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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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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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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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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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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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Developmental toxicity of arsenic: a drift from the classical dose-response relationship.
Bjørklund, G, Tippairote, T, Rahaman, MS, Aaseth, J
Archives of toxicology. 2020;(1):67-75
Abstract
Arsenic is a well-known natural environmental contaminant distributed in food, water, air, and soil. The developmental toxicity of arsenic exposure is a significant concern in large parts of the world. Unlike acute toxic exposure, the classical dose-response relationship is not adequate for estimating the possible impact of chronic low-level arsenic exposure. The real-life risk and impact assessments require the consideration of the co-exposure to multiple toxins, individual genetic and nutritional predisposition, and the particularly vulnerable stages of the neurodevelopment. This context shifts the assessment model away from the 'one-exposure-for-one-health-effect.' We underscore the need for a comprehensive risk assessment that takes into account all relevant determinants. We aim to elaborate a model that can serve as a basis for an understanding of complex interacting factors in a long-lasting and ongoing low-level arsenic exposure, to identify, protect, and support the children at risk.
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Heavy metals in food crops: Health risks, fate, mechanisms, and management.
Rai, PK, Lee, SS, Zhang, M, Tsang, YF, Kim, KH
Environment international. 2019;:365-385
Abstract
Food security is a high-priority issue for sustainable global development both quantitatively and qualitatively. In recent decades, adverse effects of unexpected contaminants on crop quality have threatened both food security and human health. Heavy metals and metalloids (e.g., Hg, As, Pb, Cd, and Cr) can disturb human metabolomics, contributing to morbidity and even mortality. Therefore, this review focuses on and describes heavy metal contamination in soil-food crop subsystems with respect to human health risks. It also explores the possible geographical pathways of heavy metals in such subsystems. In-depth discussion is further offered on physiological/molecular translocation mechanisms involved in the uptake of metallic contaminants inside food crops. Finally, management strategies are proposed to regain sustainability in soil-food subsystems.
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On the Use of Hair Analysis for Assessing Arsenic Intoxication.
Katz, SA
International journal of environmental research and public health. 2019;(6)
Abstract
Correlations between the concentrations of arsenic in scalp hair and in drinking water as well as in blood and/or urine have been reported. These correlations clearly show exposure⁻absorption⁻excretion relationships. In addition, arsenic metabolites such as monomethylarsonic acid and dimethylarsinic acid have been identified and quantified in these tissues and fluids, leaving little doubt that elevated levels of arsenic in the hair can reflect systemic arsenic intoxication. Consequently, hair analysis has potential merit as a screening procedure for poisoning by arsenic. However, questions regarding the exogenous versus the endogenous deposition of arsenic in the hair, and uncertainties about the normal level of arsenic in the hair remain unresolved. Pending their resolution, the determination of arsenic in hair should remain a screening tool, and clinical signs and symptoms should be employed to complete the diagnosis of arsenic poisoning.
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Groundwater Arsenic Contamination in the Ganga River Basin: A Future Health Danger.
Chakraborti, D, Singh, SK, Rahman, MM, Dutta, RN, Mukherjee, SC, Pati, S, Kar, PB
International journal of environmental research and public health. 2018;(2)
Abstract
This study highlights the severity of arsenic contamination in the Ganga River basin (GRB), which encompasses significant geographic portions of India, Bangladesh, Nepal, and Tibet. The entire GRB experiences elevated levels of arsenic in the groundwater (up to 4730 µg/L), irrigation water (~1000 µg/L), and in food materials (up to 3947 µg/kg), all exceeding the World Health Organization's standards for drinking water, the United Nations Food and Agricultural Organization's standard for irrigation water (100 µg/L), and the Chinese Ministry of Health's standard for food in South Asia (0.15 mg/kg), respectively. Several individuals demonstrated dermal, neurological, reproductive, cognitive, and cancerous effects; many children have been diagnosed with a range of arsenicosis symptoms, and numerous arsenic-induced deaths of youthful victims are reported in the GRB. Victims of arsenic exposure face critical social challenges in the form of social isolation and hatred by their respective communities. Reluctance to establish arsenic standards and unsustainable arsenic mitigation programs have aggravated the arsenic calamity in the GRB and put millions of lives in danger. This alarming situation resembles a ticking time bomb. We feel that after 29 years of arsenic research in the GRB, we have seen the tip of the iceberg with respect to the actual magnitude of the catastrophe; thus, a reduced arsenic standard for drinking water, testing all available drinking water sources, and sustainable and cost-effective arsenic mitigation programs that include the participation of the people are urgently needed.