Assessing the potential value and mechanism of Ginkgo biloba L. On coal-fired arsenic-induced skin damage: In vitro and human evidence.

Exposure through arsenic-contaminated air and food caused by the burning of coal is a major environmental public health concern in Guizhou Province of China. Previous studies have shown that immunological dysfunction is involved in the pathogenesis and carcinogenesis of arsenic; however, knowledge regarding effective prevention measures have not been fully examined. The effect of Ginkgo biloba extract (EGb761) on arsenic-induced skin damage of human immortalized keratinocyte cells (HaCaT) was first evaluated in this study. The results showed that 200 µg/mL EGb761 can reduce the expression of miR-155-5p, and the indicators reflecting arsenic-induced skin damage (Krt1, Krt6c and Krt10) in arsenic-exposed cells (P < 0.05), the expression levels of NF-AT1; the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) in cells; and the levels of secreted IL-2 and IFN-γ in cell supernatants were significantly increased (P < 0.05). Further randomized controlled double-blind experiments showed that compared to the placebo control group, the expression level of miR-155-5p in the plasma of the Ginkgo biloba intervention group, the indicators in the serum reflecting arsenic-induced skin damage (Krt1, Krt6c, and Krt10) and the epithelial-mesenchymal transformation (EMT) vimentin were significantly reduced (P < 0.05), but the levels of NF-AT1 and the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) and EMT (E-cadherin) in serum were significantly increased (P < 0.05). Our study provides some limited evidence that Ginkgo biloba L. can increase the expression of NF-AT1 by downregulating the level of miR-155-5p, alleviating immunological dysfunction, and decreasing the expression of EMT biomarkers, thus indirectly improving arsenic-induced skin damage.

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice.

BACKGROUND: Arsenic poisoning affects millions of people. The inorganic forms of arsenic are more toxic. Treatment for arsenic poisoning relies on chelation of extracellularly circulating arsenic molecules by 2,3-dimecaptosuccinic acid (DMSA). As a pharmacological intervention, DMSA is unable to chelate arsenic molecules from intracellular spaces. The consequence is continued toxicity and cell damage in the presence of DMSA. A two-pronged approach that removes extracellular arsenic, while protecting from the intracellular arsenic would provide a better pharmacotherapeutic outcome. In this study, Coenzyme Q10 (CoQ10), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO2) - a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ10 alone or when co-administered with DMSA would nullify arsenite-induced toxicity in mice. METHODS: Group one represented the control; the second group was treated with NaAsO2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO2 and treated with 200 mg/kg CoQ10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination. RESULTS: Administration of CoQ10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ10 and DMSA alone or in combination. Exposure to arsenite resulted in significant elevation of liver and kidney damage markers. The histological analysis of respective organs confirmed arsenic-induced organ damage, which was ameliorated by CoQ10 alone or when co-administered with DMSA. When administered alone, DMSA did not prevent arsenic-driven tissue damage. CONCLUSIONS: Findings from this study demonstrate that CoQ10 and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.

[Biomononitoring of environmental exposure to inorganic arsenic]. / Surveillance biologique de l'exposition environnementale à l'arsenic inorganique.

BACKGROUND AND OBJECTIVES: The French national authority for health (Haute autorité de santé: HAS) and the French clinical toxicology society (Société 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.

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.

Serum Proteomic Profiling Analysis of Rats Chronically Exposed to Arsenic.

BACKGROUND Arsenic (As) is an environmental contaminant, and As pollution in water and soil is a public health issue worldwide. As exposure is associated with the incidence of many disorders, such as arteriosclerosis, diabetes, neurodegenerative diseases, and renal dysfunction. However, the mechanism of As toxicity remains unclear. MATERIAL AND METHODS We investigated the changes in serum protein profiles of rats chronically exposed to As. Twenty healthy rats were randomly divided into 4 groups, and sodium arsenite of varying final concentrations (0, 2, 10, and 50 mg/L, respectively) was add into the drinking water for each group. The administration lasted for 3 months. Two proteomic strategies, isobaric tags for relative and absolute quantitation (iTRAQ), and 2-dimensional gel electrophoresis (2-DE), were employed to screen the differential serum proteins between control and arsenite exposure groups. RESULTS We identified a total of 27 differentially-expressed proteins, among which 9 proteins were significantly upregulated and 18 were downregulated by As exposure. Many of the differentially-expressed proteins were related to fat digestion and absorption, including 5 apolipoproteins, which indicated lipid metabolism may be the most affected by As exposure. CONCLUSIONS This study revealed the influence of As on lipid metabolism, suggesting an increased potential risk of relevant diseases in subjects chronically exposed to As.

The association of tryptophan and phenylalanine are associated with arsenic-induced skin lesions in a Chinese population chronically exposed to arsenic via drinking water: a case-control study.

OBJECTIVES: We investigated the association of specific serum amino acids (AAs) with the odds of arsenic-induced skin lesions (AISL) and their ability to distinguish patients with AISL from people chronically exposed to arsenic. DESIGN: Case-control study. SETTING: Three arsenic-exposed villages in Wuyuan County, Hetao Plain, Inner Mongolia, China were evaluated. PARTICIPANTS: Among the 450 residents aged 18-79 years, who were chronically exposed to arsenic via drinking water, 56 were diagnosed as having AISL (defined as cases). Another 56 participants without AISL, matched by gender and age (±1 year) from the same population, were examined as controls. MAIN OUTCOME MEASURES AND METHODS: AA levels were determined by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics analysis. Potential confounding variables were identified via a standardised questionnaire and clinical examination. Multivariable conditional logistic regression model and receiver operating characteristic curve analyses were performed to investigate the relationship between specific AAs and AISL. RESULTS: Tryptophan and phenylalanine levels were negatively associated with AISL (p<0.05). Compared with that in the first quartile, the adjusted OR of AISL in the second, third and fourth quartiles were decreased by 44%, 88% and 79% for tryptophan and 30%, 80% and 80% for phenylalanine, respectively. The combination of these two higher-level AAs showed the lowest OR for AISL (OR=0.08; 95% CI 0.02 to 0.25; p<0.001). Furthermore, both AAs showed a moderate ability to distinguish patients with AISL from the control, with the area under the curve (AUC; 95% CI) as 0.67 (0.57 to 0.77) for tryptophan and 0.70 (0.60 to 0.80) for phenylalanine (p<0.05). The combined pattern with AUC (95% CI) was 0.72 (0.62 to 0.81), showing a sensitivity of 76.79% and specificity of 58.93% (p<0.001). CONCLUSIONS: Specific AAs may be linked to AISL and play important roles in early AISL identification. TRIAL REGISTRATION NUMBER: NCT02235948.

Associations of Arsenic Exposure With Telomere Length and Naïve T Cells in Childhood-A Birth Cohort Study.

There is limited knowledge of association between arsenic exposure and telomere length (TL) and signal joint T-cell receptor excision circle (sjTREC) that are potential biomarkers of immune senescence and disease susceptibility. We aimed to clarify whether long-term inorganic arsenic exposure influences TL and sjTRECs in childhood. Children born in a longitudinal mother-child cohort were followed-up at 4.5 (n = 275) and 9 years (n = 351) of age. Arsenic exposure was assessed by metabolite concentrations in urine (U-As) from mothers at gestational week 8 (prenatal) and their children at 4.5 and 9 years. TL and sjTRECs were determined in blood cells using quantitative PCR. The oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in plasma was measured by ELISA. In multivariable-adjusted spline regression analyses, both prenatal and childhood arsenic exposure above U-As of 45 µg/l were significantly inversely associated with TL and sjTRECs at 9 years. Fraction of monomethylarsonic acid (MMA) above spline knot 7% were significantly inversely associated with both TL and sjTRECs reflecting increased toxicity due to less-efficient arsenic metabolism in 9--year-old children. Prenatal and childhood arsenic exposure were positively associated with 8-OHdG at 9 years which in turn was inversely associated with sjTRECs at 9 years. However, adjustment with 8-OHdG did not change the estimates of the association of U-As with sjTRECs reflecting little contribution from 8-OHdG-induced oxidative stress. Our findings suggest that chronic arsenic exposure from early life can result in TL attrition and lower production of naïve T cells potentially leading to immunosenescence and immunodeficiency.

Metabolism and disposition of arsenic species after repeated oral dosing with sodium arsenite in drinking water. II. Measurements in pregnant and fetal CD-1 mice.

Arsenic is ubiquitous in the earth's crust, and human diseases are linked with exposures that are similar to dietary intake estimates. Metabolic methylation of inorganic arsenic facilitates excretion of pentavalent metabolites and decreases acute toxicity; however, tissue binding of trivalent arsenic intermediates is evidence for concomitant metabolic activation. Pregnant and fetal CD-1 mice comprise a key animal model for arsenic carcinogenesis since adult-only exposures have minimal effects. This study evaluated inorganic arsenic and its metabolites in pentavalent and trivalent states in blood and tissues from maternal and fetal CD-1 mice after repeated administration of arsenite through drinking water. After 8 days of exposure, DMA species were ubiquitous in dams and fetuses. Despite the presence of MMAIII in dams, none was observed in any fetal sample. This difference may be important in assessing fetal susceptibility to arsenic toxicity because MMA production has been linked with human disease. Binding of DMAIII in fetal tissues provided evidence for metabolic activation, although the role for such binding in arsenic toxicity is unclear. This study provides links between administered dose, metabolism, and internal exposures from a key animal model of arsenic toxicity to better understand risks from human exposure to environmental arsenic.

Amelioration of arsenic-induced toxic effects in mice by dietary supplementation of Syzygium cumini leaf extract.

Arsenic created a serious public health problem in Bangladesh due to its presence in groundwater and dissemination of the toxic effects to millions of people. The scarcity of the treatment options to manage this affected population has made the situation much worse. To find a promising treatment option, this study was undertaken to examine the ameliorating roles of Syzygium cumini leaf extract (SLE) against arsenic-induced toxic effects in mice. Swiss albino mice were divided into four groups where 'control' group received pure water + normal feed, 'arsenic (As)' group received sodium arsenite (NaAsO2)-containing water (10 µg/g body weight/day) + normal feed, 'As+SLE' group received NaAsO2-containing water + feed supplemented with SLE (50 µg/g body weight/day) and finally the 'SLE' group received pure water + feed supplemented with SLE. A gradual increase in body weight gain was observed in control mice; however, the body weight gain in As-exposed mice was decreased. This decrease in body weight gain was prevented in As+SLE group mice that received SLE supplemented feed. Arsenic showed a secondary effect by causing enlargement of spleen, kidney and liver of 'As' group mice and this enlargement of the organs was minimized with SLE supplementation. In addition, SLE abrogated arsenic-mediated elevation of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid and glucose. These results, therefore, suggest that SLE might have future therapeutic value for preventing or reducing arsenic-induced toxic effects.

Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice.

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood.

BACKGROUND: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. OBJECTIVES: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. METHODS: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N=80 women) and DNA methylation (N=93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. RESULTS: U-As concentrations, ranging 10-1251µg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. CONCLUSIONS: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap.

Height and blood chemistry in adults with a history of developmental arsenic poisoning from contaminated milk powder.

BACKGROUND: Arsenic poisoning interferes with bone metabolism in laboratory animal studies, and human studies suggest lowered bone mass density at elevated exposures. As the long-term consequences of developmental arsenic toxicity are poorly known, we carried out a clinical pilot study of survivors of the mass arsenic poisoning of bottle-fed infants in Japan in 1955. OBJECTIVES: The purpose was to evaluate the association between developmental arsenic exposure and physical stature and routine blood chemistry reflecting major organ functions more than 50 years later. METHODS: The study sample consisted of 50 individuals recruited at two hospitals in Okayama Prefecture, Japan: 27 known poisoning victims (14 men and 13 women), and 23 non-exposed local controls of similar age (10 men, 13 women). We collected information from physical examinations that included routine blood counts and blood biochemistry. RESULTS: The average height of the exposed group was 6.5cm below that of the unexposed group (p=0.02), while the latter was in accordance with national data for both sexes. In addition, the exposed participants had a higher mean (SD) serum concentration of alkaline phosphatase (ALP) of 233 (63) U/L than the unexposed participants (191 (44) U/L) (p=0.01). No other statistically significant difference was observed, and liver enzymes were within normal ranges. CONCLUSIONS: Adults who had suffered arsenic poisoning during infancy showed decreased height and elevated ALP that suggests abnormalities in bone metabolism possibly induced by arsenic incorporated in the bone matrix.

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure.

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL/6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation.

Ameliorative effect of two Ayurvedic herbs on experimentally induced arsenic toxicity in calves.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic arsenic poisoning due to contaminated subsoil water is a threat to society in West Bengal, India and in Bangladesh. The human being may also be affected by the exposed cattle from the affected area by consuming milk, egg, meat and others. In Ayurveda, several herbs like Haridra (turmeric), Shunthi (dried ginger root) and others are used for the management of arsenic poisoning. AIM OF THE STUDY: The study was conducted to find out the ameliorative effect of turmeric and ginger powder against experimentally induced arsenic toxicity in calves. MATERIALS AND METHODS: Twenty four calves were divided into four groups (group I, II, III and IV) having six animals in each group. Animals of group I, II and III were orally administered with sodium arsenite at 1mg/kg body weight for 90 days and in addition group II and group III animals were treated orally with turmeric and ginger powder respectively at 10mg/kg body weight from 46th day onwards. Group IV animals were given food and water without drug and served as control. Arsenic content was estimated in faeces, hair, urine and plasma in every 15 days. Bio-chemical, haematological and anti-oxidant parameters were also assessed. RESULTS: Turmeric and ginger powder significantly (P<0.05) reduced the plasma and hair arsenic levels through increased excretion via faeces and urine. Haemoglobin level, TEC and TLC were decreased in groups I, II and III, however these were improved significantly (P<0.05) from 75th day onwards in turmeric and ginger treated groups. Increased activity of AST and ALT were significantly decreased (P<0.05) from 75th day onwards in group II and III. Blood urea nitrogen and plasma creatinine were also significantly decreased (P<0.05) in group II and III than group I from 60th day onwards. The SOD and catalase activity were significantly (P<0.05) reduced in groups I, II and III, but these were restored at the end of the experiment in turmeric and ginger treated groups. CONCLUSION: 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, it may be concluded from the present study that turmeric and ginger can be helpful in the therapy of chronic arsenic toxicity in calves.

Metabolism and toxicity of arsenicals in mammals.

Arsenic (As) is a metalloid usually found in organic and inorganic forms with different oxidation states, while inorganic form (arsenite As-III and arsenate As-v) is considered to be more hazardous as compared to organic form (methylarsonate and dimethylarsinate), with mild or no toxicity in mammals. Due to an increasing trend to using arsenicals as growth promoters or for treatment purposes, the understanding of metabolism and toxicity of As gets vital importance. Its toxicity is mainly depends on oxi-reduction states (As-III or As-v) and the level of methylation during the metabolism process. Currently, the exact metabolic pathways of As have yet to be confirmed in humans and food producing animals. Oxidative methylation and glutathione conjugation is believed to be major pathways of As metabolism. Oxidative methylation is based on conversion of Arsenite in to mono-methylarsonic acid and di-methylarsenic acid in mammals. It has been confirmed that As is only methylated in the presence of glutathione or thiol compounds, suggesting that As is being methylated in trivalent states. Subsequently, non-conjugated trivalent arsenicals are highly reactive with thiol which converts the trivalent arsenicals in to less toxic pentavalent forms. The glutathione conjugate stability of As is the most important factor for determining the toxicity. It can lead to DNA damage by alerting enzyme profile and production of reactive oxygen and nitrogen species which causes the oxidative stress. Moreover, As causes immune-dysfunction by hindering cellular and humeral immune response. The present review discussed different metabolic pathways and toxic outcomes of arsenicals in mammals which will be helpful in health risk assessment and its impact on biological world.

Knockout of arsenic (+3 oxidation state) methyltransferase results in sex-dependent changes in phosphatidylcholine metabolism in mice.

Arsenic (+3 oxidation state) methyltransferase is the key enzyme in the methylation pathway for inorganic arsenic. We have recently shown that As3mt knockout (KO) has a profound effect on metabolomic profiles in mice. Phosphatidylcholine species (PCs) were the largest group of metabolites altered in both plasma and urine. The present study used targeted analysis to investigate the KO-associated changes in PC profiles in the liver, the site of PC synthesis. Results show that As3mt KO has a systemic effect on PC metabolism and that this effect is sex dependent.

Arsenic Metabolism in Children Differs From That in Adults.

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12.Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children's arsenic methylation; an increase in Ery-Se from the 5-95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P = .001), +1.4 pp for %MMA (P = .003), and -3.2 pp for %DMA (P < .001). Despite this, Ery-Se was positively associated with U-As (5-95th percentile: +41 µg/l, P = .026). As expected, plasma folate was inversely associated with %iAs (5-95th percentile: -1.9 pp, P = .001) and positively associated with %DMA (5-95th percentile: +2.2 pp, P = .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research.

Acute arsenic poisoning diagnosed late.

Acute arsenicosis, although having a 'historical' background, is not common in our times. This report describes a case of acute arsenic poisoning, missed initially due to its gastroenteritis-like presentation, but suspected and confirmed much later, when the patient sought medical help for delayed complications after about 2 months.

Assessment of arsenic levels in body samples and chronic exposure in people using water with a high concentration of arsenic: a field study in Kutahya.

OBJECTIVE: This study aimed to evaluate the prevalence of skin lesions, which is a health effect of chronic arsenic (As) exposure, and determine the hair/blood arsenic concentrations of people living in Kutahya villages who are using and drinking tap water with a high concentration of arsenic. MATERIALS AND METHODS: A total of 303 people were included in the present cross-sectional study. A prepared questionnaire form was used to collect the participants' information and environmental history. Skin examination was performed on all participants. Hair, blood and water samples were analyzed using atomic absorption spectroscopy. The cumulative arsenic index (CAI) was calculated for all participants. RESULTS: Villages were divided into two groups according to the arsenic level (<20 µg/L, Group I; >20 µg/L, Group II) in their water. The prevalence of skin lesions, hair and blood arsenic level, and CAI were found to be higher in the Group II participants. There was a positive association between body arsenic levels and CAI in the participants of each group. CONCLUSIONS: The number of skin lesions and arsenic concentrations in body samples were found to increase with the water arsenic level and exposure time. We hope that sharing this study's results with local administrators will help accelerate the rehabilitation of water sources in Kutahya.