Genomic DNA hydroxymethylation reveals potential role in identification of lung injury in coal-burning arsenicosis populations.

Arsenic (As) is a toxic metalloid element that causes lung cancer and multiple non-malignant respiratory diseases. The toxicity of arsenic is mediated in part by epigenetic mechanisms, such as alterations in DNA methylation. While increasing studies have highlighted the potential importance of arsenic exposure to DNA methylation patterns and the subsequent risks for arsenic toxicity, there has been little focus on DNA hydroxymethylation-a negative regulation mechanism of DNA methylation. Therefore, this study aimed to investigate the relationship between genomic DNA methylation/hydroxymethylation and lung injury in arsenicosis populations. First, an increased risk of lung injury and exacerbation of lung function impairment in the arsenicosis population was confirmed. Levels of 5-methylcytosine/deoxycytidine (5 mC/dC), 5-hydroxymethylcytosine/deoxycytidine (5 hmC/dC) and 5 hmC/5 mC in genomic DNA of peripheral blood were decreased in the arsenicosis population compared to in the control. Additionally, multivariate logistic regression models showed an increased risk of chest digital radiography (DR) abnormalities when 5 hmC/dC and 5 hmC/5 mC levels were lower (OR = 3.12 and 3.96, all P < 0.001). For 3 years follow-up, regression analysis showed that a decline in 5 hmC/dC was significantly associated with the decline of lung function parameters [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and maximal mid-expiratory flow (MMEF); ß = 0.167, 0.122 and 0.073, respectively; all P < 0.05]. Using the receiver operating characteristic (ROC) curve, a combination of 5 hmC/5 dC and 5 hmC/5 mC obtained the highest value for distinguishing lung injury in all subjects (AUC = 0.82, P < 0.01). In contrast, in arsenicosis subjects, 5 hmC/dC was better at distinguishing lung injury (AUC = 0.84, P < 0.01). Together, the results revealed that a decrease in genomic DNA hydroxymethylation markers was associated with lung injury in coal-burning arsenicosis populations. Genomic DNA hydroxymethylation could be a novel biomarker for identifying the risk of lung injury caused by coal-burning arsenicosis.

Association and risk of circulating inflammatory markers with hyperglycemia in coal-burning arsenicosis.

BACKGROUND: Several lines of evidence support a significant relationship between exposure to arsenic and diabetes. However, the underlying pathophysiological mechanisms remain incompletely elucidated. OBJECTIVE: This study examined the association and risk of circulating inflammatory mediators with hyperglycemia in coal-induced arsenicosis. METHODS: 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 ß-cell function (HOMA-ß), as well as circulating inflammatory biomarkers i.e., Interleukins-1ß (IL-1ß), IL- 2, IL - 6, IL-10, IL- 17, IL-18 and TNF-α), were determined and analyzed after completing questionnaire investigation and physical examination. RESULTS: 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-ß (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-1ß, 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-1ß and IL-18 on the relationship between arsenic exposure and hyperglycemia was closely associated with pancreatic ß-cell dysfunction, while those of IL-6 and IL-10 on the association between arsenic exposure and hyperglycemia were partially through insulin resistance. CONCLUSIONS: 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.

Arsenic and fluorine in groundwater in northern Mexico: spatial distribution and enrichment factors.

North-central Mexico has groundwater contaminated with arsenic (As) and fluoride (F). Based on the dispersion patterns of these solutes, their sources are linked to felsic volcanic rock fragments and secondary minerals (clays, iron oxyhydroxides) within the alluvium fill of the aquifers. However, little is known about the effect of the enrichment factors for F and As in this area. Natural enrichment factors include evaporation, Ca/Na, and competitive adsorption and desorption from solid phases. This study used 1237 groundwater quality data measurements from 305 sampling sites collected between 2012 and 2019 in the state of Durango in north-central Mexico. To determine the contribution of enrichment factors to As and F content, the study area was divided into four sections, two being in the mountainous part of the state and two in the high plateaus. The data were compared among sections and analyzed using Spearman correlation and Piper and Block diagrams. The results indicate that the main solute enrichment mechanisms are evaporation and weathering of silicates and evaporites. Among the four sections, As, pH, and HCO3 seemed not to vary, F varied slightly, and nitrate and total dissolved solids varied the most. The lack of variation in As among sections is associated to its strong adsorption to clay minerals and iron oxyhydroxides, whereas the diminished F content in the eastern sections is likely linked to the adsorption of F to precipitating calcite (since groundwater is saturated with respect to calcite (SIcalcite = 0.43) and undersaturated for fluorite (SIfluorite = - 1.16). These processes shed light on the distribution of F and As in this area, and are likely operating in other states in northern Mexico and in semi-arid areas elsewhere.

miR-21-regulated M2 polarization of macrophage is involved in arsenicosis-induced hepatic fibrosis through the activation of hepatic stellate cells.

Arsenicosis induced by chronic exposure to arsenic is recognized as one of the main damaging effects on public health. Exposure to arsenic can cause hepatic fibrosis, but the molecular mechanisms by which this occurs are complex and elusive. It is not known if miRNAs are involved in arsenic-induced liver fibrosis. We found that in the livers of mice exposed to arsenite, there were elevated levels of microRNA-21 (miR-21), phosphorylated mammalian target of rapamycin (p-mTOR), and arginase 1 (Arg1); low levels of phosphatase and tensin homolog (PTEN); and more extensive liver fibrosis. For cultured cells, arsenite-induced miR-21, p-mTOR, and Arg1; decreased PTEN; and promoted M2 polarization of macrophages derived from THP-1 monocytes (THP-M), which caused secretion of fibrogenic cytokines, including transforming growth factor-ß1. Coculture of arsenite-treated, THP-M with LX-2 cells induced α-SMA and collagen I in the LX-2 cells and resulted in the activation of these cells. Downregulation of miR-21 in THP-M inhibited arsenite-induced M2 polarization and activation of LX-2 cells, but cotransfection with PTEN siRNA or a miR-21 inhibitor reversed this inhibition. Moreover, knockout of miR-21 in mice attenuated liver fibrosis and M2 polarization compared with WT mice exposed to arsenite. Additionally, LN, PCIII, and HA levels were higher in patients with higher hair arsenic levels, and levels of miR-21 were higher than controls and positively correlated with PCIII, LN, and HA levels. Thus, arsenite induces the M2 polarization of macrophages via miR-21 regulation of PTEN, which is involved in the activation of hepatic stellate cells and hepatic fibrosis. The results establish a previously unknown mechanism for arsenicosis-induced fibrosis.

Arsenic exposure from groundwater: environmental contamination, human health effects, and sustainable solutions.

Arsenic (As) occurs naturally in geologic conditions, but groundwater contamination might also be found due to the consequences of mining, agricultural and industrial processes. Human exposure to As after drinking contaminated water is commonly associated with acute toxicity outcomes and chronic effects ranging from skin lesions to cancer. Integrated actions from environmental and health authorities are needed to reduce exposure, monitoring outcomes, and promotion of actions to offer sustainable As-safe water alternatives. Considering recent research trends, the present review summarizes and discusses current issues associated with the process and effects of contamination and decontamination in an environmental health perspective. Recent findings reinforce the harmful effects of the consumption of As-contaminated water and broaden the scope of related diseases including intestinal maladies, type 2 diabetes, cancers of bladder, kidneys, lung, and liver. Among the main strategies to diminish or remove As from water, the following are highlighted (1) ion exchange system and membrane filtration (micro, ultra, and nanofiltration) as physicochemical treatment systems; (2) use of cyanobacteria and algae in bioremediation programs and (3) application of nanotechnology for water treatment.

Progress in the prevention and control of water-borne arsenicosis in China.

In this report, we provided an overview of the prevalence, control, and prevention of water-borne arsenicosis in China during 2001-2016. Random sampling was continuously performed during 2001-2010 to find villages having high levels of arsenic (>50 µg/L) in drinking water. The high-arsenic-exposure villages with more geographically dispersed water supplies were subsequently analyzed for characteristics of arsenic distribution, and villages with relatively large populations were investigated for arsenicosis. The results showed that among 32,673,677 inhabitants in 36,820 villages, 1,894,587 inhabitants in 2,476 villages were at risk of high arsenic exposure. Among the 33,318 drinking water sources surveyed in 625 high-arsenic-exposure villages, 9,807 drinking water sources that contained high levels of arsenic (>50 µg/L) were identified. The overall prevalence rate of arsenicosis was 1.93%. Further, some representative villages were chosen to monitor arsenicosis annually, showing that the prevalence rate of arsenicosis was lower in villages with arsenic-safe water supplies than in villages without arsenic-safe water supplies. To the best of our knowledge, this report provides the most comprehensive assessment of the distribution of high arsenic exposure and arsenicosis in China until now.

Human arsenic exposure and lung function impairment in coal-burning areas in Guizhou, China.

To evaluate the effect of coal-burning arsenic (As) exposure on lung function and the potential underlying mechanisms, a total of 217 As-exposed subjects and 75 reference subjects were recruited into this study. Hair arsenic (H-As), pulmonary function tests, and serum inflammatory markers CC16, SP-A, MMP-9, and TIMP-1 were evaluated. Residents from As-exposed areas showed higher H-As concentrations (median 0.25 µg/g) than subjects from the reference area (median 0.14 µg/g). Large reductions in lung function parameters were noted in the As-exposed group. A significant negative correlation was observed between H-As concentrations and lung function. Specifically, monotonic negative dose-response relationships were observed between H-As and FEV1(%), FEV1/FVC (%) and FEF75 (%) (all P < 0.05), while the associations between H-As and FVC (%), FEF25 (%), and FEF50 (%) were nonlinear (P for nonlinearity = 0.03, 0.001, 0.01, respectively). In addition, there was a direct positive relationship between H-As and the inflammatory response. Alterations in inflammatory biomarkers (CC16, SP-A, MMP-9, and MMP-9/TIMP-1) were significantly associated with As-induced lung function impairment. Thus, this population-based study revealed that As exposure has significant toxic effects on lung function and increased inflammation may occur during this toxic process. We provide scientific evidence for an As-induced alteration in inflammatory biomarkers and pulmonary damage in an As-exposed population. The results of this study can inform risk assessment and risk control processes in relation to human As exposure in coal-burning arsenicosis areas.

Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment.

Acquired hypopigmented skin changes are commonly encountered by dermatologists. Although hypopigmentation is often asymptomatic and benign, occasional serious and disabling conditions present with cutaneous hypopigmentation. A thorough history and physical examination, centered on disease distribution and morphologic findings, can aid in delineating the causes of acquired hypopigmented disorders. The second article in this 2-part continuing medical education series focuses on conditions with a hypopigmented phenotype. Early diagnosis and appropriate management of these disorders can improve a patient's quality of life, halt disease progression, and prevent irreversible disability.

The effect of association between inefficient arsenic methylation capacity and demographic characteristics on the risk of skin lesions.

This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090µgL-1. The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10µgL-1 with a daily arsenic intake of 3.23±3.75mgday-1 from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48µgg-1Cr), MMA (106.38±135.04 vs. 35.43±39.97µgg-1Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations.

Arsenic in the groundwater: Occurrence, toxicological activities, and remedies.

Arsenic (As) contamination in groundwater has become a geo-environmental as well as a toxicological problem across the globe affecting more than 100-million people in nearly 21 countries with its associated disease "arsenicosis." Arsenic poisoning may lead to fatal skin and internal cancers. In present review, an attempt has been made to generate awareness among the readers about various sources of occurrence of arsenic, its geochemistry and speciation, mobilization, metabolism, genotoxicity, and toxicological exposure on humans. The article also emphasizes the possible remedies for combating the problem. The knowledge of these facts may help to work on some workable remedial measure.

Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients from Malda district, West Bengal- A case study.

Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients was established in Malda district of West Bengal. Out of 182 participants examined, 80 (43.9%) participants showed clinical features of arsenicosis, characterized by arsenical skin lesion (pigmentation and keratosis), while 102 participants did not have any such lesion (control). Experimental results of the twenty eight soils (own field) of the participants showed the mean Olsen extractable and total arsenic concentration of 0.206 and 6.70mgkg-1, respectively. Arsenic concentration in rice grain ranged from 2.00 to 1260µgkg-1 with the mean value of 146µgkg-1. The hazard quotient (HQ) for intake of As by human through consumption of rice varied from 0.03 to 3.52. HQ exceeds 1.0 for drinking water and rice grain grown in the study area in many cases. As high as 77.6% variation in As content in rice grain could be explained by the solubility-free ion activity model. Toxic limit of extractable As in soil for rice in relation to soil properties and human health hazard, associated with consumption of rice grain by human, was established. For example, the permissible limit of Olsen extractable As in soil would be 0.43mgkg-1 for rice cultivation, if soil pH and organic carbon content were 7.5% and 0.50%, respectively. However, the critical limit of Olsen extractable As in soil would be 0.54mgkg-1, if soil pH and organic carbon were 8.5% and 0.75%, respectively. The conceptual framework of fixing the toxic limit of arsenic in soils with respect to soil properties and human health under modeling-framework was established.

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

CONTEXT: Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. OBJECTIVES: To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. METHODS: Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. RESULTS: Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. CONCLUSION: This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

Specific histone modification responds to arsenic-induced oxidative stress.

To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P<0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showed that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: ß=0.16; P=0.042, H3K18ac: ß=-0.24; P=0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO2 treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage.

Current status of arsenic exposure and social implication in the Mekong River basin of Cambodia.

To evaluate the current status of arsenic exposure in the Mekong River basin of Cambodia, field interview along with urine sample collection was conducted in the arsenic-affected area of Kandal Province, Cambodia. Urine samples were analyzed for total arsenic concentrations by inductively coupled plasma mass spectrometry. As a result, arsenicosis patients (n = 127) had As in urine (UAs) ranging from 3.76 to 373 µg L(-1) (mean = 78.7 ± 69.8 µg L(-1); median = 60.2 µg L(-1)). Asymptomatic villagers (n = 108) had UAs ranging from 5.93 to 312 µg L(-1) (mean = 73.0 ± 52.2 µg L(-1); median = 60.5 µg L(-1)). About 24.7 % of all participants had UAs greater than 100 µg L(-1) which indicated a recent arsenic exposure. A survey found that females and adults were more likely to be diagnosed with skin sign of arsenicosis than males and children, respectively. Education level, age, gender, groundwater drinking period, residence time in the village and amount of water drunk per day may influence the incidence of skin signs of arsenicosis. This study suggests that residents in Kandal study area are currently at risk of arsenic although some mitigation has been implemented. More commitment should be made to address this public health concern in rural Cambodia.

Environmental arsenic epidemiology in the Mekong river basin of Cambodia.

We investigated relationship of arsenicosis symptoms with total blood arsenic (BAs) and serum albumin (SAlb) of residents in the Mekong River basin of Cambodia. We found that arsenicosis patients had significantly higher BAs and lower SAlb than asymptomatic villagers (Mann-Whitney U test, p<0.01). Arsenicosis symptoms were found to be 76.4% (1.764 times) more likely to develop among individuals having an SAlb≤44.3gL(-1) than among those who had an SAlb>44.3gL(-1) (OR=1.764, 95% CI=0.999-3.114) and 117.6% (2.176 times) as likely to occur among those with BAs>5.73µgL(-1) than for those having BAs≤5.73µgL(-1) (OR=2.176, 95% CI=1.223-3.872). Furthermore, a significant negative correlation was also found between BAs and SAlb (rs (199)=-0.354, p<0.0001). As such, this study suggests that people with low SAlb and/or high BAs are likely to rapidly develop arsenicosis symptoms.

Joint effects of urinary arsenic methylation capacity with potential modifiers on arsenicosis: a cross-sectional study from an endemic arsenism area in Huhhot Basin, northern China.

A lower arsenic methylation capacity is believed to be associated with various arsenic-related diseases. However, the synergistic effect of the arsenic methylation capacity and potential modifiers on arsenicosis risk is unclear. The current study evaluated the joint effect of the arsenic methylation capacity with several risk factors on the risk of arsenicosis characterized by skin lesions. In total, 302 adults (79 arsenicosis and 223 non-arsenicosis) residing in an endemic arsenism area in Huhhot Basin were included. Urinary levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of arsenic species (iAs%, MMA%, and DMA%), as well as two methylation indices (primary methylation index, PMI, and secondary methylation index, SMI), were calculated to assess the arsenic methylation capacity of individuals. The results showed that a lower methylation capacity, which is indicated by higher MMA% values and lower DMA% and SMI values, was significantly associated with arsenicosis after the adjustment for multiple confounders. The relative excess risk for interactions between higher MMA% values and older age was 2.35 (95% CI: -0.56, 5.27), and the relative excess risk for interactions between higher MMA% values and lower BMI was 1.08 (95% CI: -1.20, 3.36). The data also indicated a suggestive synergistic effect of a lower arsenic methylation capacity (lower DMA% and SMI) with older age, lower BMI, and male gender. The findings of the present study suggest that a lower arsenic methylation capacity was associated with arsenicosis and that certain risk factors may enhance the risk of arsenic-induced skin lesions.

Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure.

Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean ± SD(Standard Deviation)] as 2.41 ± 2.32 vs. 1.22 ± 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 ± 2.33 vs. 0.78 ± 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 ± 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation.

Leukonychia Totalis: An Underreported Sign of Chronic Arsenicosis.

Introduction: Arsenic poisoning results from exposure to arsenic through ingestion, inhalation, or skin contact. Cutaneous and neurological symptoms enable early diagnosis. Diagnostic tests include hair, nail, and urine arsenic levels. Leukonychia can be true, apparent, or pseudoleukonychia, depending on the underlying cause. Case Report: A 27-year-old male on herbal supplement for bodybuilding, presented with whitish discolouration of nails for 2 years and tingling sensation in extremities for 6 months. Electrophysiological tests indicated symmetric sensorimotor polyneuropathy. Arsenic levels were significantly elevated in hair, nails, and herbal supplements. A diagnosis of chronic arsenicosis with leukonychia totalis and early peripheral neuropathy was made. Discussion: Chronic arsenicosis may feature skin changes including pigmentary alterations, palmoplantar keratosis, and the characteristic "raindrops on a dusty road" appearance. Hair loss and nail alterations, such as Mees' lines, are also noted. Arsenic-related neuropathy can be mild or subclinical initially and primarily affects sensory nerve fibres. Total leukonychia due to chronic arsenic exposure has not been reported previously.

Treating chronic arsenic toxicity with high selenium lentil diets.

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans.

Identification of biomarkers for risk assessment of arsenicosis based on untargeted metabolomics and machine learning algorithms.

BACKGROUND: Long-term exposure to inorganic arsenic may lead to arsenicosis. There are, however, currently no validated metabolic biomarkers used for the identification of arsenicosis risk. This study aims to identify metabolites associated with arsenicosis and establish prediction models for risk assessment based on untargeted metabolomics and machine learning algorithms. METHODS: In total, 105 coal-borne arsenicosis patients, with 35 subjects in each of the mild, moderate, and severe subgroups according to their symptom severity, and 60 healthy residents were enrolled from Guizhou, China. Ultra-high performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) was utilized to acquire the plasma metabolic profiles of the studied subjects. Statistical analysis was used to identify disease-associated metabolites. Machine learning algorithms and the identified metabolic biomarkers were resorted to assess the arsenicosis risk. RESULTS: A total of 143 metabolic biomarkers, with organic acids being the majority, were identified to be closely associated with arsenicosis, and the most involved pathway was glycine, serine, and threonine metabolism. Comparative analysis of metabolites in arsenicosis patients with different symptom severity revealed 422 altered molecules, where disrupted metabolism of beta-alanine and arginine demonstrated the most significance. For risk assessment, the model established by a single biomarker (L-carnosine) could undoubtedly discriminate arsenicosis patients from the healthy. For classifying arsenicosis patients with different severity, the model established using 52 metabolites and linear discriminate analysis (LDA) algorithm yielded an accuracy of 0.970-0.979 on calibration set (n = 132) and 0.818-0.848 on validation set (n = 33). CONCLUSION: Altered metabolites and disrupted pathways are prevalent in arsenicosis patients; The disrupted metabolism of one carbon and dysfunction of antioxidant defense system may partially be causes of the systematic multi-organ damage and carcinogenesis in arsenicosis patients; Metabolic biomarkers, combined with machine learning algorithms, could be efficient for risk assessment and early identification of arsenicosis.