Arsenic Toxicosis Research Articles

Comparative study of arsenic toxicosis and ocular pathology in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) breeding in arsenic contaminated areas of Yellowknife, Northwest Territories (Canada)

The Giant Mine is an abandoned gold mine in Yellowknife, Northwest Territories, Canada. Throughout its operation from 1948 to 2004, the Giant Mine released heavy amounts of arsenic trioxide into the environment, thus contaminating the soil and surface water within and around the vicinity of the mine site. Chronic arsenic (As) poisoning negatively impacts wildlife health and can induce multi-organ damages including neurodegeneration and visual dysfunction depending on concentration and duration of exposure. The aim of the current study was to comparatively assess retina layer changes and prevalence of ocular lesions in wild rodent populations (i.e. muskrats and red squirrels) breeding in arsenic endemic areas of Yellowknife, near the vicinity of the abandoned Giant mine site (∼2 km radius), at an intermediate location (approximately 20 km from the mine area) as well as a reference location (spanning 52–105 km from the city of Yellowknife, Canada). Eye globes were removed from euthanized muskrats and squirrels from the three sampling locations with increasing distance from the Giant mine area. Optical Coherence Tomography (OCT) was used to attempt a pan-retinal layer assessment, and histologic examination was utilized for assessment and confirmation of ocular lesions. The retinal layers were measured and statistically compared between the groups based on sampling locations to enhance the scope of histologic evaluations. The preliminary results revealed that thicknesses of ganglion cell layer (GCL), retina nerve fibre layer (NFL), and inner retina layer (IR) were statistically reduced in the muskrats from arsenic endemic area, particularly near the vicinity of the Giant mine compared to the control group. Generalized ocular pathology was histologically confirmed in all the muskrats from the arsenic endemic areas with the manifestation of moderate to severe lymphocytic plasmacytic uveitis (LPU), keratitis and subcapsular cataracts. Inner retinal degeneration was also observed in all the muskrats from the arsenic endemic areas, while muskrats from the control group were predominantly normal. Three muskrats from the control group were noted to have a mild LPU and keratitis. Significant histopathologic changes were not detected in the squirrel eyes from the three groups except for incidental mild cornea scars from all the locations. In general, these preliminary findings confirm the presence of ocular lesions and retina abnormalities in wild muskrats in the Yellowknife area and provide the first evidence of visual dysfunction and impairment in wildlife inhabiting arsenic endemic areas of Canada.

Experimental assessment of arsenic toxicity in garole sheep in India

Abstract Arsenic, a dangerous bio-accumulative poison, is a grave threat affecting a large number of people as well as animals throughout the World, particularly in Bangladesh and West Bengal, India. It is also a matter of concern as continuously entering into food chain through biotic and abiotic products. The present study was conducted to evaluate the experimental effect of arsenic toxicosis on Garole sheep of West Bengal. One group was subjected to oral arsenic exposure @ 6.6 mg Kg−1 over 133 days when rests considered as negative control. Periodical arsenic estimation in wool, urine and feces along with hemato-biochemical alteration were checked thoroughly. It was evident from the study that long term arsenic exposure exerted a significant (p

Effects of spirulina in arsenic poisoning in the Black Bengal goat

Some of the pharmacological properties of spirulina (Spirulina platensis) may be linked to its antioxidant potential, which mitigates oxidative stresses. In this study we examined whether spirulina mitigated arsenic-induced toxicity in the Black Bengal goat (Capra hircus). Nonpregnant female goats of approximately 12 months old were used in noninduced, nontreated control (T_1); arsenic-induced, nontreated (T_2); and arsenic-induced, spirulina-treated (T_3) groups. Groups T_2 and T_3 were given sodium arsenite orally (5 mg/kg) daily for 15 weeks. For therapeutic justification of spirulina, 1 group of arsenic-treated goats (T_3) was given spirulina at 0, 50, 100, and 150 mg/kg daily for another 15 weeks. At the end of the experiment, the goats were sacrificed. The arsenic-treated goats showed the highest arsenic accumulation in the kidneys, followed by the liver, lungs, skin, muscles, and heart. Histological analysis demonstrated fibrosis and lymphocyte infiltration in the liver, degeneration of tubular epithelia and hemorrhage in the kidneys, and keratin deposition in the skin. IgG- and IgM-bearing lymphocytes were unaffected in arsenic toxicosis. Spirulina treatment did not show any significant therapeutic effects on arsenic toxicosis in goat. Therefore, spirulina may not be effective in treating arsenic toxicosis in small animals such as goats.

Arsenic Toxicosis in Cattle: Meta‐Analysis of 156 Cases

Arsenic toxicosis is uncommon in cattle and successful treatment is rarely reported. This analysis reviews all cases of acute arsenic toxicosis in cattle reported in the literature and describes cases from Purdue University that had a favorable outcome. Clinical presentation of the disease, treatments, and variables associated with survival are described. One hundred and fifty-six cattle with arsenic toxicosis from 16 outbreaks. Meta-analysis. The most common clinical signs were sudden death (68%), diarrhea (33%), ataxia (29%), dehydration (22%), and respiratory distress (4%). The most common clinicopathologic abnormalities included azotemia (100%), hematuria (100%), increased liver enzyme activity (86%), and increased hematocrit (60%). One percent of cattle survived and the survival time for nonsurvivors ranged from 20 hours to 21 days. None of the clinical signs or clinicopathologic findings was associated with survival. Treatment was attempted in 24% of cases and was not associated with survival (P = .055), but administration of an antidote and administration of fluids were associated with better outcome (P = .036 and P = .009, respectively). In the animals presented to Purdue University, treatment with IV fluids and sodium thiosulfate resulted in decreased blood arsenic concentrations in all animals (P = .009) and a survival rate of 50%. Although acute arsenic toxicosis has a poor prognosis, survival is possible if aggressive fluid therapy and antidotes are administered.

Arsenic toxicosis in sheep: The first report from Iran

Arsenic contamination of groundwater has been previously reported in Ghopuz, a village located in the Northwest of Iran. Samples were taken from consuming and irrigation water and plants of the region for chemical analysis. A seven-year old ewe, which had lived in and fed a lifelong at the same place, with clinical signs such as weakness, wasting and inappropriate integument was necropsied. Grossly, buccal erosion, stomatitis, cutaneous ulcers and serous atrophy of fat deposits were observed. Rumen contents, wool and several tissue samples were obtained for toxicological and histopathological examinations. Mean arsenic concentration in the spring water, irrigation water and grass/algae were 70.11, 48.74 and 141.85 ppb (µg/kg), respectively. Arsenic levels were 486.73, 247.94, 127.92, 125.97 and 231.24 ppb in wool, skin, rumen contents, liver and kidney, respectively. Microscopic study revealed hyperemia and heavy parasitic infestation of the abomasal wall. Hyperemia and regeneration of renal tubule epithelia were observed in kidneys and hyperkeratosis, suppurative deep dermatitis and paniculitis were found in skin. Periacinar fibrosis and a poorly differentiated cholangiocarcinoma were seen in liver. In pancreas, reduced cell density of islands of Langerhans was noticeable. In the central nervous system, perineuronal and perivascular edema, ischemic changes in gray matter neurons, and microcavitation of white matter were present. Our findings confirmed chronic arsenic toxicosis in small ruminants in this region. It can be concluded that long-term consumption of arsenic contamined water and forage may be associated with chronic arsenic poisoning in domestic animals and human beings, with consequent neoplastic disease and induction of diabetes in this region.

Arsenic-induced nitrative DNA damage in human HaCaT keratinocytes

Arsenic is a most likely environmental carcinogenic species that poses a significant health risk in humans. Epidemiological evidence strongly implicates exposure to arsenic in the causation of human cancer of the skin, lung, and urinary bladder (IARC, 2004). Chronic exposure to arsenic leads to the development of lesions on the skin, including hyperkeratosis, hyperpigmentation and cancer. Dermatitis following the exposure to arsenic is a hallmark of the early stages of arsenic poisoning. In this study, we performed immunocytochemical method to examine the formation of 8-nitroguanine, a mutagenic DNA lesion formed during inflammation, in long term arsenic-treated spontaneously immortalized, non-tumorigenic human epidermal keratinocytes (HaCaT) cell line. When HaCaT cells were exposed chronically for 18 weeks to an environmentally relevant level of arsenic (0.05 ppm) in vitro, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. Arsenic induced 8-nitroguanine formation, inducible nitric oxide synthase (iNOS) and nuclear factor-kB (NF-kB) expression in the HaCaT keratinocytes and xenograft tumors. The staining intensity of 8-nitroguanine, iNOS, NF-kB and p53 in arsenic-treated cells was significantly greater than that in non-treated control at every twenty four days. These results suggest that arsenic can induce formation of 8-nitroguanine via iNOS expression, which may contribute to carcinogenesis. Therefore, the formation of nitrative DNA damage could be one of the mechanisms responsible for arsenic-induced carcinoma. 8-Nitroguanine could be a useful indicator of the risk of skin cancer development in response to chronic arsenic toxicosis.

Efficacy and toxicity of cymelarsan ® in Nubian goats infected with Trypanosoma evansi

Nine groups of Nubian goats were infected with T. evansi. Groups 1 and 2 were used as negative and positive control respectively, groups 3, 4, 5 and 6 were given a single intramuscular dose of Cymelarsan® at the rate of 0.125, 0.25, 0.625, 1.25 mg/kg, respectively. Goats in groups 7 and 8 were each given intramuscular Cymelarsan® at the rate of 0.125 mg/kg twice/week for two weeks and 0.125 mg/kg daily for 8 days, respectively. Goats in groups 9 and 10 were each given the drug intramuscular at the rate of 0.25 mg/kg twice/week for two weeks and 0.25 mg/kg daily for 8 days respectively. Goats in group 2 showed clinical signs of trypanosomosis while infected goats of groups (4 - 5) signs disappeared. Goats of group 3 responded to the treatment but relapse occurred. Goats of groups (6 - 10) were parasite free but expressed clinical signs of arsenic toxicosis. The haematological and serobiochemical changes were correlated with the clinical signs and pathology. Single dosages of 0.25 – 0.625 mg/kg wee recommended for treatment of T. evansi. Single dosage of 1.25 mg/kg and the multiple dosages were toxic and fatal. The drug has accumulative effect. Key words: Nubian goats, Cymelarsan, efficacy, toxicity, T. evansi, Sudan.

Arsenic in Herbal Kelp Supplements: Schenker et al. Respond

Arsenic in Herbal Kelp Supplements: Schenker et al. Respond

Elemental composition and diagenetic alteration of dinosaur bone: Distinguishing micron-scale spatial and compositional heterogeneity using PIXE

Proton Induced X-ray Emission (PIXE) analysis of thirteen Late Cretaceous (hadrosaurid, tyrannosaurid, and Tyrannosaurus) and Early Jurassic ( Dilophosaurus) dinosaur bones, two Late Cretaceous crocodylians, one plesiosaur, and three modern archosaurs ( Rhea and Caiman), documents micron-scale diagenetic patterns of elemental uptake and loss. PIXE detected Al, Si, P, S, Cl, K, Ca, Ba, Mn, Fe, Sr, Y, and Nd at levels > 1000 ppm; and Ti, Cr, Ni, Zn, As, Zr, and U at trace amounts < 1000 ppm. PIXE interrogation with a 1.5 μm diameter beam revealed a diagenetic pattern of significant Fe (180,000 ppm) and Mn (13,000 ppm) enrichment, with a corresponding loss of Ca and to a lesser degree P, within micron-scale regions in the Haversian system of compact dinosaur bone. Elemental composition of bone mineral immediately adjacent to the annuli surrounding a Haversian canal was depleted by approximately 90% in Fe and Mn, but showed a 50% increase in Ca ppm. Calcium levels in the fossils vary from 57% to 95% concentration of modern bone. Phosphorous levels in some dinosaur bone bioapatite are > 100% of modern. This enrichment may reflect the migration of Ca and P between the hydroxylapatite matrix and the surrounding sediment after death, resulting in early diagenetic loss followed by uptake and recrystallization on crystallite surfaces. The elemental composition of fossil bone from the Early Jurassic dinosaur Dilophosaurus is distinguished by elevated As ppm, generally not present in the Late Cretaceous dinosaurs. We suggest that As is adsorbed from the reductive dissolution of As-rich iron oxyhydroxides in the local aquifer and is not reflective of Mesozoic atmospheric conditions or arsenic toxicosis in dinosaurs. PIXE allows us to reaffirm that the histological structure, tissue density, and high surface area of the vascular canals of dinosaur Haversian bone affect postmortem elemental enrichment and depletion and to quantify these differences at scales as small as 1.5 μm.

Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats

Apoptosis or programmed cell death (PCD) is a genetically regulated cellular, physiological and biochemical suicidal mechanism that plays a crucial role in the development and defense of homeostasis, in which the cell participates in its own demise via a cascade of molecular interactions. PCD can be modulated by various stimuli including infectious agents or drugs. Arsenic is one among inducible toxic agent that triggers apoptosis via free radical generation. Since the generation of free radicals during the metabolism of arsenic is thought to be involved in arsenic toxicosis, understanding the deleterious effects caused by the ROS that attack the vital molecules like DNA has become important. The present work was conducted to evaluate the regulatory effect exerted by Vitamin C and Vitamin E upon the apoptotic process, which can be assessed by the presence of cells with apoptosis associated DNA breaks and characterize the role of TNF-α and caspase-3 in rats intoxicated with arsenic. Male albino rats of wistar strain (120–150 g) were used in this study and are further divided into seven groups. We observed that ascorbate and α-tocopherol selectively altered the extent of DNA damage by reducing TNF-α level and inhibiting the activation of caspase cascade, from these observations it is strongly believed that the present vitamins supplementation perspective, though observed in animal model, will have sustainable curative value among the already afflicted populations, neutralizing impact on freshly emerging arsenicosis scenario and possible proactive protection to those potentially susceptible to arsenicals exposure.

Determination of arsenic in dinosaur skeleton fossils by hydride generation atomic fluorescence spectrometry

Hydride generation atomic fluorescence spectrometry was for the first time utilized to determine trace toxic element arsenic in the skeleton fossils of four dinosaurs unearthed in Sichuan Province of China. The instrumental limit of detection (LOD) for arsenic was 0.03 μg/L under optimal experimental conditions, which compared favorably to that by ICP-AES and ETAAS. The samples were digested with aqua regia in boiling water bath. The recoveries of standard addition were found to be from 97 to 109%, and the analytical results were found in good agreement with those by ICP-AES. It is a simple, reliable, sensitive yet relatively inexpensive analytical method, compared to ICP-AES, ICP-MS or ETAAS. Interesting analytical results were found that the arsenic concentrations were all abnormally high in the skeleton fossils. The established analytical method and the analytical results may be helpful in revealing the mystery of the mass extinction of the dinosaur fauna. The analytical results, together with other data available to date, supported the argument that the arsenic toxicosis could be a contributing factor for the mass extinction of the dinosaur fauna in Sichuan Province of China.

Determination of arsenic in dinosaur skeleton fossils by hydride generation atomic fluorescence spectrometry

Hydride generation atomic fluorescence spectrometry was for the first time utilized to determine trace toxic element arsenic in the skeleton fossils of four dinosaurs unearthed in Sichuan Province of China. The instrumental limit of detection (LOD) for arsenic was 0.03 μg/L under optimal experimental conditions, which compared favorably to that by ICP-AES and ETAAS. The samples were digested with aqua regia in boiling water bath. The recoveries of standard addition were found to be from 97 to 109%, and the analytical results were found in good agreement with those by ICP-AES. It is a simple, reliable, sensitive yet relatively inexpensive analytical method, compared to ICP-AES, ICP-MS or ETAAS. Interesting analytical results were found that the arsenic concentrations were all abnormally high in the skeleton fossils. The established analytical method and the analytical results may be helpful in revealing the mystery of the mass extinction of the dinosaur fauna. The analytical results, together with other data available to date, supported the argument that the arsenic toxicosis could be a contributing factor for the mass extinction of the dinosaur fauna in Sichuan Province of China.

The prevalence of subjective symptoms after exposure to arsenic in drinking water in Inner Mongolia, China.

In Inner Mongolia, China, more than 300,000 people are chronically exposed to arsenic via their drinking water. We have previously reported that the prevalence of arsenical dermatosis was as high as 40% in the Hetao Plain area. However, the association between exposure to arsenic in drinking water and adverse health effects has not been fully examined. The purpose of this study was to examine the association between exposure to arsenic and prevalence of subjective symptoms. A cross-sectional study was carried out in 431 residents of an arsenic-affected village and 189 residents of an arsenic-free village in 1996. Health-related interviews and physical examinations were conducted. The odds ratio for each subjective symptom was estimated, comparing residents of arsenic-free and affected villages. An arsenic level of 50+ microg/L was found in 90.6% of wells in the arsenic-affected village. Adjusted odds ratios of subjective symptoms, including coughs (odds ratio [OR] = 12.8, 95% confidence interval [CI]: 6.4-25.6), stomachaches (OR = 5.8, 95% CI: 3.6-9.4), palpitations (OR = 3.6, 95% CI: 1.5-8.2), urination problems (OR = 14.7, 95% CI: 3.3-65.5) and spontaneous abortions (OR = 2.7, 95% CI: 0.8-8.4), were markedly higher amongst residents of the arsenic-affected village, including those without arsenic dermatosis. The present study shows a high prevalence of subjective symptoms amongst residents of an arsenic-affected village. Symptoms occurred in people with and without arsenic dermatosis. Our findings suggest that symptoms other than dermatosis should be considered when a clinical diagnosis of arsenic toxicosis is made.

Acute Arsenic Toxicosis in Five Horses

Five adult horses presented with acute clinical signs of watery diarrhea, excessive salivation, muscle tremors, ataxia, and depression. Four died within 24 hours and the fifth was euthanatized approximately 48 hours after onset of clinical signs. Necropsy finds in two of the horses included hyperemia of gastric mucosa, intestines filled with green to black watery fluid, and multifocal to coalescing, hemorrhagic 1.0-2.0-cm-diameter ulcers of the mucosa of the cecum and large colon. Histopathologic changes in the cecum and large colon consisted of mucosal necrosis and ulceration, vascular thrombosis, necrosis of submucosal blood vessels, and infiltration by mixed mononuclear inflammatory cells and neutrophils. Arsenic toxicosis was suspected. The owner had not been feeding the horses any grain; however, a mixture of grain and pink powder was found in the pasture. Liver arsenic concentrations in the two horses were 14.0 and 11.0 ppm, a sample of renal cortex contained 108 ppm arsenic, and the grain/powder mixture found in the pasture was positive for arsenic at > 3,000 ppm. kidney lead concentrations were 6.5 and 4.2 ppm. Results were consistent with lead arsenate or lead arsenite poisoning.

On the Lennox Syndrome with the Onset in Puberty

The cases of the Lennox syndrome which began at the age between 14 and 16, namely in puberty, were reported. The first case, a 22-year-old woman, was attacked with grand mal seizure at the age of 15, and one year later "Juchzer" (ref. Doose) appeared. This continued for two years, and then astatic seizures appeared. The second case, a 20-year-old woman, was attacked with grand mal seizure at the age of 14, and soon after astatic seizure appeared. Thus both are closely related with grand mal seizures. The first case is idiopathic, and the intelligence developed normally till the onset of the Lennox syndrome. but after that it became disturbed. The second case is residual state of arsenic toxicosis, and so the intelligence was already disturbed before the onset. On EEG both of them at first showed diffuse slow waves of high voltage, and in several years after the appearance of the Lennox syndrome, slow spike-waves were found. On therapy, scarcely no beneficial effects were noted by conventional antiepileptics, and by nitrazepam only the temporal beneficial effect was obtained. The symptoms of our cases are generally similar to the Lennox syndrome in infancy. Though we observed only two cases, we presented our cases as the Lennox syndrome with late onset.