Acute and chronic arsenic toxicity
TL;DR: There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven, and there is increasing emphasis on using alternative supplies of water.
Abstract: Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.
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TL;DR: Air pollution has both acute and chronic effects on human health, affecting a number of different systems and organs, and ranges from minor upper respiratory irritation to chronic respiratory and heart disease, lung cancer, acute respiratory infections in children and chronic bronchitis in adults.
3,000 citations
Cites background from "Acute and chronic arsenic toxicity"
...Neurotoxicity leading to neuropathies, with symptoms such as memory disturbances, sleep disorders, anger, fatigue, hand tremors, blurred vision, and slurred speech, have been observed after arsenic, lead and mercury exposure (Ewan and Pamphlett, 1996; Ratnaike, 2003)....
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TL;DR: This paper provides a comprehensive ecological and health risk assessment on the heavy metals in soils in Chinese industrial and agricultural regions and thus provides insights for the policymakers regarding exposure reduction and management.
1,019 citations
01 Jan 2006-Journal of Environmental Science and Health Part A-toxic\/hazardous Substances & Environmental Engineering
TL;DR: Factors combining to increase/decrease the ill effects of As include duration and magnitude of As Exposure, source of As exposure, nutrition, age and general health status.
Abstract: The ill effects of human exposure to arsenic (As) have recently been reevaluated by government agencies around the world. This has lead to a lowering of As guidelines in drinking water, with Canada decreasing the maximum allowable level from 50 to 25 microg/L and the U.S. from 50 to 10 microg/L. Canada is currently contemplating a further decrease to 5 microg/L. The reason for these regulatory changes is the realization that As can cause deleterious effects at lower concentrations than was previously thought. There is a strong relationship between chronic ingestion of As and deleterious human health effects and here we provide an overview of some of the major effects documented in the scientific literature. As regulatory levels of As have been decreased, an increasing number of water supplies will now require removal of As before the water can be used for human consumption. While As exposure can occur from food, air and water, all major chronic As poisonings have stemmed from water and this is usually the predominant exposure route. Exposure to As leads to an accumulation of As in tissues such as skin, hair and nails, resulting in various clinical symptoms such as hyperpigmentation and keratosis. There is also an increased risk of skin, internal organ, and lung cancers. Cardiovascular disease and neuropathy have also been linked to As consumption. Verbal IQ and long term memory can also be affected, and As can suppress hormone regulation and hormone mediated gene transcription. Increases in fetal loss and premature delivery, and decreased birth weights of infants, can occur even at low (<10 microg/L) exposure levels. Malnourished people have been shown to be more predisposed to As-related skin lesions. A large percentage of the population (30-40%) that is using As-contaminated drinking water can have elevated As levels in urine, hair and nails, while showing no noticeable clinical symptoms, such as skin lesions. It is therefore important to carry out clinical tests of As exposure. Factors combining to increase/decrease the ill effects of As include duration and magnitude of As exposure, source of As exposure, nutrition, age and general health status. Analytical determinations of As poisoning can be made by examining As levels in urine, hair and toenails. Communities and individuals relying on groundwater sources for drinking water need to measure As levels to ensure that their supplies are safe. Communities with water As levels greater than 5 microg/L should consider a program to document As levels in the population.
795 citations
Cites background from "Acute and chronic arsenic toxicity"
...[7] Several review articles have also been published, including Yoshida et al.,[8] Luster and Simeonova,[9] Watanabe,[10] Tchounwou et al.,[11] Rossman et al.,[12] Mahata et al.,[13] Kitchin,[14] and Ratnaike....
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...Social Impact of Chronic Arsenic Exposure and Safety Caution In their review of chronic As toxicity, Ratnaike et al.[15] stressed the impact of As contamination, not only on people’s health, but also on the economy, personal incomes and crop productivity....
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...,[13] Kitchin,[14] and Ratnaike.[15] Throughout this review it is important to mention that, whenever not stated otherwise, “arsenic” means total inorganic As....
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TL;DR: The effects of arsenic on the human body with a main focus on assorted organ systems with respective disease conditions are outlined and underlying mechanisms of disease development in each organ system due to arsenic have been explored.
601 citations
TL;DR: Although the adverse health effects arising from exposure to arsenic have been well-recognized, the mechanism(s) of action responsible for the diverse range of health effects are complicated and poorly understood.
Abstract: Arsenic is a trace element found in the earth’s crust at an average concentration of ∼5 μg/g (ppm). Although its relative abundance in the earth’s crust is about 54th, arsenic can become concentrated in some parts of the world because of natural mineralization. Arsenic is a component of 245 minerals, associated most frequently with other metals such as copper, gold, lead, and zinc in sulfidic ores.1−3 When disturbed by natural processes, such as weathering, biological activity, and volcanic eruption, arsenic may be released into the environment. Anthropogenic activities, such as combustion of fossil fuels, mining, ore smelting, and well drilling, also mobilize and introduce arsenic into the environment.
Chronic exposure to arsenic from groundwater has been recognized to cause the largest environmental health disaster in the world, putting more than 100 million people at risk of cancer and other arsenic-related diseases.4,5 Because of its prevalence in the environment, potential for human exposure, and the magnitude and severity of health problems it causes, the United States Agency for Toxic Substances and Disease Registry (ATSDR) has ranked arsenic as No. 1 on its Priority List of Hazardous Substances for many years. The recent priority list, posted in 2011 (http://www.atsdr.cdc.gov/SPL/index.html), shows arsenic as No. 1, ahead of lead, mercury, and polychlorinated biphenyls (PCBs).
Epidemiological studies of populations exposed to high levels of arsenic due to ingestion from water, including those from Taiwan,6−8 Argentina,9,10 Chile,11,12 West Bengal, India,13,14 Bangladesh,15−17 and Inner Mongolia, China,18,19 have repeatedly shown strong associations between the exposure to high concentrations of arsenic and the prevalence of several cancers,20−23 most severely bladder, lung, and skin cancers. Arsenic is classified as a human carcinogen by the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (EPA). Chronic exposure to elevated concentrations of arsenic has also been associated with the increased risk of a number of noncancerous effects.24−27 Although the adverse health effects arising from exposure to arsenic have been well-recognized, the mechanism(s) of action responsible for the diverse range of health effects are complicated and poorly understood.26−30
It is believed that inorganic arsenate (HAsO42-), which is a molecular analogue of phosphate (HPO42-), can compete for phosphate anion transporters and replace phosphate in some biochemical reactions.28 For example, generation of adenosine-5′-triphosphate (ATP) during oxidative phosphorylation can be inhibited by the replacement of phosphate with arsenate. Depletion of ATP by arsenate has been observed in cellular systems.28 However, the replacement of phosphate in DNA by arsenic is not firmly established.31−35
The toxicity of trivalent arsenicals likely occurs through the interaction of trivalent arsenic species with sulfhydryl groups in proteins. Arsenic binding to a specific protein could alter the conformation and function of the protein as well as its recruitment of and interaction with other functional proteins. Therefore, there has been much emphasis on studies of arsenic binding to proteins, for the purpose of understanding arsenic toxicity and developing arsenic-based therapeutics.
This review summarizes various aspects of arsenic binding to proteins. It discusses the chemical basis and biological implications and consequences of arsenic binding to proteins. It also describes analytical techniques and the characterization of arsenic binding, including the binding affinity, kinetics, and speciation.
591 citations
References
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TL;DR: The identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei is reported, indicating that AIF is a mitochondrial effector of apoptotic cell death.
Abstract: Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis. Here we report the identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei. AIF is a flavoprotein of relative molecular mass 57,000 which shares homology with the bacterial oxidoreductases; it is normally confined to mitochondria but translocates to the nucleus when apoptosis is induced. Recombinant AIF causes chromatin condensation in isolated nuclei and large-scale fragmentation of DNA. It induces purified mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Microinjection of AIF into the cytoplasm of intact cells induces condensation of chromatin, dissipation of the mitochondrial transmembrane potential, and exposure of phosphatidylserine in the plasma membrane. None of these effects is prevented by the wide-ranging caspase inhibitor known as Z-VAD.fmk. Overexpression of Bcl-2, which controls the opening of mitochondrial permeability transition pores, prevents the release of AIF from the mitochondrion but does not affect its apoptogenic activity. These results indicate that AIF is a mitochondrial effector of apoptotic cell death.
4,095 citations
TL;DR: Sedimentological study of the Ganges alluvial sediments shows that the arsenic derives from the reductive dissolution of arsenic-rich iron oxyhydroxides, which in turn are derived from weathering of base-metal sulphides.
Abstract: In Bangladesh and West Bengal, alluvial Ganges aquifers used for public water supply are polluted with naturally occurring arsenic, which adversely affects the health of millions of people. Here we show that the arsenic derives from the reductive dissolution of arsenic-rich iron oxyhydroxides, which in turn are derived from weathering of base-metal sulphides. This finding means it should now be possible, by sedimentological study of the Ganges alluvial sediments, to guide the placement of new water wells so they will be free of arsenic.
1,454 citations
TL;DR: As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy, and Pharmacokinetic studies showed that after a peak level of 5.54 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O2 did not alter its pharmacokinetic behaviors.
1,398 citations
TL;DR: Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed and the clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.
Abstract: Background Two reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action. Methods Twelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for PML–RAR-α fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3. Results Of the 12 patients studied, 11 had a complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 515 mg). Adverse effects were relatively m...
1,210 citations
TL;DR: An attempt is made to quantify the global element cycle for arsenic, based on an extensive literature research with special emphasis on the most recent works.
812 citations