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Arsenic contamination has long been recognized as one of the most harmful environmental pollutants resulting from anthropogenic activity. Apart from being an environmental toxicant or pollutant, this culpable heavy metal also has detrimental effects on human health. People throughout the world are exposed to arsenic (As) mostly through polluted drinking water. Acute inorganic arsenic (iAs) poisoning causes nausea, vomiting, stomach discomfort, and severe diarrhea. As on long-term exposure is a potent carcinogen, characterized by IARC (International Agency for Research on Cancer). As levels are high mainly in Gangetic regions due to which the people living around are suffering the consequences. The carcinogenicity of As is well established but the immunotoxicity caused by it is still unknown. Some animal model supports the toxicity of As in the immune system as well, but in humans, mainly suffering from human immunodeficiency virus (HIV), it is not well established. iAs suppresses the immune system by acting on different targets and exacerbating infections. Although animal studies have demonstrated that arsenic trioxide (As

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders.

The prime objective of the present study was to establish fenugreek (Trigonella foenum-graecum L.) seeds extract as an antidote against arsenic induced hepato-renal toxicity in rats. The male Charles Foster rats (weighing 160-180 g) were selected to make arsenic intoxicated model. The arsenic treated group of rats were orally treated with sodium arsenite at the dose of 8 mg/kg body weight/day for 90 days. Thereafter, the arsenic pretreated rats were further administered with fenugreek ethanolic seeds extract at the dose of 250 mg/kg body weight/day for 90 days. After the completion of the treatment, animals of all the groups were sacrificed for the biochemical and histopathological estimation. The arsenic treated rats showed significant (p < 0.0001) alterations at the various hepatic and renal biomarker parameters and at serum MDA levels in comparison to the control rats. Significant (p < 0.0001) arsenic accumulation was also observed in the blood, liver and kidney tissues of the arsenic treated rats. However, after the administration with fenugreek seeds extract, significant (p < 0.0001) restoration was observed in the liver and kidney biomarker parameters and at haematological variables. Fenugreek seeds extract administration also significantly (p < 0.0001) reduced the serum MDA levels and arsenic concentration levels in blood, liver and kidney tissues, along with considerable restorations at the cellular architecture of liver and kidney tissues. The study concluded that fenugreek seeds possessed potential hepato-renal ameliorative effect against sodium arsenite induced toxicity in rats, and can be used for its therapeutic value against arsenic poisoning.

Background:Sputum cytologic atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk.Methods:An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and 7 annual screenings since enrollment. The associations between sputum cytologic results from baseline screening, the first 4 consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model.Results:A moderate or worse cytologic result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared with negative screening results, the adjusted hazard ratios of baseline-moderate or worse atypia, at least one moderate or worse atypia in the first 4 consecutive screening rounds during the first 10 years of follow-up were 3.11 [95% confidence interval (CI): 2.37–4.07], 3.25 (95% CI: 2.33–4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio = 17.55, 95% CI: 8.32–37.03); atypia identified in the recent screening rounds (adjusted HR = 4.14, 95% CI: 2.70–6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer.Conclusions:Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years.Impact:Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance, or chemoprevention of lung cancer.

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.

Increasing evidence supports the role of arsenic in dysregulated immune and inflammation responses, while, safe and effective treatments have not been fully examined.

Diagnosing heavy metals poisoning in human beings is of paramount importance. In this work, we present the design of a biocompatible Fe

Several lines of evidence support a significant relationship between exposure to arsenic and diabetes. However, the underlying pathophysiological mechanisms remain incompletely elucidated.This study examined the association and risk of circulating inflammatory mediators with hyperglycemia in coal-induced arsenicosis.A cross-sectional study was conducted in the typical coal-burning area in which arsenicosis is endemic in Xingren County, Guizhou, China. A total of 299 arsenicosis subjects and 137 non-arsenic exposed volunteers were recruited for the present study. Participant's hyperglycemia-related parameters, including fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment for both insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β), as well as circulating inflammatory biomarkers i.e., Interleukins-1β (IL-1β), IL- 2, IL - 6, IL-10, IL- 17, IL-18 and TNF-α), were determined and analyzed after completing questionnaire investigation and physical examination.The results clearly showed that coal-burning arsenic exposure was significantly associated with hyperglycemia-related outcomes. Specifically, arsenicosis subjects from the coal-burning endemic area showed a higher level of FBG (median 5.87 mmol/L vs. 4.65 mmol/L) and increased prevalence of hyperglycemia (26.76% vs.16.79%) than reference subjects from the non-arsenic endemic area. Increased HOMA-IR (median 1.93 vs.1.44) and declined HOMA-β (median 96.23 vs. 84.91) were also noted in arsenicosis subjects. Moreover, arsenic exposure was significantly associated with the increased risk of hyperglycemia (adjusted OR = 2.32, 95% CI: 1.37,3.93). In addition, a positive association between arsenic exposure and inflammatory response was observed, and the alteration in circulating inflammatory markers were found to be significantly associated with hyperglycemia-related parameters. Meanwhile, there was a positive relationship between elevated circulating IL-1β, IL-18, IL-6, as well as decreased IL-10 and the increasing risk of arsenic-induced hyperglycemia [adjusted OR = 2.19 (95% CI: 1.26, 3.13);1.13 (95%CI: 1.08, 1.37); 1.19 (95% CI: 1.13, 1.56); 1.15(95% CI: 1.05, 1.36); respectively]. Path analysis further revealed that the mediating effect of IL-1β and IL-18 on the relationship between arsenic exposure and hyperglycemia was closely associated with pancreatic β-cell dysfunction, while those of IL-6 and IL-10 on the association between arsenic exposure and hyperglycemia were partially through insulin resistance.This population-based study indicated that arsenic exposure has a clear disruptive effect on glucose homeostasis, and an elevated inflammatory response was implicated in the risk of arsenic-induced hyperglycemia.

Studies have demonstrated that arsenic (As) induces male reproductive injury, however, the mechanism remains unknown. The high levels of arsenic (3) methyltransferase (As3MT) promote As-induced male reproductive toxicity. For As-exposed mice, the germ cells in seminiferous tubules and sperm quality were reduced. Exposure to As caused lower S-adenosylmethionine (SAM) and 5-methylcytosine (5 mC) levels, histone and DNA hypomethylation, upregulation of long interspersed element class 1 (LINE1, or L1), defective repair of double-strand breaks (DSBs), and the arrest of meiosis, resulting in apoptosis of germ cells and lower litter size. For GC-2spd (GC-2) cells, As induced apoptosis, which was prevented by adding SAM or by reducing the expression of As3MT. The levels of LINE1, affected by SAM content, were involved in As-induced apoptosis. Furthermore, folic acid (FA) and vitamin B12 (VB

Elevated concentrations of total arsenic (As) have been reported in boreal freshwater fish in both human-impacted and relatively pristine areas. We assessed the arsenic speciation profiles in muscle tissue of six fish species (n = 300) sampled from nine locations across a remote freshwater watershed in northern Ontario, Canada, extending from inland headwater lakes to the coastal marine confluence. Of the five arsenic species measured, only arsenobetaine (AsB) and dimethylarsinic acid (DMA) were detected in these fish. Riverine fish had up to 10-fold higher total [As] when compared to lacustrine fish. On average, these riverine fish also had higher percentages of AsB (%AsB, 60 ± 26%) and lower percentages of unmeasured arsenic (%UNM, 20 ± 21%), compared to lacustrine fish (28 ± 18% and 52 ± 21% %AsB and %UNM, respectively). DMA percentages (%DMA) were relatively consistent across the watershed, averaging 20 ± 21% across all fish. We examined ecological drivers of As speciation and found that %AsB increased slightly with fish weight in large-body predatory fish, but not in forage fish or insectivores. Furthermore, %AsB was positively related to trophic elevation (inferred from δ

Arsenic is a naturally occurring element in the earth's crust. Chronic arsenic poisoning has been regularly reported predominantly due to occupational exposure in the literature. Acute arsenic poisoning is very rare. A 27-year-old gentleman was brought to the hospital with a history of suicide attempt by consumption of arsenic trioxide diluted in water. He initially manifested with gastrointestinal manifestations along with tachycardia. The patient was treated with fluid resuscitation, antidote-Dimercaprol, dialysis, and other supportive treatment. The patient continued to deteriorate with deranged liver and renal function, coagulopathy, and neurological symptoms. The presence of coagulopathy further complicated the scenario, as the antidote which is administered as an intramuscular injection could not be given. The patient continued to deteriorate and eventually succumbed. Acute arsenic poisoning is very rare, and very few reports of suicide are reported. It initially presents with acute gastroenteritis symptoms followed by multi organ involvement. Fatal doses will invariably result in death irrespective of treatment modality. Rapid administration of antidote and supportive treatment might increase the chances of survival. Difficulty in the availability of oral antidote and unavailability of any Intravenous preparations further complicates the scenario.

Arsenic is a naturally occurring environmental toxicant, chronic exposure to arsenic can cause multiorgan damage, except for typical skin lesions, liver damage is the main problem for health concern in population with arsenic poisoning. Abnormal apoptosis is closely related to liver-related diseases, and p53 is one of the important hallmark proteins in apoptosis progression. This study was to investigate whether arsenic poisoning-induced hepatocyte apoptosis and the underlying role of p53 signaling pathway. A rat model of arsenic poisoning was established by feeding corn powder for 90 days, which was baked with high arsenic coal, then were treated with Ginkgo biloba extract (GBE) for 45 days by gavage. The results showed that arsenic induced liver damage, increased hepatocyte apoptosis and elevated the expression level of Chk1 and the ratios of p-p53/p53 and Bax/Bcl-2 in liver tissues, which were significantly attenuated by GBE. Additionally, to further demonstrate the potential apoptosis-associated mechanism, L-02 cells were pre-incubated with p53 inhibitor pifithrin-α (PFTα), ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor (CGK733) or GBE, then treated with sodium arsenite (NaAsO2) for 24 h. The results showed that GBE, PFTα or CGK733 significantly reduced arsenic-induced Chk1 expression and the ratios of p-p53/p53 and Bax/Bcl-2. In conclusion, Chk1-p53 pathway was involved in arsenic poisoning-induced hepatotoxicity, and inhibiting of Chk1-p53 pathway ameliorated hepatocyte apoptosis caused by coal-burning arsenic poisoning. The study provides a pivotal clue for understanding of the mechanism of arsenic poisoning-induced liver damage, and possible intervention strategies.

The present study aims to estimate geochemical arsenic toxicity in the domestic livestock and possible risk for human and environment caused by them. Daily dietary arsenic intake of an exposed adult cow or bull is nearly 4.56 times higher than control populace and about 3.65 times higher than exposed goats. Arsenic toxicity is well exhibited in all the biomarkers through different statistical interpretations. Arsenic bioconcentration is faster through water compared to paddy straw and mostly manifested in faeces and tail hair in cattle. Cow dung and tail hair are the most pronounced pathways of arsenic biotransformation into environment. A considerable amount of arsenic has been observed in animal proteins such as cow milk, boiled egg yolk, albumen, liver and meat from the exposed livestock. Cow milk arsenic is mostly accumulated in casein (83%) due to the presence of phosphoserine units. SAMOE–risk thermometer, calculated for the most regularly consumed foodstuffs in the area, shows the human health risk in a distinct order: drinking water > rice grain > cow milk > chicken > egg > mutton ranging from class 5 to 1. USEPA health risk assessment model reveals more risk in adults than in children, subsisting severe cancer risk from the foodstuffs where the edible animal proteins cannot be ignored. Therefore, the domestic livestock should be urgently treated with surface water, while provision of both arsenic-free drinking water and nutritional supplements is mandatory for the affected human population to overcome the severe arsenic crisis situation.

Chronic arsenism usually occurs after a long-term unawareness of arsenic exposure from environment, occupation, food, and water. We here reported 3 cases with diffused arsenic keratosis and skin cancers derived from long-term arsenic medication ingestion. In these cases, hyperkeratotic skin lesions were initially found on palms and soles, slowly progressed to every part of the skin and lasted maximally for over 30 years. Skin cancers were diagnosed and removed intermittently within decades, but with no malignancies in other organs. Oral retinoids combing with topical 5- fluorouracil and photodynamic treatment yielded a desirable outcome.

Graphical abstract, Highlights • Sodium arsenite disrupts the histoarchitecture and cell morphology causing cell death in thymus and spleen of Swiss albino mice. • Activation of apoptotic cell death occurred due to high level of ROS generation and increased promotion of autophagy upon arsenic insult. • SNEC30 restored cellular architecture, reduced ROS generation and ameliorated autophagy-mediated cell death in the immune organs. • This study clearly demonstrated anti-oxidative and anti-apoptotic properties of SNEC30 against NaAsO2-induced in vivo immunotoxicity., Several precedents have confirmed numerous infirmities caused by arsenic poisoning, including immune suppression and cancer. Exposure to arsenic leads to alterations of the cellular machinery and eventually cell death, depending on the dose and duration of exposure. Oxidative stress induced by arsenic is the major mechanism by which it inflicts cellular toxicity, challenging the survival-support - autophagy and culminating in apoptosis in the thymus and spleen of mice. Curcumin, a potent dietary anti-oxidant with known anti-apoptotic and anti-inflammatory properties, was assessed for therapeutic benefits. However, the major caveat of this polyphenol is its low water solubility and limited bioavailability. Therefore, Self Nano-Emulsifying Curcumin (SNEC30) was used to treat mice exposed to arsenic. When administered, SNEC30 effectively ameliorated the adverse effects of arsenic in mice, by restoring structural alterations and reducing ROS-mediated cell death, thereby endorsing the importance of nutraceuticals in counteracting heavy metal-induced cellular toxicity.

During the late nineteenth and early twentieth centuries, arsenic was used as an embalming agent in the United States. In 1996, Konefes and McGee brought the potential danger of arsenic poisoning during excavation to the attention of archaeologists. They developed methodology that was later refined by the present authors. This article discusses the history of arsenic as an embalming agent, explores socioeconomic and demographic factors that might suggest the presence of arsenic in certain burials, and presents methods for testing arsenic in archaeological contexts. We also discuss environmental impact mitigation considerations and review examples of arsenic testing in archaeological contexts.

Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning ( Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.砷是一种非金属元素，国际癌症研究机构已经明确砷及其化合物是致癌物质。砷及其化合物可经呼吸道、皮肤和消化道吸收，分布于肝、肾、肺以及皮肤中，并对其造成损伤。而非编码RNA与砷所致神经系统紊乱、细胞坏死、生殖毒性和癌变等密切相关。近年来，非编码RNA中的微小RNA（miRNAs）、长链非编码RNA（lncRNAs）和环状RNA（circRNAs）在砷诱导的各种疾病中的网络调控已成为新的研究领域。本文通过总结已有的科研成果，对miRNAs、lncRNAs和circRNAs在砷毒性中的作用机制进行阐述，为砷中毒的防治提供基础资料和理论依据。.

A positive answer to this topic was given in 1882 by prof. N. M. Popov in his dissertation: "Materials for science on acute mellitic toxic origin". He asserts that, first of all, the nerve cells (of the spinal cord) come to a state of turbid swelling and vacuolization. Both of these processes can lead them to complete destruction: the first, through the transition to a bland, spreading formation, the second, through an increase in the vacuole. Finally, in the late period, there is a pigment atrophy, which destroys all the cells, the improvement from the previous changes. The intensity of the process is determined by the greater or lesser proximity of the vessel .... In all likelihood, the author says, the brain also changes here. With the same positivity, the suffering of the peripheral nervous system is excluded in this work.

Arsenic is a grey substance, which is insoluble in water and therefore cannot be absorbed from the alimentary canal. Arsenic is absorbed through all routes mainly by skin, inhalation and GIT mucosa. Arsenic causes toxicity by combining with sulphydryl enzymes and thus interfering with cell metabolism. Locally it causes irritation of the mucous membranes and remotely depression of the nervous system. Arsenic poisoning can be homicidal, suicidal, accidental, occupational, environmental, iatrogenic or un-iatrogenic. The character of post-mortem appearances depends very largely upon the quantity taken and period which has elapsed before death. Externally the body presents dehydrated, cyanosed, sunken eyeballs jaundiced in post-mortem findings. Rigor mortis lasts longer than usual. Internally red velvet stomach, petechial hemorrhages under the endocardium of the left ventricle, patchy fatty degenerative changes with jaundice in liver, rain drop skin pigmentation and mee’s line in nails findings seen in post-mortem.

Arsenic trioxide (ATO) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (CRT), the critical ingredient of saffron. Sprague‑Dawley rats were then randomly divided into four groups (n=10/group): i) Control group; ii) ATO group, iii) CRT‑low (20 mg/kg) group; and iv) CRT‑high (40 mg/kg) group. Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and CRT groups were administered with either 20 and 40 mg/kg CRT. Following 6 h, all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days. Cardiotoxicity was indicated by changes in electrocardiographic (ECG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis‑related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. Cardiotoxicity was induced in male Sprague‑Dawley rats with ATO (5 mg/kg). CRT (20 and 40 mg/kg) and ATO were co‑administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J‑point elevation induced by ATO in rats. Histological changes were evaluated via hematoxylin and eosin staining. CRT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione‑peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, CRT downregulated the expression levels of the pro‑inflammatory factors IL‑1, TNF‑α, IL‑6, Bax and p65, as well as increased the expression of Bcl‑2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that CRT treatment effectively ameliorated ATO‑induced cardiotoxicity. The protective effects of CRT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment, and additional clinical applications are possible, but warrant further investigation.

Arsenic poisoning is one of the most serious health hazards of recent times. It has been estimated that more than 200 million people of about 105 countries in the world are affected due to arsenic poisoning. Except mitigation, there is no such mode by which the population can be prevented from being exposed to arsenic. Tinospora cordifolia (T. cordifolia) is widely used in the folk medicine system for the treatment of various diseases. Hence, the aim of the present study was to investigate the antidote effects of ethanolic extract of T. cordifolia stem against arsenic induced hepato-renal toxicity in rat model. Twenty-four male Charles Foster rats (weighing 160–180 g) were randomly divided into two groups, where six rats were used as control group. Eighteen rats were orally treated with arsenic at the dose of 8 mg/kg body weight for 90 days daily and then further divided into three sub groups (n = 6 each). Sub group I—arsenic treated rats, were sacrificed after treatment; sub group II rats were used as arsenic control and the sub group III rats were administrated with T. cordifolia at the dose of 400 mg/kg body weight/day for 90 days. After the completion of dose duration, all the control and treatment group rats were sacrificed to evaluate the various parameters. Arsenic induced rats had significantly (p

In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic‐contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants. In total, 6223 survivors (mean age at enrollment, 27.5 y) who had ingested contaminated milk when they were aged ≤ 2 y participated in this study. Follow‐up was conducted from 1982 to 2018 (mean follow‐up duration, 30.3 y). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality and cancer incidence rates of subjects with the respective Japanese population rates, and 95% confidence intervals (95% CIs) of the SMR and SIR were also calculated. In total, 561 deaths and 524 new cancer cases were observed. A statistically significant increase in mortality rate was observed for all causes (SMR, 1.15; 1.01‐1.19), nervous system disease (2.83, 1.62‐4.19), respiratory disease (2.02, 1.37‐2.62), genitourinary system disease (2.25, 1.10‐3.73), and traffic accident (2.03, 1.14‐3.04). In contrast, a significant decrease in cancer incidence rate was observed for all cancers (SIR, 0.96; 0.84‐0.99), stomach cancer (0.77, 0.57‐0.92), colon cancer (0.63, 0.41‐0.85), rectum cancer (0.69, 0.43‐0.95), and breast cancer (0.72, 0.52‐0.89). Liver cancer showed a high mortality rate (SMR, 1.68; 1.06‐2.31). In this study, after the long‐term follow‐up we revealed overall and cause‐specific mortality and cancer incidence risk among survivors who ingested arsenic‐contaminated dry milk as infants., In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic‐contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants.

The World Health Organization has labeled the problem of arsenic contamination of groundwater in South Asia as “the largest mass poisoning in human history.” Various technical solutions to the problem fall into one of two broad categories: (i) cleaning contaminated water before human consumption and (ii) encouraging people to switch to less contaminated water sources. In this paper, we review research on the behavioral, social, political, and economic factors that determine the field-level effectiveness of the suite of technical solutions and the complexities that arise when scaling such solutions to reach large numbers of people. We highlight the conceptual links between arsenic-mitigation policy interventions and other development projects in Bangladesh and elsewhere, as analyzed by development economists, that can shed light on the key social and behavioral mechanisms at play. We conclude by identifying the most promising policy interventions to counter the arsenic crisis in Bangladesh. We support a national well-testing program combined with interventions that address the key market failures (affordability, coordination failures, and elite and political capture of public funds) that currently prevent more deep-well construction in Bangladesh.

The value of the glutathione S-transferase (GST) null genotype in patients with arsenic poisoning has been recognized, but the conclusions of previous studies remain inconsistent. The objective of this study was to evaluate the relationship between GST mu 1 (GSTM1) and GST theta 1 (GSTT1) null genotype polymorphisms and susceptibility to arsenic poisoning. PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and WeiPu databases were systematically searched for publications up to March 31, 2020. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to estimate the relationship between GSTM1 and GSTT1 null genotype polymorphisms and arsenic poisoning. The meta-analysis was conducted using STATA 14.0 software. Nine articles with 3324 subjects were included in the meta-analysis. A significantly negative correlation was observed between the GSTM1 null genotype and susceptibility to arsenic poisoning (OR = 0.731; 95% CI: 0.536-0.999; P = 0.049; I2 = 70.5%). There was no significant correlation between the GSTT1 null genotype (OR = 1.009; 95% CI: 0.856-1.189; P = 0.915, I2 = 36.8%) and GSTM1-GSTT1 double null genotype (OR = 1.105; 95% CI: 0.670-1.822; P = 0.695; I2 = 64.7%) and the risk of arsenic poisoning. Egger's and Begg's tests indicated no publishing bias. Compared with controls, individuals with the GSTM1 null genotype were less susceptible to arsenic poisoning. The GSTT1 single null genotype and GSTM1-GSTT1 dual-null genotype were not associated with the risk of arsenic poisoning. The GSTM1 single null genotype may have potential as a genotoxic biomarker to identify individuals who are not prone to arsenic poisoning, and as a reference for guiding the prevention of arsenic poisoning.

Arsenic in the present times has caused lots of health hazards to humans. In developing countries like Bangladesh and India the high prevalence of contamination, the isolation and poverty of the rural population, and the high cost and complexity of arsenic removal systems have imposed a programmatic and policy challenge on an unprecedented scale. Although in India, arsenic poisoning in ground water in Gangetic belt especially the districts adjoining the river Ganges right from Eastern Uttar Pradesh, Bihar to West Bengal. These regions are the problem of concern as due to which major health related problems are arising. To combat the present problem, a pre-clinical study was carried out on Charles foster rats. They were treated with Sodium arsenite at the dose of 8 mg per kg body weight for 16 weeks to make arsenic model and upon these arsenic pre-treated rats seed extracts of Piper nigrum at the dose of 50 mg per kg body weight was administered for 4 weeks to study the antidote effects of this plant extract. The Piper nigrum extract not only eliminated the effects of arsenic but also reversed the normal physiological activity in the animal by normalising the activity of liver and kidney. The present study concludes that this novel plant extract possesses hepato-protective as well as nephro-protective activity against arsenic induced toxicity.

Long-term arsenic exposure is a worldwide public health problem that causes serious harm to human health. The liver is the main target organ of arsenic toxicity; arsenic induces disruption of the DNA damage repair pathway, but its mechanisms remain unclear. In recent years, studies have found that epigenetic mechanisms play an important role in arsenic-induced lesions. In this study, we conducted experiments in vitro using normal human liver cells (L-02) to explore the mechanism by which the histone demethylase JHDM2A regulates H3K9 dimethylation (me2) in response to arsenic-induced DNA damage. Our results indicated that arsenic exposure upregulated the expression of JHDM2A, downregulated global H3K9me2 modification levels, increased the H3K9me2 levels at the promoters of base excision repair (BER) genes (N-methylpurine-DNA glycosylase [MPG], XRCC1 and poly(ADP-ribose)polymerase 1) and inhibited their expression levels, causing DNA damage in cells. In addition, we studied the effects of overexpression and inhibition of JHDM2A and found that JHDM2A can participate in the molecular mechanism of arsenic-induced DNA damage via the BER pathway, which may not be involved in the BER process because H3K9me2 levels at the promoter region of the BER genes were unchanged following JHDM2A interference. These results suggest a potential mechanism by which JHDM2A can regulate the MPG and XRCC1 genes in the process of responding to DNA damage induced by arsenic exposure and can participate in the process of DNA damage repair, which provides a scientific basis for understanding the epigenetic mechanisms and treatments for endemic arsenic poisoning.

Chronic arsenic poisoning is one of the serious health hazards in West Bengal, India, and Bangladesh. It occurs due to contaminated subsoil water. The aim of this study is conducted to find out the ameliorative effect of turmeric and P. foetida powder on experimentally induced arsenic toxicity in sheep. Twelve sheep were divided into four groups; groups I, II and III were orally administered with sodium arsenite at 6.6 mg/kg body weight for 133 days; groups I and II animals were treated by turmeric and P. foetida powders respectively at 500 mg/kg dose for the last 49 days; the fourth group was control. Arsenic content was estimated in faeces, urine and wool in every 15 days. Biochemical, haematological, antioxidant parameters and DNA fragmentation were also assessed. Turmeric and P. foetida powder treatment significantly (P < 0.05) increased arsenic elimination through faeces, urine and wool. Haemoglobin content and TEC were decreased in groups I, II and III; however, these were improved significantly (P < 0.05) by turmeric and P. foetida powder treatment. Increased activity of AST, ALT, blood urea nitrogen and plasma creatinine were significantly (P < 0.05) decreased in groups I and II. The reduced SOD and catalase activity were significantly (P < 0.05) restored at the end of the experiment in turmeric and P. foetida-treated groups. The test drugs are found significantly effective not only to eliminate arsenic from the body but also give protection from possible damage caused by arsenic exposure in sheep.

Arsenic is known to be an important aetiological factor for the development of urinary bladder cancer. It is known to be found excessively in ground water in certain geographical areas, including West Bengal. We have studied patients with recurrent bladder cancer from different areas of this Indian state and correlated arsenic as a causative aetiological factor for development and aggressiveness of the biological behaviour of urinary cancer. We included 31 patients from various parts of West Bengal state with recurrent bladder cancer who were operated in our institute. Their clinical and residential data and their arsenic content of tumour tissue were measured. Statistical analysis was performed to test the association of tissue arsenic with clinicopathological features of recurrent disease. We found very high levels of arsenic in tumour tissue in all residents of the districts with high prevalence of arsenic in the drinking water. We also observed more aggressive clinicopathological progression and early recurrence in patients with high arsenic content. We conclude that arsenic is a causal factor in the clinicopathological progression of recurrent urinary bladder cancer. Measures to decrease the level of arsenic in drinking water should be taken as this may both improve clinicopathological outcomes in the recurrence of urinary bladder carcinoma, as well as reducing its overall incidence.

BACKGROUND AND OBJECTIVES The French national authority for health (Haute autorite de sante: HAS) and the French clinical toxicology society (Societe de toxicologie clinique: STC) received a formal request from the French ministry for heath to elaborate recommendations for the screening of environmental overexposure to inorganic arsenic (iAs), for the medical management of overexposed patients and for the medical surveillance of exposed population. To allow these recommendations, preliminary literature retrieval and analysis were performed for identifying validated indicators of both exposure and early effects of iAs and their levels in the general population living in France. METHODS Evaluations of inorganic arsenic toxicity conducted by national or international health agencies during the last 3 decades were all examined and analyzed. These evaluations were completed by literature retrieval through Medline and Scopus from January 2016 to December 2019. RESULTS AND CONCLUSIONS The best biomonitoring indicator for iAs exposure is the sum of urine iAs, monmomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) concentrations (SAs). The upper limit of confidence interval of the 95th percentile of the distribution of this parameter in the general adult population living in France is 10 μg/g of creatinine, and is recommended as the limit value for the definition of overexposure. In less than 12 year-old children specific limit values are required, but not yet available. In their absence, SAs should exceed both 10 μg/g creatinine and 11 μg/L to be considered as indicating a probable overexposure to iAs. There are no useful biological indicators of iAs early effects. Non carcinogenic skin effects of inorganic arsenic (hyperpigmentation and keratosis) should be considered as the earliest deleterious effects of repeated environmental iAs exposure.

Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with arsenic metabolites being implicated in the pathogenesis. In contrast, arsenic trioxide (As2O3) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAsIII) to promyelocytic leukemia (PML) protein is the proposed initial step. These findings on the two-edged sword characteristics of arsenic suggest that after entry into cells, arsenic reaches the nucleus and triggers various nuclear events. Arsenic is reduced, conjugated with glutathione, and methylated in the cytosol. These biotransformations, including the production of reactive metabolic intermediates, appear to determine the intracellular dynamics, target organs, and biological functions of arsenic.

A 70 year-old man presented with insidiously progressing central visual acuity loss in both eyes over several years. Objectively the only abnormality identified on the exam was questionable granularity in the fovea in each eye. Extensive work up which included neuro-imaging, screening blood work for toxic and nutritional causes of optic neuropathy as well as electroretinogram and fluorescein angiography to rule out subtle maculopathy was all unrevealing. When vision continued to deteriorate over the next several years investigations were repeated and again did not yield any positive results. Levels of heavy metals were then obtained after further progression of visual loss, revealing very high levels of arsenic. Subsequent investigations revealed that patient has been spending almost every weekend for the past 28 years alone at a remote country cottage where the sole supply of water was from the local well. He also recalled that 1.5 months after purchasing the cottage he developed hemorrhagic colitis requiring partial colectomy. The specimen from colectomy was located and total reflection x-ray fluorescence testing performed in a specialized lab revealed greatly increased level of arsenic particle in the colonic biopsy from 28 years ago. This case is a reminder that heavy metal toxicity should be considered in a differential diagnosis of patients with bilateral symmetric optic neuropathy.

Arsenic, a toxic component in coal-fired flue gas, is poisonous to the commercial selective catalytic reduction (SCR) denitrification catalysts. To unveil the arsenic poisoning mechanism on commerc...

Arsenic and fluoride are two natural components affecting human health. Long-term exposure to arsenic and fluoride, mainly through drinking water intake, can lead to arsenicosis and fluorosis. In this paper, we summarized the distribution and hydrochemical characteristics of high-arsenic and high-fluoride groundwater, and reviewed the arsenicosis and fluorosis distribution due to consumption of high-arsenic and high-fluoride groundwater in China. The results show that there are 20 major provinces//autonomous regions (about 60%) in China suffering from high-arsenic groundwater, and these high-arsenic groundwater provinces are mainly located in the fluvial/alluvial-lacustrine plains and basins located in arid/semi-arid regions and alluvial plains/basins and river deltas in humid/semi-humid regions. Drinking water arsenicosis has been found in 13 provinces/autonomous regions, with Shanxi and Inner Mongolia being the two most seriously affected areas. High-fluoride groundwater is widely distributed in north, northeast and northwest parts of China, occurring mainly in shallow groundwater. Fluorosis has been found in 29 provinces/autonomous regions. With the continuous implementation of water quality improvement projects, drinking water fluorosis and arsenic poisoning have been effectively controlled. However, the long-term maintenance and operation of the water quality improvement project need to be further strengthened.

Arsenic from environmental contamination is a risk factor for kidney disease, and the clinical use of arsenic also triggers a new concern that the potential kidney damage caused by exposure to clinical doses of arsenic trivalent. So far, the undergoing mechanisms contributing to arsenic nephrotoxicity mostly remain unclear, and universally accepted methods for preventing this complication are limited too. Ancient Chinese medical scientists recognized the toxicity of arsenic long ago, and there were some records of Chinese herbs against arsenic poisoning in ancient books of Chinese medicine. In the past decade, several herbal formulations, as well as some potentially active compounds extracted from Chinese herbs, have been employed to prevent arsenic nephrotoxicity both in vivo and in vitro and showed better therapeutic effects. The present paper thus summarizes and discusses these Chinese medicine methods in preventing such a public health problem. In addition, we call for large, well-designed, randomized, and controlled clinical trials to be performed to further assess the efficacy and safety of these potential methods of Chinese medicine against arsenic nephrotoxicity.

Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of Ginkgo biloba extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro- and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro- and anti-inflammatory T cell balance.

Exposure to arsenic (As) mainly through contaminated drinking water enhances the lung tumor progression, invasion, and metastasis. The carcinogenic effect of As is due to the generation of reactive oxygen species (ROS) and DNA damage, and interference with DNA repair machinery. Herein, we investigated the potential therapeutic function of quercetin on As-treated lung cancer cells. Quercetin is a natural product with antioxidative, anti-inflammatory, and antiproliferative properties. We showed that quercetin induced cell death in the As-exposed lung cancer cells in a dose-dependent manner. Quercetin was able to significantly inhibit the proliferation of the As-treated cells over a period of 5 weeks. In addition, quercetin induced ROS-mediated DNA double-strand breaks in the As-treated lung cancer cells. We also showed that ROS generation induced by quercetin activated caspase-3 to a sufficient level to induce DNA damage but insufficient to induce death in As-treated lung cancer cells. Moreover, transient activation of caspase-2 was detected in quercetin- and As-cotreated cells. The flow cytometry-based cell cycle analysis showed that the antiproliferative function of quercetin was mediated by S-phase cell cycle arrest, which was associated with upregulation of the Ataxia Telangiectasia-mutated (ATM), but not ATM and RAD3-related. In conclusion, quercetin synergized the As-driven ROS generation and DNA damage, and induced the S-phase arrest, thus inhibiting the proliferation of As-exposed lung cancer cells. This data suggested that quercetin is an alternative reagent to chemo-drugs to prevent the growth of As-exposed lung cancer cells.

Arsenic poisoning is a geochemical disease that seriously endangers human health. The liver is one of the important target organs for arsenic poisoning, several studies have shown that oxidative stress plays an important role in arsenic-induced liver damage. However, the specific mechanism of arsenic-induced oxidative stress has not yet been fully elucidated, and currently, there are no effective intervention measures for the prevention and treatment of arsenic-induced liver damage. In this study, the effect of the Nrf2/GPX4 signaling pathway and oxidative stress in the arsenic-induced liver damage was first evaluated. The results show that arsenic can activate the Nrf2/GPX4 signaling pathway and increase the oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. Moreover, when we applied the Nrf2 inhibitor, the promoting effect of arsenic on liver damage was alleviated by inhibiting the activation of the Nrf2/GPX4 signaling pathway. Subsequently, the Rosa roxburghii Tratt [Rosaceae] (RRT) intervention experiments in cells and arsenic poisoning population were designed. The results revealed that RRT can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. This study provides some limited evidence that arsenite can activate Nrf2/GPX4 signaling pathway to induce oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. The second major finding was that Kaji-ichigoside F1 may be a potential bioactive compound of RRT, which can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. Our study will contribute to a deeper understanding of the mechanisms in arsenic-induced liver damage, these findings will identify a possible natural medicinal food dual-purpose fruit, RRT, as a more effective prevention and control strategies for arsenic poisoning.

Environmental exposure to arsenic (As) and fluoride (F) in the recent year has been increased because of excessive use of naturally contaminated ground water. Surface water is also regularly contaminated with these elements in various industrial areas. Arsenicosis and fluorosis upon individual exposure of As and F are reported in many studies. A syndrome of endemic As poisoning and fluorosis occurs during concurrent exposure of As and F. Previous reports showed synergistic, antagonistic and independent effects of these two compounds, although few recent reports also revealed antagonistic effects after co-exposure. Interaction during intestinal absorption and influence of F on As metabolism might be the cause of antagonism. The synergism/antagonism is thought to depend on the dose and duration of the co-exposure. However, the detailed mechanism is still not fully understood and needs further studies. Removal technologies of As and F from contaminated water is available but removal of such contaminants from food is yet to be developed. Antioxidants are useful to mitigate the toxic effects of As and F. This review focused on the effect of co-exposure, amelioration as well as removal techniques of As and F.

The World Health Organization (WHO) estimates that around ~ 150 million people in 70 different countries have been consuming water with arsenic levels higher than the recommended limit of 10 µg/L. Here we describe the concentrations of inorganic arsenic in drinking water in homes of pregnant women living in the province of Tacna, near the southern border of Peru. 161 pregnant women were enrolled in their second trimester of pregnancy. A total of 100 mL drinking water was collected in each household from the source of most common use. Inorganic arsenic was categorized into three levels with a commercial kit. Thirty percent of women had drinking water ≤ 10 µg/L (the WHO recommended level), 35% had 25 µg/L, and 35% had greater than 50 µg/L. Low arsenic levels were found in the southernmost homes, supplied by groundwater, while high levels were found in the northern and metropolitan homes supplied by river water.

Neurotoxicity is a serious health problem of patients chronically exposed to arsenic. There is no specific treatment of this problem. Oxidative stress has been implicated in the pathological process of neurotoxicity. Polyphenolics have proven antioxidant activity, thereby offering protection against oxidative stress. In this study, we have isolated the polyphenolics from

Arsenic, as a human carcinogen, has posed a certain threat to environmental health globally. However, the underlying mechanism of the arsenic carcinogenic effect remains largely undetermined. The up-regulation of MDM2 seems to play a crucial part in tumors in especial carcinomas of the diffuse type. The interaction of MDM2 and p53 is closely relevant to the pathogenesis of tumors. In this study, we aimed to investigate the effect on MDM2, p53, and their phosphorylation after As(III). In the epidemiological study, we investigated that MDM2 expression was up-regulation and was positively linked to methylated metabolites (monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) after As(III)-exposure. In vitro studies employing A549 and 16HBE cells confirmed the epidemiological data. Studies on MDM2 phosphorylation sites consisting of Ser166, Ser260, and Ser394 in response to arsenic exposure, which have not been studied presently, indicated that As(III) could induce the expression of MDM2 phosphorylation. Moreover, we studied the alterations of p53 and its N-terminus phosphorylation sites of Ser9, Ser15, and Ser33, which demonstrated that p53 and its phosphorylation were highly expressed after As(III) exposure. Subsequently, Co-immunoprecipitation assays validated our hypothesis that the bonding of MDM2 and p53 was altered by arsenic exposure. What's more, outcomes coming from different cell types of A549, 16HBE, and 60 T-16HBE revealed that MDM2 and its phosphorylation expression existed a significant difference. The study provides evidence that As(III) and its methylated metabolites modulate the expression of MDM2, p53, and their phosphorylation and then affect the interaction between MDM2 and p53.

This paper presents a new method for the simultaneous speciation analysis of arsenic (As(III)-arsenite, As(V)-arsenate, DMA-dimethylarsinic acid, MMA-methylarsonic acid, and AsB-arsenobetaine) and selenium (Se(IV)-selenite, Se(VI)-selenate, Se-Methionine, and Se-Cystine), which was applied to a variety of seafood and onion samples. The determination of the forms of arsenic and selenium was undertaken using the High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry (HPLC–ICP–MS) analytical technique. The separation of both organic and inorganic forms of arsenic and selenium was performed using two analytical columns: an anion exchange column, Dionex IonPac AS22, containing an alkanol quaternary ammonium ion, and a double bed cation–anion exchange guard column, Dionex Ion Pac CG5A, containing, as a first layer, fully sulfonated latex for cation exchange and a fully aminated layer for anion exchange as the second layer. The ammonium nitrate, at pH = 9.0, was used as a mobile phase. The method presented here allowed us to separate the As and Se species within 10 min with a suitable resolution. The applicability was presented with different sample matrix types: seafood and onion.

Edible seaweeds with a relatively high total arsenic concentration have been a global concern. As the largest seaweed producer, China contributes about 60 % of the global seaweed production. The present study investigated 20 seaweed species collected from representative seaweed farming sites in the six provinces along the Chinese coastline, of which Saccharina japonica, Undaria pinnatifida, Neopyropia spp., Gracilaria spp., Sargassum fusiforme were listed as the most consumed seaweeds in Food and Agriculture Organization of the United Nations (FAO). The inorganic arsenic (iAs) concentration in most of the seaweeds was below maximum limits (0.3 mg iAs/kg) as seaweed additives for infant food in the National Food Safety Standard of Pollutants in China (GB2762-2017, 2017), except for the species Sargassum, in which the iAs concentration significantly exceeded the limit and ranged from 15.1 to 83.7 mg/kg. Arsenic speciation in 4 cultivated seaweeds grown in both temperate and subtropical zones is reported for the first time. No significant differences in total As and iAs concentration were identified, except slightly higher total As concentration were found in Saccharina japonica growing in the temperate zone. The estimated daily intake (EDI) of toxic iAs via seaweed consumption was generally below the EFSA CONTAM Panel benchmark dose lower confidence limit (0.3 μg/kg bw/day) except for all Sargassum species where the EDI was significantly higher than 0.3 μg/kg bw/day. Moreover, the first-ever reported data on As speciation indicated very high iAs concentrations in Sargassum hemiphyllum and Sargassum henslowianum. To minimize the food chain iAs exposure, reducing both human intake of Sargassum spp. and the used of Sargassum spp. for animal feed is highly recommended. CAPSULE: This study showed that edible seaweed Sargassum spp. consumption may pose a health risk related to inorganic arsenic (iAs) exposure. The risk of iAs exposure via seaweed consumption or livestock is a concern that needs to be monitored. The arsenic accumulation and speciation may be predominantly species-dependent rather than environmental-dependent.