Effect of chronic intake of arsenic-contaminated water on liver

The hepatotoxic effect of arsenic when used in therapeutic dose has long been recognized. We described the nature and degree of liver involvement and its pathogenesis due to prolonged drinking of arsenic-contaminated water in West Bengal, India. From hospital-based studies on 248 cases of arsenicosis, hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The portal fibrosis was characterized by expansion of portal zones with streaky fibrosis, a few of which contained leash of vessels. However, portal hypertension was found in smaller number of cases. A cross-sectional epidemiological study was carried out on 7683 people residing in arsenic-affected districts of West Bengal. Out of these, 3467 and 4216 people consumed water-containing arsenic below and above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001). The incidence of hepatomegaly was found to have a linear relationship proportionate to increasing exposure of arsenic in drinking water in both sexes (P < 0.001). In an experimental study, BALB/C mice were given water contaminated with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at 3-month intervals. We observed progressive reduction of hepatic glutathione and enzymes of anti-oxidative defense system associated with lipid peroxidation. Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15 months. Our studies show that prolong drinking of arsenic-contaminated water is associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to be caused by arsenic induced oxystress.     

Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenic

Over six million people in nine districts of West Bengal, India are exposed to very high levels of arsenic primarily through their drinking water. More than 300,000 people showed arsenic-induced skin lesions in these districts. This is regarded as the greatest arsenic calamity in the world. Chronic arsenicosis causes varied dermatological signs ranging from pigmentation changes, hyperkeratosis to non-melanocytic cancer of skin, and also malignancies in different internal organs. Higher incidences of opportunistic infections are found in the arsenic-exposed individuals, indicating that their immune systems may be impaired somehow. We have thus investigated the effect of arsenic on T-cell proliferation and cytokine secretion in 20 individuals with arsenic-induced skin lesions and compared the results with 18 arsenic-unexposed individuals. A marked dose-dependent suppression of Concanavalin A (Con A) induced T-cell proliferation was observed in the arsenic-exposed individuals compared with the unexposed (P < 0.001) individuals. This correlated with a significant decrease in the levels of secreted cytokines by the T cells (TNF-alpha, IFN-gamma, IL2, IL10, IL5, and IL4) in the exposed individuals (P < 0.001). Thus it can be inferred that arsenic exposure can cause immunosuppression in humans.     

Effect of environmental exposure of arsenic on cattle and poultry in nadia district, west bengal, India

A study was undertaken to evaluate an alternative source of arsenicosis in human food chain through livestock. Thirty milch cattle and 20 poultry birds along with their eggs were selected randomly from two endemic villages of Nadia district and one nonendemic villages of Hooghly district in West Bengal, India. Milk, feces, urine, and hair samples of cattle and feed materials, such as water and straw, were collected to analyze arsenic status. Arsenic concentration in egg yolk and albumen from poultry eggs and different poultry organs after culling was estimated. Distribution of arsenic in animal body indicates that major portion of arsenic was eliminated through feces, urine, and milk. Poultry egg yolk, albumen, and poultry products retain arsenic in all organs. Cows and poultry birds reared in endemic zone retain significantly higher concentration of arsenic. Consumption of egg, agricultural produces grown in contaminated soil, and milk might have produced arsenicosis and may be considered as alternative source of arsenic contamination.     

Chronic arsenicosis in goats with special reference to its exposure, excretion and deposition in an arsenic contaminated zone

Thirty goats were selected randomly from a village of Nadia district, West Bengal according to the previous reports of human being suffering from chronic arsenicosis. Environmental samples viz. drinking water, rice plants and grass used for goat and biological samples viz. blood, urine, faeces, hair and meat were collected to evaluate the arsenic status. It was found that arsenic concentration in both environmental and biological samples was significantly (p<0.01) higher rather than respective samples on control zone. Bio-concentration factor (BCF) and bio-transfer factor (BTF) are indicated to evaluate the subclinical toxicity in goat as they do not exhibit clinical manifestation like human beings.     

Assessment of DNA damage in peripheral blood lymphocytes of individuals susceptible to arsenic induced toxicity in West Bengal, India

Assessment of DNA damage was carried out using alkaline comet assay in lymphocytes of 30 individuals exposed to high levels of arsenic (247.12+/-18.93 microg/l) through contaminated groundwater in North 24 Parganas district, West Bengal, India. All of them exhibited high arsenic contents in nail (4.20+/-0.67 microg/g), hair (2.06+/-0.20 microg/g) and urine (259.75+/-33.89 microg/l) samples and manifested various arsenical skin lesions. Unexposed samples were collected from 30 residents of the unaffected East Midnapur district with very little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking water. The results were evaluated principally by manual analysis of comets and partly by computerized image analysis. Both the analytical methods exhibited a high degree of agreement in results. The exposed participants expressed significantly higher DNA damage (p < 0.01) in their lymphocytes than the unexposed participants. Alkaline comet assay was also combined with formamidopyrimidine-DNA glycosylase enzyme digestion to confirm that arsenic induced oxidative base damage in the lymphocytes. Significant positive trend effects of comet lengths in relation to arsenic levels in water prove that DNA damage can be used as a sensitive biomarker of arsenic exposure. This study demonstrates that arsenic induced significant DNA damage in the exposed participants, which could correspond to a higher susceptibility to arsenic induced toxicity and carcinogenicity.     

Intake of arsenic from water, food composites and excretion through urine, hair from a studied population in West Bengal, India.

To evaluate the main intake source of arsenic by the villagers from arsenic-affected families in Jalangi and Domkol blocks in Mushidabad district, West Bengal-India, we determined the concentrations of arsenic in tube-well water and in food composites, mainly including vegetables and cereals collected from the surveyed families which were cultivated in that region. The daily dietary intakes of arsenic by the villagers were estimated and the excretions of arsenic through urine and hair were determined. The arsenic concentrations in hair and urine of the studied population living in mild (2.78 microg/L), moderate (30.7 microg/L) and high (118 microg/L) arsenic-affected families were 133, 1,391 and 4,713 microg/kg and 43.1, 244 and 336 microg/L, respectively. The linear regressions show good correlations between arsenic concentrations in water vs hair (r(2)=0.928, p<0.001) and water vs urine (r(2)=0.464, p<0.01). Approximately 29.4%, 58.1% and 62.1% of adult population from mild, moderate and high arsenic-affected families were suffering from arsenical skin manifestations. The mean arsenic concentrations of food composites (vegetables and cereals) in high arsenic-affected families are not significantly different from mild arsenic-affected families. The daily dietary intakes of arsenic from water and food composites of the studied population, living in high, moderate and mild arsenic-affected families were 568, 228 and 137 microg, respectively. The linear regressions show good correlations between arsenic concentrations in hair vs daily dietary intake (r(2)=0.452, p<0.001) and urine vs daily dietary intake (r(2)=0.134, p<0.001). The water for drinking contributed 6.07%, 26.7% and 58.1% of total arsenic in our study from mild, moderate and high arsenic-affected families. The result suggested that the contaminated water from high arsenic-affected families should be the main source for intake of arsenic. On contrary, the contribution of arsenic-contaminated food composites from mild and moderate arsenic-affected families might be the main source for intake of arsenic. The Food and Agriculture Organization/World Health Organization (FAO/WHO) provisional tolerable weekly intake (PTWI) values of arsenic in our study were 3.32, 5.75 and 12.9 microg/kg body weight/day from mild, moderate and high arsenic-affected families, respectively, which is higher than the recommended PTWI value of arsenic (2.1 microg/kg body weight/day).     

Neurosensory effects of chronic human exposure to arsenic associated with body burden and environmental measures

Exposure to arsenic in drinking water is known to produce a variety of health problems, including peripheral neuropathy. Auditory, visual and somatosensory impairment have been reported in Mongolian farmers living in the Yellow River Valley, where drinking water is contaminated by arsenic. In the present study, sensory tests, including pinprick and vibration thresholds, were administered to 320 residents with well-water arsenic levels, ranging from non-detectable to 690 microg/L. Vibration thresholds in the second and fifth fingers of both hands were measured using a vibrothesiometer. Drinking water, urine and toenail samples were obtained to assess arsenic exposure and body burden. Regression analyses indicated significant associations of pinprick scores and vibration thresholds with all arsenic measures. Vibration thresholds were more strongly associated with urinary than water or nail arsenic measures, but odds ratios for decreased pinprick sensitivity were highest for the water arsenic measure. Results of the current study indicate neurosensory effects of arsenic exposure at concentrations well below the 1000 microg/L drinking water level specified by NRC, and suggest that non-carcinogenic end-points, such as vibration thresholds, are useful in the risk assessment of exposure to arsenic in drinking water.     

Arsenic speciation in the urine and hair of individuals exposed to airborne arsenic through coal-burning in Guizhou,PR China

The extent of exposure of residents of Changqing (Guizhou, PR China) to arsenic through coal-burning was investigated. Despite the low coal-arsenic content (56.3+/-42.5 mg As kg(-1)) when compared with coals collected at different location and times from the same province, more than 30% of the study subjects have shown symptoms of arsenicosis. Coal, urine, hair, and water samples were collected in mid-September 2001 and analysed for arsenic. The average urinary and hair-arsenic concentrations in the exposed subjects were 71.4+/-37.1 microg As g(-1) creatinine (control 41.6+/-12.1) and 7.99+/-8.16 mg kg(-1), respectively. A positive correlation between the hair and urinary-arsenic concentration (R(2)=0.601) was found. There was no significant difference between females and males for both urinary and hair-arsenic concentrations. Females were found to have a higher dimethylarsinic acid but lower percentages of inorganic arsenic and monomethylarsonic acid in their urine than males.     

Chronic Arsenicosis of Cattle in West Bengal and It's Possible Mitigation by Sodium Thiosulfate

Thirty milch cows having arsenic concentration in hair varying from 3 to 4 mg/kg from Dakhin Panchpota village of Nadia district, West Bengal, were divided into three equal groups where high amount of arsenic is reported to be present in soil and ground water. Groups II and III received, respectively, sodium thiosulfate 20 and 40 g to each animal for 30 days as a pilot study, whereas group I served as untreated control. Arsenic content of milk, feces, hair, and urine was estimated before and after administration of sodium thiosulfate orally at two dose level once daily for 1 month. Paddy straw, mustard oil cake, and water fed by animals were also assayed. Sodium thiosulfate significantly decreased arsenic load in milk, urine, and hair after 1 month. In milk, arsenic concentration was decreased significantly which may be beneficial for animal and human beings.     

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose-response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions.     

Speciation of arsenic in human nail and hair from arsenic-affected area by HPLC-inductively coupled argon plasma mass spectrometry

Nail and hair are rich in fibrous proteins, i.e., alpha-keratins that contain abundant cysteine residues (up to 22% in nail and 10-14% in hair). Although they are metabolically dead materials in the epidermis, the roots are highly influenced by the health status of the living beings and their analyses are used as a tool to monitor occupational and environmental exposure to toxic elements. The aims of the present study are to speciate arsenicals in human nail and hair and also to judge whether they should be used as a biomarker to arsenic (As) exposure and/or toxicity. All human fingernail and hair samples (n = 47) were collected from the As-affected area of West Bengal, India. Speciation of arsenicals in water extracts of fingernails and hair at 90 degrees C was carried out by HPLC-inductively coupled argon plasma mass spectrometer (ICP MS). Fingernails contained iAs(III) (58.6%), iAs(V) (21.5), MMA(V) (7.7), DMA(III) (9.2), and DMA(V) (3.0), and hair contained iAs(III) (60.9%), iAs(V) (33.2), MMA(V) (2.2), and DMA(V) (3.6). Fingernails contained DMA(III), but hair did not. The higher percentage of iAs(III) both in fingernails and hair than that of iAs(V) suggests more affinity of iAs(III) to keratin. Although all arsenicals in fingernails and hair correlate to As exposure positively, As speciation in fingernails seems to be more correlated with arsenism than that in hair. Exogenous contamination is a confounding factor for hair to consider it as a biomarker, whereas this is mostly absent in fingernails, which recommends it to be a better biomarker to arsenic exposure. DMA(III) content in fingernails and DMA(V) contents in both fingernails and hair could be the biomarker to As exposure.     

Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water

Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.     

Residential exposure to drinking water arsenic in Inner Mongolia, China

In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.     

Impact of sedimentary arsenic through irrigated groundwater on soil, plant, crops and human continuum from Bengal delta: Special reference to raw and cooked rice

Existence of arsenic-rich (exceeds 2,000 mg/kg) iron pyrite in Bengal delta sediments is responsible for arsenic release in aquifer. Ingestion of contaminated drinking water is not the only elevated source of arsenic to the diet. Irrigation of agricultural fields with arsenic-contaminated groundwater has led to arsenic build-up in soil, with subsequent elevation of arsenic in crops grown on these soils. About 50.7 and 11.2 kg of arsenic are withdrawn per year from 23 and 18 shallow tubewells, used for agricultural irrigation in the studied two districts Murshidabad and Nadia, respectively and deposited on lands throughout the year. Considerable higher amounts of arsenic are accumulated in paddy plants. Mean arsenic concentration in food categories is 107 microg/kg. Arsenic concentrations are high in cooked food and skin of the vegetables. Arsenic concentration in cooked rice increases with water arsenic concentration. About 70.2% of arsenic is recovered by using the analytical speciation extraction method. Inorganic arsenic and DMA contribute 89.5% and 10.5% of the total content of arsenic in food, respectively. About 0.081% and 1.57% of arsenic are accumulated in rice grain from arsenic-deposited lands and contaminated soils. The daily dietary intake of inorganic arsenic (mug/kg body wt./day) by an adult from rice grain itself (2.32) is higher than the WHO recommended PTDI value of inorganic arsenic (2.1) and inorganic arsenic contributes 96.8% of the total dietary intakes of arsenic. Population exposed to arsenic toxicity has been identified.     

Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water.

BACKGROUND: Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. METHODS: Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/-14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. RESULTS: Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases. CONCLUSION: 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.     

Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71 mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06 mg-year), medium (1.37-3.55 mg-year), and high (4.26-48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity.     

Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India

A speciation technique for arsenic has been developed using an anion-exchange high-performance liquid chromatography/inductively coupled argon plasma mass spectrometer (HPLC/ICP MS). Under optimized conditions, eight arsenic species [arsenocholine, arsenobetaine, dimethylarsinic acid (DMA(V)), dimethylarsinous acid (DMA(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), arsenite (As(III)), and arsenate (As(V))] can be separated with isocratic elution within 10 min. The detection limit of arsenic compounds was 0.14-0.33 microg/L. To validate the method, Standard Reference Material in freeze-dried urine, SRM-2670, containing both normal and elevated levels of arsenic was analyzed. The method was applied to determine arsenic species in urine samples from three arsenic-affected districts of West Bengal, India. Both DMA(III) and MMA(III) were detected directly (i.e., without any prechemical treatment) for the first time in the urine of some humans exposed to inorganic arsenic through their drinking water. Of 428 subjects, MMA(III) was found in 48% and DMA(III) in 72%. Our results indicate the following. (1) Since MMA(III) and DMA(III) are more toxic than inorganic arsenic, it is essential to re-evaluate the hypothesis that methylation is the detoxification pathway for inorganic arsenic. (2) Since MMA(V) reductase with glutathione (GSH) is responsible for conversion of MMA(V) to MMA(III) in vivo, is DMA(V) reductase with GSH responsible for conversion of DMA(V) to DMA(III) in vivo? (3) Since DMA(III) forms iron-dependent reactive oxygen species (ROS) which causes DNA damage in vivo, DMA(III) may be responsible for arsenic carcinogenesis in human.     

Structure-function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity

Chronic arsenicosis, a major public health concern in India and Bangladesh, is mainly caused by ingestion of arsenic (As) contaminated ground water. Although this problem has been studied extensively, the mechanism of toxicity remains unknown. This paper investigates the process of trivalent arsenicals binding to hemoglobin (Hb) in chronic arsenicosis patients and consequent modification in the structure–function activity of Hb. In this work peroxidase activity, thermal denaturation profile, oxygen releasing capacity and hydrodynamic diameter have been evaluated for the Hb collected from subjects suffering with chronic arsenicosis. Increased peroxidative activity suggests altered oxidative status of Hb in the diseased state. The thermal denaturation profile indicates the Hb molecule to be more susceptible to unfolding in the pathologic state. The enhanced oxygen releasing capacity and significant reduction in hydrodynamic diameter of Hb is also observed in the diseased condition, suggesting conformational alterations in the Hb molecule. Finally, trivalent arsenic is found to bind with freshly isolated Hb from arsenicosis patients, binding affinity constant being 0.256 μM^?1. The binding is positively cooperative with a Hill coefficient of +2.961 and isosbestic points at specific wavelengths. Thus, our work explores the structure–function property of Hb in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association may play a crucial role in exerting the pathway for arsenic toxicity. Copyright © 2011 John Wiley & Sons, Ltd.     

Recovery from severe arsenic-induced peripheral neuropathy with 2,3-dimercapto-1-propanesulphonic acid

Case Report: A 33-year-old female with a 1.5-year history of multisystem illness was diagnosed with arsenic poisoning. Twenty-four-hour urine arsenic was 1030 microg/dL (normal 0-99) and root hair arsenic was 130 microg/g (normal 0-3). Despite treatment with succimer meso-2,3-dimercaptosuccinic acid, her neuropathy progressed to ventilator dependence and quadriplegia. Subsequent intravenous treatment with 2,3-dimercapto-1-propanesulfonic acid sodium salt was associated with arsenic diuresis, marked neuropathic improvement, and extubation. At 1-year follow-up, neuropathy was limited to mild distal lower extremity weakness and sensory loss. The use of 2,3-dimercapto-1-propanesulphonic acid in the treatment of severe arsenic neuropathy was associated with increased urinary elimination of arsenic and dramatic clinical recovery.     

Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, China

The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 microg of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and >100 microg of As/L, respectively. Controlling for age and body weight (n=3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n=3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and >100 microg of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.