Toxicity Of Inorganic Arsenic Research Articles

Influence of humic acid and fluvic acid on the altered toxicities of arsenite and arsenate toward two freshwater algae.

Arsenic pollution in freshwater poses a serious threat to aquatic organisms. However, dissolved organic matter (DOM) in water can modulate arsenic environmental toxicity by either suppressing or promoting its bioaccumulation. In this study, we investigated the toxicity, bioaccumulation, and biotransformation of inorganic arsenic (arsenite AsIII and arsenate AsV) combined with two types of DOM, i.e., humic acid (HA) and fulvic acid (FA), in the algae Chlamydomonas reinhardtii and Ochromonas danica. C. reinhardtii has a cell wall and cannot bioaccumulate arsenic complexation, whereas O. danica has no cell wall. Without DOM, AsV was more toxic than AsIII for C. reinhardtii, and AsV was less toxic than AsIII for O. danica. HA and FA addition reduced AsV and AsIII toxicities; the larger molecular weight (Mw) of HA contributed to the reduction in toxicity to an even greater extent, and reduced arsenic accumulation while promoting the biotransformation ability of C. reinhardtii, which has a cell wall. However, HA and FA addition increased AsV and AsIII toxicities and arsenic accumulation while relatively enhancing the biotransformation ability of O. danica, which has no cell wall. Coupling toxicity, bioaccumulation, and biotransformation, DOM (HA and FA) contributed to the altered toxicity of freshwater algae to AsV and AsIII through reduced/increased arsenic accumulation and enhanced biotransformation. Overall, our study considered the combined toxicity of inorganic arsenic and DOM in phytoplankton, helping estimate the potential environmental risk of arsenic in aqueous environments.

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Curcumin sensitizes Epstein-Barr-immortalized lymphoblastoid cell lines to inorganic arsenic toxicity.

Chronic exposure to inorganic arsenic (iAs) through contaminated drinking water is an important health problem in certain countries. The use of phytochemicals such as curcumin has recently emerged as an alternative strategy for preventing cellular damage caused by iAs. The Epstein-Barr virus (EBV) affects ~90% of the population and experimental evidence suggested that curcumin mediates cytotoxicity against EBV-infected cells. Due to the potential for an interaction of these factors, the aim of the present study was to evaluate the effect of this phytochemical on iAs-related toxicity in EBV-infected cells. Two independent EBV-immortalized human lymphoblastoid cell lines (LCLs) were used as the model. The cell lines were first incubated with increasing concentrations of curcumin or iAs for 24 and 15 h, respectively, to determine the individual effects of each exposure on cell death. In the next experiment, cell cultures were pre-incubated with 5 µM curcumin for 9 h prior to treatment with 10 µM iAs for 15 h, followed by evaluation of cell death and the cell cycle profile via flow cytometry. The results indicated that individual treatment with either curcumin or iAs induced cell death in a concentration-dependent manner. Furthermore, curcumin pre-treatment enhanced iAs-induced cell death and promoted cell cycle arrest in G1 phase. Taken together, these results suggested that curcumin sensitizes EBV-positive LCLs to the cytotoxic effects of iAs.

Associations between blood arsenic and urinary arsenic species concentrations as an exposure characterization tool

Blood arsenic has various toxicities including carcinogenicity, but urinary concentrations are often substituted to determine the exposure level. Since there is little information on the relation of urinary arsenic species to blood arsenic, the aim was to investigate relationships between blood total arsenic (T-As) and the urinary species adjusted by creatinine and specific gravity (SG). Blood and spot urine samples were collected from 109 Japanese subjects aged 18–66 years without occupational exposure. Positive correlations of blood T-As (median, 3.49 μg/L) with urinary creatinine-adjusted and SG-adjusted T-As and arsenobetaine were statistically significant and greater than those with the unadjusted ones. The magnitude of associations of blood T-As with creatinine-adjusted arsenic species was significantly larger than those with unadjusted or SG-adjusted ones. Most of the correlation coefficients among urinary arsenic species concentrations were significant in three adjustment methods, but there was not a significant correlation between monomethylarsonic acid and arsenobetaine after urinary creatinine and SG corrections. Given multiple regression analysis, plasma T-As concentrations showed significant relations to creatinine-adjusted T-As, dimethylarsinic acid, and arsenobetaine concentrations, but erythrocyte T-As did hardly reflect the variation of urinary arsenic species. In conclusion, creatinine-adjusted arsenic concentrations are suggested to be the most appropriate predictor of blood T-As; by contrast, use of the urinary unadjusted arsenic concentration may result in a misleading interpretation of inorganic arsenic toxicity because the associations between inorganic and organic arsenic species based on the unadjusted concentration were mutually close. Plasma T-As appeared to be the best indicator of low-level exposure in blood samples.

Modulation of glutathione S-transferase and superoxide dismutase in response to heavy metals in brackish water flea Diaphanosoma celebensis

Superoxide dismutase (SOD) and glutathione S-transferase (GST) serve as biomarkers of oxidative stress in aquatic organisms. However, the modulatory effects of heavy metals on the expression of small crustaceans are yet unknown. The acute toxicity of inorganic arsenic (As), cadmium (Cd), and lead (Pb) to the brackish water flea Diaphanosoma celebensis (4 days old) was evaluated to determine their sublethal concentrations. Modulations in the activities and transcription of SODs (Cu/Zn-SOD and Mn-SOD) and GSTs (mu, kappa, theta, and sigma) in response to sublethal concentrations of heavy metals were investigated for 48 h. The 48-h median lethal concentration (LC50) was determined to be 2.62 mg/L, 2.60 mg/L, and 0.37 mg/L for Cd, As, and Pb, respectively, and the order of toxicity in this species was Pb > Cd = As. SOD and GST activities were induced after exposure to all metals; in particular, GST activity was sensitively enhanced upon As exposure. Real-time reverse-transcriptase polymerase chain reaction showed that GST mu and GST sigma were specific for As, and GST kappa and GST theta for Cd. Mn-SOD mRNA expression was more sensitive to As. These findings suggest that D. celebensis SOD and GST may be involved in the antioxidant defense mechanisms to heavy metals. These genes may serve as useful biomarkers for risk assessment of heavy metal pollution in aquatic ecosystems. This study may be helpful for the better understanding of the molecular mode of action of heavy metals in small crustaceans and provide preliminary data for future studies evaluating the combined effects of heavy metal mixture.

In Vitro Evaluation of the Protective Role of Lactobacillus StrainsAgainst Inorganic Arsenic Toxicity.

Inorganic arsenic [iAs, As(III)+ As(V)] is considered a human carcinogen. Recent studies show that it has also toxic effects on the intestinal epithelium which might partly explain its systemic toxicity. The aim of this study is to evaluate the protective role of lactic acid bacteria (LAB) against the toxic effects of iAs on the intestinal epithelium. For this purpose, the human colonic cells Caco-2 were exposed to As(III) in the presence of various LAB strains or their conditioned medium. Results showed that some strains and their conditioned media partially revert the oxidative stress, the production of pro-inflammatory cytokines, the alterations of the distribution of tight junction proteins, and the cell permeability increases caused by As(III). These results show that both soluble factors secreted or resulting from LAB metabolism and cell-cell interactions are possibly involved in the beneficial effects. Therefore, some LAB strains have potential as protective agents against iAs intestinal barrier disruption.

Selenium intake from tuna in Galicia (Spain): Health risk assessment and protective role against exposure to mercury and inorganic arsenic

This study aims to quantify the selenium contribution from tuna to the Spanish diet and evidence the Se protective role against mercury and inorganic arsenic toxicity. Selenium concentrations in tuna were determined by ICP-MS spectrometry (expressed as mg kg−1), and the risk assessment was evaluated joined to Hg and iAs contrasting criteria of regulatory agencies with those that consider the Se protective role. Differences between Se average concentrations in fresh (1.24) and preserved (1.17) tuna were not statistically significant. In canned tuna species, Se presented higher mean levels in Thunnus albacares (1.28) than Thunnus alalunga (1.01) with statistically significant differences (p = 0.002), and among canned preparations a decreasing sequence was observed in different preparation-packaging media: oil (1.42) > natural (1.01) > pickled (0.92). Statistical study showed Hg-iAs as the only pair significantly correlated in all samples. The HI (sum of individual target hazard quotients –THQs-) on the consumption of tuna in Spain, due to exposure to Se, Hg and iAs, revealed the possibility of risk of adverse chronic effects in the six-year-old children group (1.09). According to the maximum allowable tuna consumption rate in meals/week (CRmw) and the THQs obtained, tuna intake, especially in children, should be moderated. The health benefit values (HBVSe) were positive in all samples, 14.53 and 15.65 in fresh and preserved tuna, respectively, which allows tuna to be considered safe. The benefit-risk value (BRV) evidenced the Se molar excess with respect to Hg that reached a surplus of 14.32% on Se AI in adults. Since iAs reduces the Se bioavailability, applying a new BRV criterion, the aforementioned percentage decreased to 13.49% of Se AI. In conclusion, tuna offers high levels of selenium to counteract adverse effects by the presence of Hg and iAs, and to provide consumers an important source of this essential element safely.

Bioaccumulation and biotransformation of arsenic by the brown macroalga Sargassum patens C. Agardh in seawater: effects of phosphate and iron ions

The toxicity and bioaccumulation and biotransformation potential of inorganic arsenic (IAs) species As(V) and As(III) were investigated using Sargassum patens under laboratory culture for 7 days. Algal chlorophyll fluorescence decreased with increasing As(V) and As(III) concentrations, being significantly affected by As(III) treatments. Higher As(III) concentration negatively affected growth rate, and P and Fe limitation greatly enhanced IAs toxicity. The extracellular, intracellular, and total bioaccumulation of As(III) and As(V) varied significantly depending on initial concentrations and addition of P and Fe. P and Fe availability suppressed intracellular As accumulation in As(V) medium but not in As(III) medium. In P-rich (10 μmol L−1) medium, intracellular As was reduced by 4.7% and 9.9% when As(V) in the medium was constant (4.0 μmol L−1), under Fe-limited (0 μmol L−1) and Fe-rich (10 μmol L−1) conditions, respectively. However, the Fe-rich condition positively affected extracellular As accumulation from both As source. Extracellular As increased by 43.5% and 38.8% in P-limited + Fe-rich cultures with 4.0 μmol L−1 of As(V) and As(III), respectively. Algae exhibited greater absorption and adsorption to As(V) than to As(III). The reduced metabolites of As(III) (3.5 to 4.9% of the total As) and oxidized metabolites of As(V) (2.0 to 3.7% of the total As) were recorded as biotransformed species from coexisting media containing As(V) and As(III) at a constant 4.0 μmol L−1, respectively. Both P and Fe had significant influences on the variation in behaviors of IAs. This information is vital in terms of As research in marine ecosystems.

Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and epididymal histophysiology in rats.

For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2 (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity.

Review of arsenic speciation, toxicity and metabolism in microalgae

Arsenic is a toxic metalloid and its pollution has become a global environmental problem. This paper reviewed the current knowledge on the speciation, toxicity and metabolism of arsenic in microalgae. A number of arsenic species are present in various microalgae. Due to the great toxicity of inorganic arsenic, microalgae may undergo different processes to reduce the arsenic toxicity, including cell surface binding, arsenite [As(III)] oxidation, arsenate [As(V)] reduction, methylation, transformation into arsenosugars or arsenolipids, chelation of As(III) with glutathione and phytochelatins, as well as excretion from cells. Several genes and enzymes involved in arsenic transformations have been identified and characterized. Many factors, especially nutrient elements (e.g., nitrogen and phosphorus) in cells and in culture, affect arsenic metabolic pathways of microalgae. Arsenic metabolism in the unicellular algae has gained considerable interest because these processes control not only the effectiveness of arsenic phycoremediation, but also the risk of arsenic contamination in algal products. Future research need to focus on (1) the regulative mechanisms of arsenic absorption, biotransformation and excretion at molecular level; (2) the effects of intracellular nutrient dynamics on arsenic speciation; (3) the impacts of culture regime on the arsenic metabolism in microalgae; (4) the transfer of arsenic species across aquatic food web in order to better evaluate the roles of microalgae in arsenic cycling.

Response of growth and superoxide dismutase to enhanced arsenic in two Bacillus species.

Species differences in inorganic arsenic tolerance were investigated by comparing the responses of Bacillus subtilis (B. subtilis) and Bacillus thuringiensis (B. thuringiensis) to elevated concentrations of As(III) and As(V). The cell densities in treatments were always lower during the experiment compared to controls, with the exception of exposure to 1.0 mg As(V) l(-1) on the first day. It was also found that relative growth rate (RGR) of B. thuringiensis was lower than that of B. subtilis. Furthermore, RGR of each Bacillus species was negative correlation with toxicity of inorganic arsenic. However, total cell number still increased in each treatment according to cell density and RGR assays. Superoxide dismutase (SOD) activity of both Bacillus species was promoted by As(III) and As(V), especially under high arsenic concentration condition. In addition, SOD activity of B. thuringiensis was higher than that of B. subtilis during the same exposure time. In lipid peroxidation assay, thiobarbituric acid-reactive substances (TBARS) content of each Bacillus species had a significant increase with increment of arsenic concentration. Moreover, significant difference was observed between the two Bacillus species under high arsenic concentration. TBARS content of B. thuringiensis was higher than that of B. subtilis, indicating that effect of arsenic on cell membranes of B. thuringiensis was much more than that of B. subtilis. These results suggest that the two Bacillus species could adapt and live in high arsenic aquifers, although their growth and cell membranes were affected by As treatment in a way.

Mode of action for inorganic arsenic toxicity and carcinogenesis

Inorganic arsenic (iAs) at high doses is a known human carcinogen, inducing tumors of the skin, urinary bladder, and lung. It is also associated with non-cancer toxicities. An understanding of the mode of action (MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models, and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity (>0.1 μmol/L trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm (1 ppm = 1 mg/L) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, non-cancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs.

Speciation without Chromatography Using Selective Hydride Generation: Inorganic Arsenic in Rice and Samples of Marine Origin

Because of the toxicity of inorganic arsenic (iAs), only iAs needs to be monitored in food and feedstuff. This demands the development of easy and quick analytical methods to screen large number of samples. This work focuses on hydride generation (HG) coupled with an ICPMS as an arsenic detector where the HG is added as a selective step to determine iAs in the gaseous phase while organically bound As remains in the solution. iAs forms volatile arsine species with high efficiency when treated with NaBH4 at acidic conditions, whereas most other organoarsenic compounds do not form any or only less volatile arsines. Additionally, using high concentrations of HCl further reduces the production of the less volatile arsines and iAs is almost exclusively formed, therefore enabling to measure iAs without a prior step of species separation using chromatography. Here, we coupled a commercially available HG system to an ICPMS and optimized for determination of iAs in rice and samples of marine origin using different acid concentrations, wet and dry plasma conditions, and different reaction gas modes. Comparing this method to conventional HPLC-ICPMS, no statistical difference in iAs concentration was found and comparable limits of detections were achieved using less than half the instrument time.

Total and inorganic arsenic in dietary supplement supplies in northern Mexico

The aim of this study was to evaluate the presence of total and inorganic arsenic in dietary supplements composed of herbal plants and seaweed, and to determine the potential toxicological risk. Total arsenic was determined by dry ashing and hydride generation atomic absorption spectrometry, and inorganic arsenic was determined by acid digestion, solvent extraction, and hydride generation atomic absorption spectrometry. Total and inorganic arsenic in the supplements ranged from 0.07 to 8.31mg kg(-1) dry weight and from 0.14 to 0.28mg kg(-1) dry weight, respectively. Daily intake of total arsenic ranged from 0.05 to 12.46μg day(-1). Inorganic arsenic intake ranged from 0.21 to 0.83μg day(-1), values that are below the Benchmark Dose Lower Confidence Limit recommended by the Word Health Organization. Therefore, there appears to be a low risk of adverse effects resulting from excess inorganic arsenic intake from these supplements. This is the first study conducted in Mexico that investigates total and inorganic arsenic in dietary supplements. Although the results do not suggest toxicological risk, it is nonetheless important considering the toxicity of inorganic arsenic and the increasing number consumer preferences for dietary supplements. Moreover, it is important to improve and ensure the safety of dietary supplements containing inorganic arsenic.

Diet's role in the toxicity of inorganic arsenic (iAs): A journey from soil to children's mouth

Arsenic is widely distributed in the environment, particularly in soil. Absorption of arsenic and other metalloids from soil can alter the nutritional composition of some foods such as rice and vegetables. Rice has been found to contain a high amount of inorganic arsenic (iAs) that the plant accumulates from soil. A diet enriched of rice and rice based foods, such as in the case of children affected by celiac disease, can be therefore a toxicological issue. Vegetables are rich in antioxidants and folic acid that contribute to minimize some arsenic-induced toxic effects. Therefore, diet appears as a crucial determinant in the axis soil–food–human health. We preliminarily investigated the As exposure effects in in vitro models and we identified the principal interactors (mainly genes) involved in As-induced toxicity linked to specific metabolic pathways. We suggested that As-exposure and toxicity are more generally linked to diet and that diet can have a role in modulating and mitigating these toxic effects. In conclusion, we suggested that a more integrated view of ‘exposure’ to toxic elements should also include other factors, such as the diet contribution, other than environmental and toxicological data.

Arsenic-Induced Straighthead: An Impending Threat to Sustainable Rice Production in South and South-East Asia!

Straighthead is a physiological disorder of rice (Oryza sativa L.) that results in sterile florets with distorted lemma and palea, and the panicles or heads may not form at all in extreme cases. Heads remain upright at maturity, hence the name 'straighthead'. The diseased panicles may not emerge from the flag leaf sheath when the disease is severe. Straighthead disease in rice results in poorly developed panicles and significant yield loss. Although other soil physicochemical factors involved, arsenic contamination in soil has also been reported to be closely associated with straighthead of rice. Monosodium methanearsonate has been a popular herbicide in cotton production in the USA, which has shown to cause injuries in rice that are similar to straighthead. Since toxicity of inorganic arsenic (iAs) is higher than other forms of arsenic, it may produce a more severe straighthead disorder in rice. The use of iAs-rich groundwater for irrigation, and the increase of iAs concentrations in agricultural soil in arsenic epidemic South and South-East Asia may cause a high incidence of straighthead in rice, resulting in a threat to sustainable rice production in this region.

Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms

Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.