Chronic arsenic poisoning: A sinister cause of peripheral neuropathy in a young couple.

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.

Chemopreventive Role of Black Tea Extract in Swiss Albino Mice Exposed to Inorganic Arsenic.

OBJECTIVE: Chronic exposure to inorganic arsenic (iAs) may cause a number of health problems including skin cancer. Present study is aimed to look into the potential of black tea extract (BTE) to prevent the development of skin carcinoma in Swiss albino mice. METHODS: The study was done on Swiss albino mice, chronically exposed to inorganic arsenic. 150 mice were housed in different cages, 5 in each cage. The control mice did not receive any treatment. Mice were sacrificed at 30, 90, 180, 270 and 330 days. Development of carcinogenesis was assessed by histological studies. Generation of Reactive Oxygen Species (ROS) and Reactive Oxygen Species (RNS) were estimated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Greiss reagent respectively, and their consequences on DNA (by Micronuclei and Comet assay), protein (by protein carbonyl assay kit) and lipid (by lipid peroxidation) were estimated. Activity of antioxidant enzymes, along with total antioxidant capacity were measured by respective kits. Repair percentage was obtained by Comet assay. Western blotting was employed to study the expression of repair enzymes and expression of cytokines. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique was employed to study the activity of various cytokines. RESULTS: At 330 days, invasive squamous cell carcinoma of the skin developed. With increasing time generation of ROS and RNS increased, causing damage to DNA, protein and lipid. Antioxidant defence system gets repressed with time. Capacity to repair the DNA damage is inhibited by iAs, due to alteration in repair enzymes - XRCC I, DNA Ligase I, PARP I, ERCC1, ERCC2, XPA, DNA Ligase IV, DNA PKc and Ku-70. Another consequence of iAs exposure is chronic inflammation due to disrupted cytokine level. Intervention with BTE reverses these deleterious effects, preventing development of skin carcinogenesis.

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.

Treatment of lead and arsenic poisoning in anuric patients - a case report and narrative review of the literature.

BACKGROUND: Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered. CASE PRESENTATION: We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance. CONCLUSION: Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.

Rapid onset of multiple concurrent squamous cell carcinomas associated with the use of an arsenic-containing traditional medicine for chronic plaque psoriasis.

We report a case of a 46-year-old Vietnamese man who developed widespread, numerous and concurrent cutaneous squamous cell carcinomas (SCCs) in non-sun exposed skin areas after taking a traditional medicine (TM) formulation for chronic plaque psoriasis. The SCC lesions began to develop within 12-15 months after beginning the arsenic-containing TM. The patient experienced both acute and chronic symptoms consistent with arsenic exposure. Laboratory investigation of a collected hair sample showed a significant arsenic level. The TM formulation used by the patient was tested and demonstrated an extremely high concentration of arsenic.

Histopathological Changes in Arsenic Kushta Induced Nephrotoxicity in Wistar Rats.

OBJECTIVE: To determine the nephrotoxic effects of arsenic kushta (Kushta Sam-ul-Far) in Wistar rats. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Morbid Anatomy and Histopathology, University of Health Sciences, Lahore from May to August 2014. METHODOLOGY: This experimental study was conducted on 48 healthy Wistar rats, each weighing 200 - 250 grams. The rats were randomly divided into 4 experimental groups each containing 12 rats. Group I was taken as control given flour pellets. Group II was given single dose (180 mg/kg) of arsenic kushta for 2 weeks. Group III received 150 mg/kg of arsenic kushta for 12 weeks; whereas, group IV was also given 150 mg/kg of arsenic kushta for 12 weeks along with 75 mg of BSA (bovine serum albumin). Histopathological changes in glomeruli, tubules and interstitium were noted in the kidney. RESULTS: Mesangial proliferation, thickening of basement membrane, necrosis, and interstitial edema were mainly observed in all the above groups except group I which served as control. These changes were seen in greater severity in high dose groups and the group given BSA injection along with kushta (group III, IV). CONCLUSION: Herbo-mineral preparations of arsenic kushta are nephrotoxic in rats and may have similar toxic effects in human beings.

Inhibition of Oxidative Stress and Enhancement of Cellular Activity by Mushroom Lectins in Arsenic Induced Carcinogenesis.

Chronic arsenicosis is a major environmental health hazard throughout the world, including India. Animals and human beings are affected due to drinking of arsenic contaminated ground water, due to natural mineral deposits, arsenical pesticides or improperly disposed arsenical chemicals. Arsenic causes cancer with production of free radicals and reactive oxygen species (ROS) that are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous non-enzymatic antioxidants. Dietary antioxidant supplements are useful to counteract the carcinogenesis effects of arsenic. Oyster mushroom lectins can be regarded as ingredients of popular foods with biopharmaceutical properties. A variety of compounds have been isolated from mushrooms, which include polysaccharides and polysaccharopeptides with immune-enhancing effects. Lectins are beneficial in reducing arsenic toxicity due to anticarcinogenetic roles and may have therapeutic application in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent.

Neurological and neuropsychological functions in adults with a history of developmental arsenic poisoning from contaminated milk powder.

During the summer of 1955, mass arsenic poisoning of bottle-fed infants occurred in the western part of Japan due to contaminated milk powder, and more than 100 died; some childhood victims were later found to suffer from neurological sequelae in adolescence. This unique incident enabled us to explore infancy as a critical period of arsenic exposure in regard to developmental neurotoxicity and its possible persistence through adulthood. The purpose of this work is to evaluate the association between developmental arsenic exposure and the neurological outcomes more than 50 years later. We conducted a retrospective cohort study during the period from April 2012 to February 2013 in two hospitals in Okayama Prefecture, Japan. The study sample consisted of 50 individuals: 27 known poisoning victims from Okayama Prefecture, and 23 non-exposed local controls of similar age. In addition to neurological examination, we adapted a battery of neurophysiological and neuropsychological tests to identify the types of brain functions affected by early-life arsenic exposure. While limited abnormalities were found in the neurophysiological tests, neuropsychological deficits were observed. Except for Finger tapping, all test scores in the exposed group--Vocabulary and Block Design from Wechsler Adults Intelligent Scale III, Design memory subtest from Wide Range Assessment of Memory and Learning 2, and Grooved pegboard test--were substantially below those obtained by the unexposed. The exposed group showed average performance at least 1.2 standard deviations below the average for the controls. Exposed participants performed less well than controls, even after exclusion of subjects with recognized disabilities or those with a high level of education. Adults who had suffered arsenic poisoning during infancy revealed neuropsychological dysfunctions, even among those subjects not recognized as having disabilities. Developmental neurotoxicity due to arsenic likely results in permanent changes in brain functions.

Protective effects of thymoquinone against apoptosis and oxidative stress by arsenic in rat kidney.

We aimed to investigate the protective role of thymoquinone (TQ) by targeting its antiapoptotic and antioxidant properties against kidney damage induced by arsenic in rats. We have used the 24 male Sprague-Dawley rats. Rats were divided into three groups. Physiological serum in 10 mL/kg dose as intragastric was given to the control group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) was given to the arsenic group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) and TQ (10 mg/kg, intragastric by gavage for 15 days) was given to the arsenic + TQ group. After 15 days, the animals' kidneys were taken theirs, then we have performed histological and apoptotic assessment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde (MDA) levels have examined as the oxidative stress parameters. We have determined the levels of arsenic. Increased renal injury and apoptotic cells have been detected in the arsenic group. Degenerative changes in the arsenic + TQ group were diminished. Although the MDA levels were augmented in the arsenic group, SOD, CAT and GSH-Px enzyme activities were lessened than the other groups. Our findings suggest that TQ may impede the oxidative stress, the cells have been damaged and also the generation of apoptotic cells arisen from arsenic. TQ plays a protective role against arsenic-induced toxicity in kidney and may potentially be used as a remedial agent.

Arsenic exposure and impaired lung function. Findings from a large population-based prospective cohort study.

RATIONALE: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. OBJECTIVES: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. METHODS: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator-administered pulmonary function assessed during follow-up. MEASUREMENTS AND MAIN RESULTS: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (-46.5 ml; P < 0.0005) and FVC (-53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (-48.3 ml; P < 0.005) and FVC (-55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (-74.4 ml, P < 0.01; and -116.1 ml, P < 0.05) and FVC (-72.8 ml, P = 0.02; and -146.9 ml, P = 0.004), respectively. CONCLUSIONS: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range.

Baseline comorbidities in a skin cancer prevention trial in Bangladesh.

BACKGROUND: Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest that antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods and baseline analyses from the Bangladesh Vitamin E and Selenium Trial (BEST), a population-based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. MATERIALS AND METHODS: Bangladesh Vitamin E and Selenium Trial is a 2 × 2 full factorial, double-blind, randomized controlled trial of 7000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 µg daily) for the prevention of nonmelanoma skin cancer. RESULTS: In cross-sectional analyses, we observed significant associations of skin lesion severity with male gender (female prevalence odds ratio (POR) = 0.87; 95% CI = 0.79-0.96), older age (aged 36-45 years, POR = 1.27; 95% CI = 1.13-1.42; aged 46-55 years, POR = 1.44; 95% CI = 1.27-1.64 and aged 56-65 years, POR = 1.50; 95% CI = 1.26-1.78 compared with aged 25-35 years), hypertension (POR = 1.29; 95% CI = 1.08-1.55), diabetes (POR = 2.13; 95% CI = 1.32-3.46), asthma (POR = 1.55; 95% CI = 1.03-2.32) and peptic ulcer disease (POR = 1.20; 95% CI = 1.07-1.35). CONCLUSIONS: We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond.

Changes in the synaptic structure of hippocampal neurons and impairment of spatial memory in a rat model caused by chronic arsenite exposure.

Many epidemiological studies and in vitro experiments have found that chronic arsenic exposure may influence memory formation. The goal of this study was to create an animal model of memory impairment induced by chronic arsenite exposure and to study the underlying mechanisms. Sixty male Sprague-Dawley (SD) male rats were randomly divided into a control group, a low-dose sodium arsenite exposure group and a high-dose sodium arsenite exposure group. Sodium arsenite was administered by adding it to drinking water for 3 months. Then, the spatial memory of the rats was examined with Morris water maze and Y maze. The concentration of arsenic in the blood and the brain was determined by an atomic fluorescence absorption spectrometer. The ultra-structure of hippocampal neurons was observed by an electron microscope. Timm staining was used for observing mossy fibers. We found that the concentration of arsenic in the blood and the brain increased in a dose-response manner (P<0.05). The performance of rats in the arsenite exposed group (15 mg/kg) was significantly impaired in the Morris water maze and Y maze tasks than those in the control group (P<0.05). Sodium arsenite exposure resulted in abnormal structural changes in the myelin sheaths of nerve fibers and decreases in the terminals of mossy fibers. Together, chronic sodium arsenite exposure through drinking water results in detrimental changes in the neuronal synapses, which may contribute to the arsenite-induced impairment of spatial memory.

Effect of selenium and vitamin e supplementation on plasma protein carbonyl levels in patients with arsenic-related skin lesions.

An estimated 35 million people in Bangladesh have been chronically exposed to arsenic in drinking water and are at risk of an array of adverse health conditions. The mechanisms of arsenic toxicity have not been well established; however, oxidative stress has been one commonly proposed pathway. In this study, we evaluated the effect of antioxidant supplementation on plasma protein oxidation among patients with arsenical skin lesions participating in a randomized double-blinded placebo-controlled trial of vitamin E and selenium. Subjects were randomized to 1 of 4 treatments arms (vitamin E, selenium, combination, or placebo) and were treated for a 6-mo period. We observed a dose-dependent increase in adjusted protein carbonyl levels by arsenic exposure status in the pretreatment samples, although trends were not statistically significant. Following the 6-mo intervention, there was a decrease in protein carbonyl levels in each treatment group, although no resultant decrease was significantly different from that seen in the placebo group. Although we did not see a notable effect of selenium or vitamin E supplementation on changes in protein carbonyl levels, these preliminary data demonstrate a feasible methodological approach for the assessment of plasma protein carbonyls in relation to environmental toxicants in a human population and their potential use as endpoints in intervention trials.

Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium toxicity.

Exposure to toxic metals has become an increasingly recognized source of illness worldwide. Both cadmium and arsenic are ubiquitous in the environment, and exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. The symptom picture of arsenic toxicity is characterized by dermal lesions, anemia, and an increased risk for cardiovascular disease, diabetes, and liver damage. Cadmium has a significant effect on renal function, and as a result alters bone metabolism, leading to osteoporosis and osteomalacia. Cadmium-induced genotoxicity also increases risk for several cancers. The mechanisms of arsenic- and cadmium-induced damage include the production of free radicals that alter mitochondrial activity and genetic information. The metabolism and excretion of these heavy metals depend on the presence of antioxidants and thiols that aid arsenic methylation and both arsenic and cadmium metallothionein-binding. S-adenosylmethionine, lipoic acid, glutathione, selenium, zinc, N-acetylcysteine (NAC), methionine, cysteine, alpha-tocopherol, and ascorbic acid have specific roles in the mitigation of heavy metal toxicity. Several antioxidants including NAC, zinc, methionine, and cysteine, when used in conjunction with standard chelating agents, can improve the mobilization and excretion of arsenic and cadmium.

Arsenic toxicity from homeopathic treatment.

UNLABELLED: Homeopathic medicine is commonly believed to be relatively harmless. However, treatment with improperly used homeopathic preparations may be dangerous. CASE REPORTS: Case 1 presented with melanosis and keratosis following short-term use of Arsenic Bromide 1-X followed by long-term use of other arsenic-containing homeopathic preparations. Case 2 developed melanotic arsenical skin lesions after taking Arsenicum Sulfuratum Flavum-1-X (Arsenic S.F. 1-X) in an effort to treat his white skin patches. Case 3 consumed Arsenic Bromide 1-X for 6 days in an effort to treat his diabetes and developed an acute gastrointestinal illness followed by leukopenia, thrombocytopenia, and diffuse dermal melanosis with patchy desquamation. Within approximately 2 weeks, he developed a toxic polyneuropathy resulting in quadriparesis. Arsenic concentrations in all three patients were significantly elevated in integument tissue samples. In all three cases, arsenic concentrations in drinking water were normal but arsenic concentrations in samples of the homeopathic medications were elevated. CONCLUSION: Arsenic used therapeutically in homeopathic medicines can cause clinical toxicity if the medications are improperly used.

Bladder cancer and arsenic exposure: differences in the two populations enrolled in a study in southwest Taiwan.

OBJECTIVE: Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 microg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought. METHODS: Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so. Underlying data for the Morales et al. study were obtained from the appendix to the NRC report. Bladder cancer mortality rates were calculated from case counts and person-years of observation for each study village. Villages were categorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source. RESULTS: The median village well arsenic levels ranged from 350 to 934 microg/L for villages solely dependent on artesian well water and from 10 to 717 microg/L for villages not solely dependent on artesian well water. Bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. Bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources. CONCLUSIONS: The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be explained either by arsenic acting as a high-dose carcinogen or in artesian well water as a co-carcinogen with some other aspect of artesian well water (possibly humic acid). Arsenic exposure level alone appears to be an insufficient exposure measure to describe the risk of bladder cancer mortality in the BFD-endemic area. Risk analyses that fail to take water source into account are likely to misrepresent the risk characterization, particularly at low arsenic levels.