Showing papers on "Sodium arsenite published in 1998"
TL;DR: It is concluded that the MAP kinases ERK and p38 are involved in the induction of heme oxygenase-1, and that at least one AP-1 element is involved in this response.
259 citations
TL;DR: The specific activity of this critical enzyme for arsenite biotransformation was determined by incubating liver, testis, kidney, or lung cytosol of male B6C3F1 mice with sodium arsenite and S-[methyl-3H]adenosyl-L-methionine and measuring the formation of [methyl- 3H]monomethylarsonate.
106 citations
Journal Article•
TL;DR: The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells.
Abstract: Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as sodium arsenite, sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells.
106 citations
TL;DR: The changes described here could contribute to vascular occlusion, ischemia, and tissue death associated with arsenic circulatory disorders.
Abstract: Chronic arsenic exposure is associated with alterations in peripheral circulation and vascular disease Toxicity to the vasculature is documented, but the effect of arsenic on the erythrocyte has not been evaluated To determine if arsenic was toxic to human erythrocytes and whether this could contribute to vascular disease, human erythrocytes were incubated in vitro with sodium arsenate, As(V), or sodium arsenite, As(III), and assessed for damage After 5 h of incubation with 10 mM As(V) or As(III), significant cell death (hemolysis) only occurred in the As(V) treated cells Morphologic changes were assessed by scanning electron microscopy and light microscopy As(V) induced a classic discocyte-echinocyte transformation extending to the formation of sphero-echinocytes; these changes were concentration dependent As(III) treatment also resulted in echinocyte formation but less extensive than in As(V) treated cells, and no sphero-echinocytes were formed The observed damage was consistent with reported changes induced by ATP depletion, and measurement of ATP in these samples confirmed this as a mechanism of damage As(V) treatment at concentrations as low as 001 mM for 5 h significantly depleted ATP, and As(III) was relatively ineffective in causing ATP depletion Based on these three parameters, the erythrocyte was estimated to be as much as 1000 times more susceptible to As(V) than As(III) ATP is required for the cell to maintain membrane integrity and deform efficiently in circulation The changes described here could contribute to vascular occlusion, ischemia, and tissue death associated with arsenic circulatory disorders
87 citations
TL;DR: It is reported that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines, and results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.
Abstract: Arsenical compounds, known to be human carcinogens, were shown to disturb cell cycle progression and induce cytogenetic alterations in a variety of cell systems. We report here that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35% of the total cell population was arrested at the mitotic stage after treatment with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells. Under a microscope, we observed abnormal mitotic figures in arsenite-arrested mitotic cells, including deranged chromosome congression, elongated polar distance of mitotic spindle, and enhanced microtubule immunofluorescence. The spindle microtubules of arsenite-arrested mitotic cells were more resistant to nocodazole-induced dissolution than those of control mitotic cells. According to turbidity assay, arsenite at concentrations below 100 microM significantly enhanced polymerization of tubulins. Since spindle dynamics play a crucial role in mitotic progression, our results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.
78 citations
TL;DR: Results indicated that signal transduction involving tyrosine kinase rather than the MAPK family regulates the induction of human HO-1 gene expression by stress inducers.
Abstract: The effect of a tyrosine kinase inhibitor, herbimycin A, on the induction of heme oxygenase-1 (HO-1) mRNA in HeLa cells upon exposure to hemin, sodium arsenite and cadmium chloride was examined. The induction of HO-1 mRNA by hemin was inhibited when the cells were pretreated with herbimycin A. Herbimycin also inhibited arsenite- and cadmium-dependent induction of HO-1 mRNA in a dose-dependent manner, but less inhibition was observed in cadmium-treated cells than in ones treated with hemin- or arsenite. Genistein (50 microM), another tyrosine kinase inhibitor, also inhibited the induction of HO-1 mRNA by hemin, arsenite, and cadmium. Nuclear runoff assays revealed that herbimycin blocked the hemin-induced transcription of the HO-1 gene. The induction of HO-1 mRNA by hemin in human peripheral blood mononuclear cells was inhibited by herbimycin. The tyrosine phosphorylation of a protein with a molecular mass of 66 kDa in the cells was increased by hemin- or arsenite-treatment, and this increase was inhibited by treatment with 5 microM herbimycin. When HeLa cells were treated with a specific inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase cascade, PD58059 (100 microM), suppression of the cadmium-dependent HO-1 induction was not observed, but the hemin- or arsenite-dependent induction was slightly inhibited. SB203580, an inhibitor of p38 MAPK, did not affect the HO-1 induction. These results indicated that signal transduction involving tyrosine kinase rather than the MAPK family regulates the induction of human HO-1 gene expression by stress inducers.
63 citations
TL;DR: The data suggest that exogenous nitric oxide can block stress-induced endothelial cell apoptosis in vitro and are consistent with the hypothesis that inhibitors of NF-kappaB DNA binding activity are associated with protection against apoptosis-inducing stimuli.
Abstract: OBJECTIVES To determine a mechanism by which nitric oxide alters induction of stress-induced endothelial cell apoptosis in vitro. Apoptosis is a form of cellular suicide that has been implicated in the pathogenesis of multiple organ dysfunction syndrome. DESIGN Prospective, controlled trial. SETTING Research laboratory of a large, academic medical center. SUBJECTS Cultured primary porcine aortic endothelial cells. INTERVENTIONS Cells were treated with a range of doses of agents that either spontaneously generate nitric oxide (S-nitroso-N-acetyl-D,L-penicillamine [SNAP] or (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate [DETA-NO]) or block nitric oxide production (Nomega-methyl-L-arginine [L-NMA]). The ability of these agents to alter the rate of cell death by apoptosis (induced by the sequence stimuli lipopolysaccharide [LPS] followed by sodium arsenite) was measured. Mechanistic studies included examining the ability of: a) nitric oxide "donors" to alter nuclear factor kappa B (NF-kappaB) DNA binding activity and the level of IkappaBalpha accumulation; and b) a stable cyclic guanosine monophosphate (cGMP) analog (8-bromo-cGMP) to mimic the effect of nitric oxide donors. MEASUREMENTS AND MAIN RESULTS The sequence LPS/sodium arsenite increased the rate of endothelial cell apoptosis (47.4%, p< .05 vs. control), as measured by fluorescent-activated cell scanning using annexin V/propidium iodide staining. DETA-NO generated nitric oxide (as indicated by an increase in the concentration of the stable end-products of nitric oxide metabolism) and decreased the rate of endothelial cell apoptosis (20.6% at a dose of 2 mM, p=.0001 vs. control). DETA-NO also decreased NF-kappaB DNA binding activity and the apparent accumulation of its endogenous inhibitor, IkappaBalpha. The 8-bromo-cGMP did not mimic the effects of nitric oxide donors (DETA-NO) on apoptosis. CONCLUSIONS These data suggest that exogenous nitric oxide can block stress-induced endothelial cell apoptosis in vitro. The mechanistic studies are consistent with our hypothesis that inhibitors of NF-kappaB DNA binding activity are associated with protection against apoptosis-inducing stimuli. The results do not support a role for cGMP in mediating the protective effect of DETA-NO in our model.
56 citations
TL;DR: A hydride cold-trapping technique was developed and optimised for the measurement of urinary arsenic metabolites and up to two fold increases of urinary ASi excretion in rats compared with control rats were also observed in animals dosed with various forms of arsenicals.
Abstract: A hydride cold-trapping technique was developed and optimised for the measurement of urinary arsenic metabolites. The analytical precision of the method was found to be 6.1, 4.0 and 4.8% (n = 5) for inorganic arsenic (Asi), monomethylarsonate (MMA) and dimethylarsinate (DMA), respectively, with recoveries close to 100%. The detection limits were 1.0, 1.3 and 3 ng for Asi, MMA and DMA, respectively. The method was then used to analyse urine samples obtained from three groups of workers for occupational exposure in three companies where copper chrome arsenate was used for timber treatment. The results were compared with those for a normal control group of laboratory workers. Arsenic and its metabolites were also measured in experimental rats given 5 mg As kg–1 body mass by oral gavage in the form of sodium arsenite, calcium arsenite or sodium arsenate. Occupational workers showed a significantly higher excretion of Asi. Up to two fold increases of urinary Asi excretion in rats compared with control rats were also observed in animals dosed with various forms of arsenicals. The method is suitable for the measurement of arsenic metabolites in urine of both humans and experimental animals.
52 citations
TL;DR: The 'retention analysis method', which is based on size-exclusion chromatography (SEC) in conjunction with an arsenic-specific detector (graphite furnace atomic absorption spectrometer, GFAAS), was used to study the effect of pH, temperature and concentration on the formation of arsenic-glutathione species after injection of sodium arsenite using phosphate-buffered saline solutions as mobile phases.
46 citations
TL;DR: Direct effects of low-level arsenic exposure on immune function of cotton rats was minimal and may not be clinically relevant with regard to susceptibility to disease in the wild, however, malnutrition caused by decreased food intake may eventually lead to atrophy of lymphoid organs and render animals more susceptible to environmental pathogens.
Abstract: Arsenic is a ubiquitous contaminant of many toxic waste sites around the country and experimental animal trials have indicated that arsenic may be immunotoxic to laboratory rodents. Because wild rodents such as the herbivorous cotton rat (Sigmodon hispidus) reside on many of these toxic waste sites, we explored the sensitivity of their immune systems to oral exposures of environmentally relevant concentrations of inorganic arsenic. We exposed adult male cotton rats (n = 36) to either 0 (controls), 5 (low dose), or 10 (high dose) ppm sodium arsenite in drinking water for 6 weeks. Daily food intake decreased in a dose-dependent manner, ranging from an average of 10.03 ± 0.45 in the high-dose group to 11.27 ± 0.42 (SE) g/animal/day in the control group. Mass of testes in the low-dose group increased significantly compared to controls, but there was no difference between the high-dose and control groups. Masses of liver, kidney, adrenals, popliteal lymph nodes, spleen, epididymides, and seminal vesicles and selected hematological parameters were unaffected by arsenic exposure. In vivo cell-mediated immunity, as measured by a phytohemagglutinin-hypersensitivity response to an intradermal challenge, was suppressed 30% in the low-dose group compared to controls; however, responses of those receiving a high dose of arsenic were similar to controls. Arsenic treatment did not have a measurable impact on lymphoproliferative responses of cultured splenocytes to the mitogens Concanavalin A and Pokeweed mitogen, or to the lymphokine interleukin-2. We also observed no impact of low-level arsenic exposure on macrophage phagocytic activity and tumoricidal activity of lymphokine-activated killer cells in vitro. It is possible that malnutrition caused by decreased food intake may eventually lead to atrophy of lymphoid organs and render animals more susceptible to environmental pathogens. However, direct effects of low-level arsenic exposure on immune function of cotton rats was minimal (a moderate depression in the in vivo cell-mediated immunity assay) and may not be clinically relevant with regard to susceptibility to disease in the wild.
35 citations
TL;DR: The results suggest that elevated levels of heme oxygenase alone are not responsible for arsenite-mediated decreases in CYP2H, suggesting that the decreases in this form of CYP occurred post-transcriptionally.
TL;DR: It is hypothesised that incorporation of selenol metabolites of Selenite into the glutathione complexes of arsenic and antimony, resulting in cholephilic ternary complexes, accounts for the arsenic- and antium-induced augmentation of the hepatobiliary transport of seenium.
TL;DR: The results suggested that the major and minor organic arsenic compounds contained in marine fishery products are much less cytotoxic inorganic arsenic, methylarsonic acid and dimethylarsinic acid.
Abstract: Arsenobetaine, arsenocholine, trimethylarsine oxide and tetramethylarsonium iodide, which are contained in marine fishery products, were examined for their potencies on cell growth inhibition, chromosomal aberration and sister chromatid exchange (SCE). Arsenobetaine, the major water-soluble organic arsenic compound in marine animals, exhibited very low cytotoxicity towards mammalian cells. This compound showed no cell growth inhibition at a concentration of 10 mg cm -3 and the cytotoxicity was lower than 1/14 000th of that of sodium arsenite and 1/1600th of that of sodium arsenate towards BALB/c 3T3 cells. The chromosomal aberrations caused by arsenobetaine at a concentration of 10 mg cm -3 consisted mainly of chromatid gaps and chromatid breaks, but in this concentration chromosomal breakage owing to its osmotic pressure is likely to be considerable. No SCE was observed at a concentration of 1 mg cm -3 . Arsenocholine and trimethylarsine oxide also showed no cell growth inhibited at a concentration of 10 mg cm -3 . However, tetramethylarsonium iodide inhibition the growth of BALBIc 3T3 at a concentration of 8 mg cm -3 . These compounds exhibited a low ability to induce chromosomal aberrations at a concentration range of 2-10 mg cm -3 and no SCE was observed at a concentration of 1.0 mg cm -3 . These results suggested that the major and minor organic arsenic compounds contained in marine fishery products are much less cytotoxic inorganic arsenic, methylarsonic acid and dimethylarsinic acid.
TL;DR: Exposure to arsenite may be a simple way of assessing whether Ras plays an essential role in mediating activation of the MAP kinase cascade by extracellular signals.
Abstract: Pretreatment of cells with 0.5 mM sodium arsenite (but not other activators of stress-activated MAP kinase cascades) prevents the activation of p21Ras and strongly suppresses the activation of c-Raf and the MAP kinase cascade by a variety of growth factors. Arsenite appears to exert its effect by preventing the guanine nucleotide exchange factor mSos from converting Ras to its active GTP-bound state. Exposure to arsenite may be a simple way of assessing whether Ras plays an essential role in mediating activation of the MAP kinase cascade by extracellular signals.
TL;DR: The effects of different levels of arsenic (As) and salinity on bean plant (Phaseolus vulgaris L., cv. Buenos Aires) nutrition were investigated in this article, where the processes of absorption and accumulation of chloride (Cl) and micronutrient elements: boron (B), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn).
Abstract: The effects of different levels of arsenic (As) and salinity on bean plant (Phaseolus vulgaris L., cv. Buenos Aires) nutrition were investigated. We studied the processes of absorption and accumulation of chloride (Cl) and micronutrient elements: boron (B), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn). The experiment was performed in soilless culture at two levels of As: 2 and 5 mg As L‐1 [added as sodium arsenite (NaAsO2)], and three saline levels [only sodium chloride (NaCl) was added]: 1, 2, and 4 dSm‐1. Sodium arsenite and NaCl significantly affected micronutrients allocation within the bean plant at levels used in this study. Arsenite depressed Mn and Cl concentrations in the root, whereas root B, Cu, and Zn levels were increased. Boron, Cu, Fe, and Cl concentrations were significantly higher in As‐stressed plants compared with controls. The addition of NaCl increased the Cl and Mn concentrations in roots and Cl, Fe, and Mn in leaves.
TL;DR: It is indicated that preinduction of a heat-shock response (arsenite) can protect against cytokine or LPS-induced apoptosis and enterocyte dysfunction, as manifested by the passage of E. coli across an intact enterocyte monolayer.
Abstract: OBJECTIVES a) To determine if the sequence of exposure of intestinal epithelial cells to heat-shock or acute-phase stimuli would affect whether cellular protection or injury would occur; and b) to determine if the effects of a thermally induced heat-shock response can be mimicked by sodium arsenite, a nonthermal inducer of the heat-shock response. DESIGN In vitro controlled study. SETTING Institutional laboratories. SUBJECTS Caco-2 human intestinal cell line. INTERVENTIONS Human intestinal epithelial cells (Caco-2) were grown on 35-mm culture dishes, chamber slides, or in a bicameral culture system to confluence or until tight-junction integrity was established. The cells were examined for viability, apoptosis, and bacterial translocation after exposure to a series of insults. MEASUREMENTS AND MAIN RESULTS Control Caco-2 cells (medium only) and cells exposed to arsenite or to LPS alone had an apoptotic cell rate of 5.7%, 7.9%, and 8.6%, respectively. However, Caco-2 cells exposed to the cytokines IL-1beta and IL-6 had a significantly higher rate of apoptosis (22.1%, p < .01 vs. other groups). Caco-2 cells exposed to arsenite followed by LPS had 6.7% apoptotic cells, while cells exposed to LPS followed by arsenite had a significantly greater number of apoptotic cells (19.7%, p < .05). In addition, cells exposed to cytokines followed by arsenite had a higher apoptotic rate than cells exposed to arsenite followed by cytokines (28.4% vs. 10.6%, p < .01). Similar results were seen when cell viability was quantitated. At 3 hrs after challenge with Escherichia coli, the cytokine-exposed Caco-2 monolayers had a significantly increased rate of bacterial passage across the Caco-2 monolayer than control monolayers (p < .05), while the Caco-2 monolayers exposed to arsenite followed by cytokines or arsenite alone had a decreased rate of bacterial passage (p < .05). Conversely, cells exposed to cytokines or LPS before arsenite had the highest number of bacteria crossing the monolayer (p < .05). CONCLUSIONS These results indicate that preinduction of a heat-shock response (arsenite) can protect against cytokine or LPS-induced apoptosis and enterocyte dysfunction, as manifested by the passage of E. coli across an intact enterocyte monolayer. In contrast, the induction of a heat-shock response after exposure to acute-phase response inducers (cytokines and LPS) may result in decreased enterocyte viability, increased apoptosis, and cellular dysfunction.
TL;DR: In this paper, the effects of arsenic contamination on the processes of uptake and accumulation of macronutrient elements calcium (Ca), potassium (K), magnesium (Mg), nitrogen (N), and phosphorus (P) in tomato plants were studied.
Abstract: As a part of a general study of environmental contamination by arsenic (As), the effects caused by arsenite on the processes of uptake and accumulation of macronutrient elements calcium (Ca), potassium (K), magnesium (Mg), nitrogen (N), and phosphorus (P) in tomato plants (Lycopersicum esculentum Mill, cultivar Marmande) were studied. Tomato plants were grown in nutrient solution (hydroponic growing system) containing three levels of As (added as sodium arsenite, NaAsO2): 2, 5, and 10 mg As L‐1. One control, with no As addition, was also included. Vegetative growth and fruit yield were affected by As level in the nutrient solution. Plant growth, expressed as dry and fresh weights of leaves and roots, were significantly restricted by As. Fresh fruit production decreased to 60.7, 47.3, and 23.3% at 2, 5, and 10 mg As L‐1, respectively, compared to control. Contamination by As caused changes in both concentration and uptake of all the macronutrients studied. A reduction in the root concentration of ...
TL;DR: Gallium arsenide administration does significantly induces MT in hepatic tissues accompanied by an increase in cytosolic glutathione, arsenic, zinc and copper concentration, which proves that arsenic moiety is chiefly responsible for such an effect.
Abstract: Metallothionein genes (MT) are inducible by a variety of agents, including heavy metals. We report the induction of MT expression by gallium arsenide (GaAs), a superior intermetallic semiconductor material at two time intervals following single oral exposure in rats. The data is also supplemented with two additional groups exposed to gallium (III) as gallium oxide and arsenic (III) as sodium arsenite to determine which of the two moieties in GaAs is responsible for any such possible effects. The results indicate that GaAs administration does significantly induces MT in hepatic tissues accompanied by an increase in cytosolic glutathione, arsenic, zinc and copper concentration. It thus proves that arsenic moiety is chiefly responsible for such an effect.
Journal Article•
Journal Article•
TL;DR: In this article, chronic arsenic toxicity was induced in goats by oral administration of sodium arsenite @25.0mg/kg b. wt. daily for 12 weeks and the elimination of arsenic mainly occured through the faeces and skin.
Abstract: Chronic arsenic toxicity was induced in goats by oral administration of sodium arsenite @25.0mg/kg b. wt. daily for 12 weeks. Clinically ,there were dcvelopment of gastrointestinaL and nephritic signs with 100% mortality. Intoxicated goats had Leucopaenia, anaemia and increased erythrocyte fragility rate. Rumen pH became acidic with complete absence of its protozoan activity. An increased BSP clearance time was observed in the intoxicated goats. Urinanalysis revealed low specific gravity and pH alongwith marked presence of protein, sugar, cast, pus cells and arsenic (>70% mg%). Significantly decreased concentrations of urea nitrogen and creatinine with increase of alkaline phosphates were observed in urine. The elimination of arsenic mainly occured through the faeces and skin.
TL;DR: The alkylating activity of cytosol prepared from the common earthworm, Lumbricus terrestris, towards sodium arsenite has been investigated and suggests that earthworm cytOSol has the same methylating reactivity towards arsenite as do similar preparations from various tissues of several species of mammals.