue, where the prevalent contaminants are arsenic (As), cadmium (Cd), chromium (Cr)(VI), mercury (Hg), and lead (Pb). More often, they are collectively known as "most problematic heavy metals" and "toxic heavy metals" (THMs). Their treatment through a variety of biological processes is one of the prime interests in remediation studies, where heavy metal-microbe interaction approaches receive high interest for their cost effective and ecofriendly solutions. In this review, we provide an up to date information on different microbial processes (bioremediation) for the removal of THMs. For the same, emphasis is put on oxidation-reduction, biomineralization, bioprecipitation, bioleaching, biosurfactant technology, biovolatilization, biosorption, bioaccumulation, and microbe-assisted phytoremediation with their selective advantages and disadvantages. Further, the literature briefly discusses about the various setups of cleaning processes of THMs in environment under ex situ and in situ applications. Lately, the study sheds light on the manipulation of microorganisms through genetic engineering and nanotechnology for their advanced treatment approaches.
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Alteration of enzyme activities and functional diversity of a soil contaminated with copper and arsenic.
Aponte, H, Herrera, W, Cameron, C, Black, H, Meier, S, Paolini, J, Tapia, Y, Cornejo, P
Ecotoxicology and environmental safety. 2020;:110264
Abstract
Copper (Cu) mining has to address a critical environmental issue related to the disposal of heavy metals and metalloids (HMs). Due to their deleterious effects on living organisms, Cu and arsenic (As) have gained global attention, and thus their monitoring in the environment is an important task. The aims of this study were: 1) to evaluate the alteration of soil enzyme activities (EAs) and soil microbial functional diversity with Cu/As contamination, and 2) to select the most reliable biochemical indicators of Cu/As contamination. A twelve-week soil experiment was performed with four increasing levels of Cu, As, and Cu/As from 150/15 to 1000/100 mg Cu/As kg-1. Soil enzyme activities and soil community-level physiological profile (CLPP) using MicroResp™ were measured during the experiment. Results showed reduced EAs over time with increasing Cu and Cu/As levels. The most Cu-sensitive EAs were dehydrogenase, acid phosphatase, and arylsulfatase, while arginine ammonification might be related to the resilience of soil microbial communities due to its increased activity in the last experimental times. There was no consistent response to As contamination with reduced individual EAs at specific sampling times, being urease the only EA negatively affected by As. MicroResp™ showed reduced carbon (C) substrate utilization with increasing Cu levels indicating a community shift in C acquisition. These results support the use of specific EAs to assess the environmental impact of specific HMs, being also the first assessment of EAs and the use of CLPP (MicroResp™) to study the environmental impact in Cu/As contaminated soils.