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PubMed2000

The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells.

It is accepted that inorganic arsenic trioxide is an inducer of apoptosis for many types of cancer. Our previous studies have demonstrated that arsenic trioxide induces apoptosis of esophageal carcinoma cells. Administration of arsenic trioxide results in the inhibition of growth and survival of tumor cells. Esophageal carcinoma cells treated with arsenic trioxide for 3 days demonstrated a typical morphological appearance of apoptosis. To further examine molecular mechanism of arsenic trioxide induced apoptosis of esophageal carcinoma cells, we have investigated the early changes of the apoptotic cell induced by arsenic trioxide. Our results indicated that arsenic trioxide induced apoptosis of esophageal carcinoma cells occurs as early as 2 h after treatment. Annexin-v staining has further proved that the phosphatidylserine is exposed at 2 h. The early morphological change of arsenic trioxide treated cells was in the mitochondria. Arsenic trioxide treated cells displayed aggregated mitochondria. It induces accumulation of high electron-density amorphous substances, swollen and disruption of mitochondria in oesophageal carcinoma cells after 2 h treatment. The alteration of mitochondria induced by arsenic trioxide seems to occur before the condensation of chromatin. Thus, our data demonstrated that the primary target of arsenic trioxide induced apoptosis of esophageal carcinoma cells may be the mitochondria. It is possible that arsenic trioxide is a mitochondriotoxic agent.

Antineoplastic Agents↗
PubMed2004

Arsenic induced inhibition of delta-aminolevulinate dehydratase activity in rat blood and its response to meso 2,3-dimercaptosuccinic acid and monoisoamyl DMSA.

OBJECTIVE: The objective of this study was to investigate arsenic induced changes in blood delta-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. METHODS: Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. RESULTS: In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value. CONCLUSIONS: The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Administration, Oral↗
PubMed2002

Developmental changes in inhibitory effects of arsenic and heat shock on growth of pre-implantation bovine embryos.

Although sensitive to various disrupters, pre-implantation embryos possess some cellular cytoprotective mechanisms that allow continued survival in the face of a deleterious environment. For stresses such as heat shock, embryonic resistance increases as development proceeds. Present objectives were to determine whether (1) arsenic compromises development of pre-implantation bovine embryos, (2) developmental changes in embryonic resistance to arsenic mimic those seen for resistance to heat shock, and (3) developmental patterns in induction of apoptosis by arsenic are correlated with similar changes in resistance of embryos to inhibitory effects of arsenic on development. Bovine embryos produced by in vitro fertilization were exposed at the two-cell stage or at day 5 after insemination (embryos > or = 16-cells in number) to either sodium arsenite (0, 1, 5, or 10 microM) or heat shock (exposure to 41 degrees C for 0, 3, 4.5, 6, or 9 hr). Arsenic induced apoptosis and increased group 2 caspase activity for embryos at the > or = 16-cell stage, but not for embryos at the two-cell stage. In contrast to these developmental changes in apoptosis responses, exposure to arsenic reduced cell number 24 hr after exposure for both two-cell embryos and embryos > or = 16-cells. Similarly, the percentage of embryos that developed to the blastocyst stage at day 8 after fertilization was reduced by arsenic exposure at both stages of development. Heat shock, conversely, reduced development to the blastocyst stage when applied at the two-cell stage, but not when applied to embryos > or = 16-cells at day 5 after insemination. In conclusion, arsenic can compromise development of bovine pre-implantation embryos, the temporal window of sensitivity of embryos to arsenic is wider than for heat shock, and cellular cytoprotective responses that embryos acquire for thermal resistance are not sufficient to cause increased embryonic resistance to arsenic exposure. It is likely that despite common cellular pathologies caused by arsenic and heat shock, arsenic acts to reduce development in part through biochemical pathways not activated by heat shock. Moreover, the embryo does not acquire significant resistance to these perturbations within the time frame in development examined.

Animals↗
PubMed1994

Effect of arsenic exposure on alveolar macrophage function. I. Effect of soluble as(III) and as(V).

Despite potential differences in the mechanism and potency of toxicity between the two common oxidation states of arsenic (As(III) and As(V)), assessments of the risk from inhaled arsenic generally ignore the oxidation state of inorganic arsenicals. Differences between potency and toxicity of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure to soluble arsenic. Male Sprague-Dawley rats were used throughout. One day following intratracheal instillation of 1 mg/ml (as arsenic) of either sodium arsenite (As(III)) or sodium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O2-), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF-alpha) production. There were no differences in bronchoalveolar lavage fluid PGE2 or TNF-alpha. PAM lavaged from As(V)-exposed animals showed significant increases in O2- production. In vivo exposure to either oxidative form of arsenic decreased basal and lipopolysaccharide (LPS)-induced release of TNF-alpha production by PAM, but did not suppress LPS-induced production of PGE2. To test the direct effects of arsenic on PAM function, PAM were lavaged from control animals and exposed, in vitro, to either arsenical for up to 24 hr to concentrations of 0.1 to 300 micrograms/ml arsenic. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased, even at the highest dose. Significant dose-dependent inhibition of O2- production was only evident after 24 hr exposure to arsenicals. As(III) was more potent than As(V), inhibiting O2- at concentrations as low as 0.1 micrograms/ml compared to 1.0 micrograms/ml of As(V). Suppression of LPS-induced release of TNF-alpha also occurred at lower concentrations of As(III), 50% inhibition at 0.15 micrograms/ml, compared to As(V), 50% inhibition at 1.8 micrograms/ml. While As(III) exposure had no affect on PGE2 production, As(V) caused inhibition of LPS-induced PGE2 production at concentrations above 1.0 micrograms/ml. Differences between As(III) and As(V) indicate that different mechanisms and/or potencies exist between the two arsenic species. Arsenic-induced alteration in PAM function may compromise host defense against infections and alter immune surveillance.

Animals↗
PubMed1993

Essential trace elements in humans. Serum arsenic concentrations in hemodialysis patients in comparison to healthy controls.

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n = 85) and of healthy controls (n = 25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5 +/- 1.8 ng/mL vs 10.6 +/- 1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.

Arsenic↗
PubMed2004

Bioaccumulation of arsenic in marine fish and invertebrates from Alaska and California.

Past studies determined that concentrations of arsenic in the liver of flathead sole from Alaska were generally higher than those found in fish from other locations sampled along the west coast of the United States (Meador et al. 1994). A study was conducted to examine arsenic concentrations and patterns of bioaccumulation in fish and potential prey species from two geographic locations. Flathead sole were collected from four sites in the Gulf of Alaska and white croaker and English sole were collected from five sites in California. Potential prey species from each site were also examined and found to contain high concentrations of arsenic. In California, the sites with the lowest sediment concentrations of arsenic, total organic carbon, and acid-volatile sulfides (AVS) contained invertebrates with the highest tissue concentrations. Regression analysis determined that arsenic in polychaetes was highly correlated to sediment concentrations of arsenic normalized to AVS but was higher overall for the California samples. Even though invertebrates from several of the California sites exhibited much higher concentrations of arsenic than invertebrates from the Alaska sites, liver and muscle tissue from flathead sole collected in Alaska usually exhibited higher concentrations than fish from the California sites. When concentrations of arsenic in fish liver were plotted against concentrations of arsenic in sediment normalized to AVS levels, a very high correlation was obtained for all sites. This suggests that AVS, or some factor correlated with AVS, may have been responsible for controlling arsenic bioaccumulation in these fish species through dietary uptake and exposure to arsenic in water. Based on the available data, it appears that dietary uptake may be related to fish tissue concentrations, but uptake of aqueous arsenic may be responsible for the higher tissue concentrations in fish from Alaska.

Alaska↗
PubMed2005

Environmental geochemistry study of arsenic in Western Hunan mining area, P.R. China.

The geochemical characteristics of arsenic in the soil of the Western Hunan mining area of P.R. China were systematically studied. The results show that the strata of Western Hunan are rich in arsenic and that Western Hunan is a geochemically abnormal region for arsenic. The experimental study on speciation in the strata also indicates that the speciation of arsenic in the Neoproterozoic-Cambrian strata are mainly easily transferred speciation (exchangeable, carbonate-bound, sulfides-bound), which are approaching or exceed 60%. Arsenic content in the main soil of Western Hunan is in the range of 8.8-22.8 mug g(-1), the mean value is 16.1 mug g(-1), which is larger than the arsenic background value of Hunan soil. The distribution of rock with high arsenic content or high easily transferred arsenic speciation is consistent with the distribution of high arsenic content soil. In the mining region, part soils and river/brook waters were polluted by mine tailings and mining/smelting waste water. The arsenic content in polluted paddy soils and river/brook water is 46.26-496.19 microg g(-1), 0.3-16.5 mgL(-1), respectively. The positive abnormality and pollution of arsenic in the soil and water affects the arsenic content of the crop and the inhabitants' health.

Arsenic↗
PubMed2005

Arsenic in groundwaters of the Lower Mekong.

Increasing incidence and awareness of arsenic in many alluvial aquifers of South-east Asia has raised concern over possible arsenic in the Lower Mekong Basin. Here, we have undertaken new research and reviewed many previous small-scale studies to provide a comprehensive overview of the status of arsenic in aquifers of Cambodia and the Cuu Long Delta of Vietnam. In general natural arsenic originates from the Upper Mekong basin, rather than from the local geology, and is widespread in soils at typical concentrations of between 8 and 16 ppm; (dry weight). Industrial and agricultural arsenic is localised and relatively unimportant compared to the natural alluvial arsenic. Aquifers most typically contain groundwaters of no more than 10 microg L(-1), although scattered anomalous areas of 10 to 30 microg L(-1 )are also quite common. The most serious, but possibly ephemeral arsenic anomalies, of up to 600 microg L(-1), are associated with iron and organic-rich flood-plain sediments subject to very large flood-related fluctuations in water level, resulting in transient arsenopyrite dissolution under oxidizing conditions. In general, however, high-arsenic groundwaters result from the competing interaction between sorption and dissolution processes, in which arsenic is only released under reducing and slightly alkaline conditions. High arsenic groundwaters are found both in shallow water-tables, and in deeper aquifers of between 100 and 120 m depth. There is no evidence of widespread arsenicosis, but there are serious localised health-hazards, and some risk of low-level arsenic ingestion through indirect pathways, such as through contaminated rice and aquaculture. An almost ubiquitous presence of arsenic in soils, together with the likelihood of greatly increased groundwater extraction in the future, will require continuing caution in water resources development throughout the region.

Aluminum↗
PubMed1988

Chemical speciation and distribution of arsenic in water, suspended solids and sediment of Xiangjiang River, China.

The forms of arsenic in the Zuzou Zone of the Xiangjang River are evaluated. Nine fractions of arsenic, consisting of soluble arsenic(III) and total soluble arsenic, loosely bound arsenic, aluminium arsenate, iron arsenate, calcium arsenate, arsenic occluded on iron oxide, organic compounds of arsenic and residual arsenic, were separated from suspended solids and sediments by sequential chemical extraction. All arsenic fractions were determined by ASV and AFS. The distributions of arsenic and arsenic fractions in water, sediments and suspended solids are discussed in terms of the mechanisms of arsenic transport and deposition in aquatic ecosystems.

Arsenic↗
PubMed2006

Mapping of spatial multi-scale sources of arsenic variation in groundwater on ChiaNan floodplain of Taiwan.

This study applied multivariate factorial kriging to derive the characteristics of the spatial variations of groundwater arsenic distributions at different scales on the ChiaNan floodplain, Taiwan. Seven variables (dissolved oxygen, oxidation-reduction potential, alkalinity, sulfate, iron cations, manganese cations and total organic carbon) and Arsenic were adopted to analyze the mechanisms of arsenic enrichments in groundwater. The hydrogeological environment had spatial and quantitative influences on arsenic enrichments at different scales. The regional scale was set to 32 km referring to the extension distance of flow paths to reflect the effects of flushing in the aquifer, while the local scale was set to 16 km referring to the farthest distance of seawater intrusion to determine the influence of seawater intrusion. The results of factorial kriging suggested that arsenic releases resulted partially from pyrite oxidation during the flushing at the regional scale and partially due to the siderite dissolution at the local scale. Overall, the alkalinity dominated arsenic distribution in groundwater at both the regional and local scales. The multivariate factorial kriging results also demonstrated that seawater intrusion slightly affected the increase of arsenic in groundwater, accounting for only 17.3% of total variation. However, the interaction of seawater intrusion and arsenic distribution in space indicated that seawater intrusion restrained the distribution of arsenic from the areas where seawater was located. High dissolved oxygen was found at where over-pumping induced drawdown cones occurred and also limited the spatial variation of arsenic. Our findings indicate that multivariate factorial kriging can be a useful mapping tool to improve understanding of the mechanism of arsenic release in groundwater at different scales. And the results conducted from the application of multivariate factorial kriging in southwestern Taiwan reveal the important influences of the hydrogeological processes, either artificial or natural, on the arsenic variations in groundwater.

Arsenic↗
PubMed2006

The source of naturally occurring arsenic in a coastal sand aquifer of eastern Australia.

The discovery of dissolved arsenic in a coastal aquifer used extensively for human consumption has led to widespread concern for its potential occurrence in other sandy coastal environments in eastern Australia. The development of an aquifer specific geomorphic model (herein) suggests that arsenic is regionally derived from erosion of arsenic-rich stibnite (Sb(2)S(3)) mineralisation present in the hinterland. Fluvial processes have transported the eroded material over time to deposit an aquifer lithology elevated in arsenic. Minor arsenic contribution to groundwater is derived from mineralised bedrock below the unconsolidated aquifer. An association with arsenic and pyrite has been observed in the aquifer in small discrete arsenian pyrite clusters rather than actual acid sulfate soil horizons. This association is likely to influence arsenic distribution in the aquifer, but is not the dominant control on arsenic occurrence. Arsenic association with marine clays is considered a function of their increased adsorptive capacity for arsenic and not solely on the influence of sea level inundation of the aquifer sediments during the Quaternary Period. These findings have implications for, but are not limited to, coastal aquifers. Rather, any aquifer containing sediments derived from mineralised provenances may be at risk of natural arsenic contamination. Groundwater resource surveys should thus incorporate a review of the aquifer source provenance when assessing the likely risk of natural arsenic occurrence in an aquifer.

Arsenic↗
PubMed2004

Arsenic contamination awareness among the rural residents in Bangladesh.

Arsenic poisoning of tubewell water, which constitutes the primary source of drinking water, has become the greatest health threat to the people of rural Bangladesh. Somewhere between 35 to 57 million people in the country are now suspected of being affected by drinking water contaminated with arsenic. While the Bangladesh government, non-government organizations (NGOs), and bilateral and multilateral assistance agencies are involved in combating this dreadful problem, all of their efforts to date have proceeded without having grassroots information about arsenic poisoning. The objectives of this study are to investigate the level of knowledge rural residents have regarding arsenic poisoning and to identify the correlates of that knowledge. Questionnaire surveys administered among residents of four rural areas in Bangladesh provided the major data source for this study. Twenty villages were selected from moderate and low arsenic risk regions and a total of 356 respondents, 177 from medium risk regions and 179 from low risk regions, were interviewed. Analysis of the survey data reveals that arsenic awareness is currently not widespread in the study villages, particularly in the low arsenic risk region. There are also gaps in arsenic knowledge regarding the diseases caused by arsenic poisoning and mitigating measures available to prevent contamination. This study identified arsenic risk region, level of education, gender, and age as important determinants of arsenic knowledge. The findings of this study will aid in making existing health education programs more effective and in reducing the risk of developing arsenic-related illnesses.

Arsenic↗
PubMed2006

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice.

The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic.

Animals↗
PubMed2005

Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat.

Impaired antioxidant defense mechanisms and oxidative stress are implicated in the pathogenesis of arsenic toxicity. Our study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (70 mg/kg body weight) once daily for 60 days along with arsenic (100 ppm sodium arsenite mixed in drinking water) would prevent arsenic-induced changes in antioxidant defense system, superoxide dismutase (SOD-total SOD, Mn SOD, Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in rat brain regions such as cortex, hypothalamus, striatum, cerebellum and hippocampus. The present study also examined the effect of alpha-lipoic acid over arsenic-induced oxidant production and lipid peroxidation level (LPO) in discrete brain regions of rats. The cortex, striatum and hippocampus showed greater decreases in GSH-Px enzyme activity than cerebellum and hypothalamus with arsenic exposure. Striatum had the greatest percentage of decreased activities of total SOD and Mn SOD, whereas cortex had the greatest percentage decrease in the activity of Cu/Zn SOD in arsenic-alone treated rats. Hypothalamus and cerebellum exhibited the lowest catalase activity among all tested regions in arsenic-only treated rats. Rate of dichlorofluorescin oxidation, an indication of reactive oxygen species and other intracellular oxidants production was increased with arsenic exposure in all brain regions studied. Cortex, hippocampus and striatum exhibited greater increase of LPO levels than cerebellum and hypothalamus. SOD, CAT, GSH-Px activities were upregulated in arsenic plus lipoic acid treated versus arsenic-only treated rats. Also, simultaneous lipoic acid treatment along with arsenic proved to be sufficient in reducing oxidant production and LPO level in all rat brain regions. Our results demonstrate that arsenic-induced deficits in antioxidant enzyme activities and increase in oxidant production and lipid peroxidation level in brain regions can be overcome through simultaneous treatment with lipoic acid.

Animals↗
PubMed2003

A methodological approach for the identification of arsenic bearing phases in polluted soils.

A methodological approach is used to characterize arsenic pollution in three soils and to determine arsenic speciation and association with solid phases in three polluted soils. HPLC-ICP-MS was used for arsenic speciation analysis, SEM-EDS and XRD for physical characterization of arsenic pollution, and sequential chemical extractions to identify arsenic distribution. Arsenic was concentrated in the finest size fractions also enriched in iron and aluminium. Total arsenic concentrations in soils are close to 1%. Arsenic was mainly present as arsenate, representing more than 90% of total arsenic. No crystallised arsenic minerals were detected by XRD analysis. SEM-EDS observations indicated arsenic/iron associations. Modified Tessier's procedure showed that arsenic was mainly extracted from amorphous iron oxide phase. The results of this methodological approach lead to predict the formation of iron arsenates in the case of one of the studied soils while arsenic sorption on iron amorphous (hydr)oxides seemed to be the determinant in the two other soils.

Arsenicals↗
PubMed2002

Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants.

Epidemiological studies on arsenic contamination in drinking water indicated presence of arsenic in fetal tissues. Experiments on human fetal brain explants on exposure to arsenic in culture showed disturbance in lipid peroxidation, generation of nitric oxide (NO), reactive oxygen species (ROS) and apoptosis. The oxidative stress challenged by antioxidant vitamins C, E or chelator dimercaptosuccinic acid (DMSA) may reverse arsenic toxicity on neuronal development. The concept was tested with the models: (A) human fetal brain explants exposed to arsenic, 0.3 mg/l in culture for 24 h; (B) rat neonatal brain explants from 1-day-old litters exposed to 0.3 mg/l arsenic in drinking water during gestation. Rats (n=10) were given oral administration of vitamin C, 2.5 mg/kg/day, vitamin E, 148 microg/kg/day during gestation and DMSA, 50 mg/kg for 2 days at the end of gestation. (A) The arsenic induced in human fetal brain explants increase in production of NO, 20% and ROS, 25%, and decrease in DNA, 62% and protein, 54% synthesis. The morphological analyses showed growth of viable cells, neural networking vis-à-vis apoptosis on exposure to arsenic for 24 h and necrosis and loss of ground matrix on arsenic exposure for 18 days. The occurrence of two processes of apoptosis and necrosis in different neurons of same culture indicated existence of a selective cellular defense against arsenic toxicity. (B) The rats exposed to arsenic showed increased generation of NO, 25% and ROS, 22%, loss of glutathione content from 42 to 35 microg/mg protein, 40% increase in lipid peroxidation and decreased superoxide dismutase at 32%. The administration of vitamins C, E and DMSA showed partial reversal of the effects indicating possible protection from arsenic toxicity.

Animals↗
PubMed1997

Relationship of urinary arsenic to intake estimates and a biomarker of effect, bladder cell micronuclei.

The purpose of this study was to investigate methods for ascertaining arsenic exposure for use in biomarker studies. Urinary arsenic concentration is considered a good measure of recent arsenic exposure and is commonly used to monitor exposure in environmental and occupational settings. However, measurements reflect exposure only in the last few days. To cover longer time periods exposure can be estimated using arsenic intake data, calculated by combining measures of environmental arsenic and inhalation/ingestion rates. We compared these different exposure assessment approaches in a population chronically exposed to arsenic in drinking water in northern Chile. The study group consisted of 232 people, some drinking water low in arsenic (15 micrograms/l) and others drinking water with high arsenic concentrations (up to 670 micrograms/l). First morning urine samples and questionnaire data, including fluid intake information, were collected from all participants. Exfoliated bladder cells were collected from male participants for the bladder cell micronuclei assay. Eight different indices of exposure were generated, six based on urinary arsenic (microgram As/l urine; microgram As/g creatinine; microgram InAs/l urine; microgram MMA/l urine; microgram DMA/l urine; microgram As/h, excreted), and two on fluid intake data (microgram As/day, ingested; microgram As/l fluid ingested-day). The relationship between the different exposure indices was explored using correlation analysis. In men, exposure indices were also related to a biomarker of effect, bladder cell micronuclei. While creatinine-adjusted urinary arsenic concentrations had the strongest correlations with the two intake estimates (r = 0.76, r = 0.81), unadjusted urinary arsenic showed the strongest relationship with bladder cell micronuclei. These data suggest that, in the case of the bladder, unadjusted urinary arsenic concentrations better reflect the effective target organ dose compared to other exposure measures for biomarker studies.

Adolescent↗
PubMed2000

Speciation of key arsenic metabolic intermediates in human urine.

Biomethylation is the major human metabolic pathway for inorganic arsenic, and the speciation of arsenic metabolites is essential to a better understanding of arsenic metabolism and health effects. Here we describe a technique for the speciation of arsenic in human urine and demonstrate its application to the discovery of key arsenic metabolic intermediates, monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), in human urine. The study provides a direct evidence in support of the proposed arsenic methylation pathway in the human. The finding of MMAIII and DMAIII in human urine, along with recent studies showing the high toxicity of these arsenicals, suggests that the usual belief of arsenic detoxification by methylation needs to be reconsidered. The arsenic speciation technique is based on ion pair chromatographic separation of arsenic species on a 3-micron particle size column at 50 degrees C followed by hydride generation atomic fluorescence detection. Speciation of MMAIII, DMAIII, arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in urine samples is complete in 6 min with detection limits of 0.5-2 micrograms/L. There is no need for any sample pretreatment. The capability of rapid analysis of trace levels of arsenic species, which resulted in the findings of the key metabolic intermediates, makes the technique useful for routine arsenic speciation analysis required for toxicological and epidemiological studies.

Arsenic↗