Arsenic Toxicity Research Articles

Synergistic role of melatonin and hydrogen sulfide in modulating secondary metabolites and metal uptake/sequestration in arsenic-stressed tomato plants

The multifunctional roles of melatonin (ML) and hydrogen sulfide (H2S) as plant gasotransmitters are well understood. However, their interaction in defensive responses is still unclear. Here, we assessed how the ML-H2S interaction impacts tomato plants exposed to arsenic (As, 10 mg/L) toxicity. The results showed that ML and ML+H2S treatments alleviated As toxicity by inducing the transcription of ANS, PAL, DFR, CHS, F3H, and CHI and an enhanced accumulation of phenolic and anthocyanin compounds. ML and ML+H2S led to a drop in the transcription of PT2 and Lsi1, resulting in reduced As uptake and subsequent movement to the leaves. ML and ML+H2S treatments resulted in high GSH1, PCS, and ABC1 transcription. This led to elevated levels of glutathione and phytochelatins, facilitating As sequestration in the roots and protecting root and leaf cells against As. ML and ML+H2S treatments enhanced tomato growth under As treatments by optimizing chlorophyll metabolism, increasing internal H2S, and amplifying the antioxidant machinery function. In contrast to the sole use of ML treatment, ML+H2S exhibited more pronounced positive impacts on As-stressed tomatoes, indicating synergistic/interactive effects between these two substances. On the other hand, the use of hypotaurine, an H2S scavenger, demonstrated the inhibition of the beneficial impact of ML and ML+H2S treatments in stimulating defensive responses, which highlights the substantial involvement of H2S in the signaling pathway activated by ML during As stress. Hence, we can conclude that ML requires the presence of endogenous H2S to mitigate the adverse effects of As on tomato seedlings.

Significance of dietary quinoa husk (Chenopodium quinoa) in gene regulation for stress mitigation in fish

The persistent challenges posed by pollution and climate change are significant factors disrupting ecosystems, particularly aquatic environments. Numerous contaminants found in aquatic systems, such as ammonia and metal toxicity, play a crucial role in adversely affecting aquaculture production. Against this backdrop, fish feed was developed using quinoa husk (the byproduct of quinoa) as a substitute for fish meal. Six isonitrogenous diets (30%) and isocaloric diets were formulated by replacing fish meal with quinoa husk at varying percentages: 0% quinoa (control), 15, 20, 25, 30 and 35%. An experiment was conducted to explore the potential of quinoa husk in replacing fish meal and assess its ability to mitigate ammonia and arsenic toxicity as well as high-temperature stress in Pangasianodon hypophthalmus. The formulated feed was also examined for gene regulation related to antioxidative status, immunity, stress proteins, growth regulation, and stress markers. The gene regulation of sod, cat, and gpx in the liver was notably upregulated under concurrent exposure to ammonia, arsenic, and high-temperature (NH3 + As + T) stress. However, quinoa husk at 25% downregulated sod, cat, and gpx expression compared to the control group. Furthermore, genes associated with stress proteins HSP70 and DNA damage-inducible protein (DDIP) were significantly upregulated in response to stressors (NH3 + As + T), but quinoa husk at 25% considerably downregulated HSP70 and DDIP to mitigate the impact of stressors. Growth-responsive genes such as myostatin (MYST) and somatostatin (SMT) were remarkably downregulated, whereas growth hormone receptor (GHR1 and GHRβ), insulin-like growth factors (IGF1X, IGF2X), and growth hormone gene were significantly upregulated with quinoa husk at 25%. The gene expression of apoptosis (Caspase 3a and Caspase 3b) and nitric oxide synthase (iNOS) were also noticeably downregulated with quinoa husk (25%) reared under stressful conditions. Immune-related gene expression, including immunoglobulin (Ig), toll-like receptor (TLR), tumor necrosis factor (TNFα), and interleukin (IL), strengthened fish immunity with quinoa husk feed. The results revealed that replacing 25% of fish meal with quinoa husk could improve the gene regulation of P. hypophthalmus involved in mitigating ammonia, arsenic, and high-temperature stress in fish.

Arsenic Species Distribution and Toxicity in the Environment, Bioaccumulation, Biomethylation and Bioremediation by Microalgae: A Review

Arsenic (As) is a noxious metalloid that has been designated a priority pollutant and is present in the environment as a consequence of both anthropogenic and natural processes. Its toxicity in environmental and biological systems depends strongly on the chemical species. Interest in arsenic and microalgae interactions is important because microalgae are at the base of the aquatic food chain, are used in animal nutrition and has potential for As phytoremediation. This paper reviewed the current information on As species distribution in the environment especially as it relates to its toxicity to microalgae as well as its bioaccumulation, biomethylation and bioremediation by microalgae using appropriate methods. Information obtained revealed that Microalgae have evolved mechanisms for dealing with As in the environment with arsBHC operon mediating the reduction and extrusion of arsenite from the cells. They accumulate large amounts of arsenic from their surroundings which could lead to toxicity, As excretion from cells, reduction, methylation or complexation with metal binding peptides like glutathione and phytochelatins. This has made them suitable as ecological indicators to give an indication of As bioavailability and also in possible applications for the process of As remediation. Microalgae are been proposed for bioremediation purposes in aquatic environment since they show a high capacity for biosorption and bioconcentration of As and most importantly since they are able to methylate inorganic As to non-toxic organic and volatile As.

Diagnosing arsenic-mediated biochemical responses in rice cultivars using Raman spectroscopy.

Rice (Oryza sativa) is the primary crop for nearly half of the world's population. Groundwater in many rice-growing parts of the world often has elevated levels of arsenite and arsenate. At the same time, rice can accumulate up to 20 times more arsenic compared to other staple crops. This places an enormous amount of people at risk of chronic arsenic poisoning. In this study, we investigated whether Raman spectroscopy (RS) could be used to diagnose arsenic toxicity in rice based on biochemical changes that were induced by arsenic accumulation. We modeled arsenite and arsenate stresses in four different rice cultivars grown in hydroponics over a nine-day window. Our results demonstrate that Raman spectra acquired from rice leaves, coupled with partial least squares-discriminant analysis, enabled accurate detection and identification of arsenic stress with approximately 89% accuracy. We also performed high-performance liquid chromatography (HPLC)-analysis of rice leaves to identify the key molecular analytes sensed by RS in confirming arsenic poisoning. We found that RS primarily detected a decrease in the concentration of lutein and an increase in the concentration of vanillic and ferulic acids due to the accumulation of arsenite and arsenate in rice. This showed that these molecules are detectable indicators of biochemical response to arsenic accumulation. Finally, a cross-correlation of RS with HPLC and ICP-MS demonstrated RS's potential for a label-free, non-invasive, and non-destructive quantification of arsenic accumulation in rice.

Root-exuded specialized metabolites reduce arsenic toxicity in maize

By releasing specialized metabolites, plants modify their environment. Whether and how specialized metabolites protect plants against toxic levels of trace elements is not well understood. We evaluated whether benzoxazinoids, which are released into the soil by major cereals, can confer protection against arsenic toxicity. Benzoxazinoid-producing maize plants performed better in arsenic-contaminated soils than benzoxazinoid-deficient mutants in the greenhouse and the field. Adding benzoxazinoids to the soil restored the protective effect, and the effect persisted to the next crop generation via positive plant-soil feedback. Arsenate levels in the soil and total arsenic levels in the roots were lower in the presence of benzoxazinoids. Thus, the protective effect of benzoxazinoids is likely soil-mediated and includes changes in soil arsenic speciation and root accumulation. We conclude that exuded specialized metabolites can enhance protection against toxic trace elements via soil-mediated processes and may thereby stabilize crop productivity in polluted agroecosystems.

Mechanistic insight into the intensification of arsenic toxicity to rice (Oryza sativa L.) by nanoplastic: Phytohormone and glutathione metabolism modulation

In this study, nanoplastic (NPs) at environmentally relevant concentration (0.001% w/w) had no effect on the growth of rice, while significantly elevated the phytotoxicity of As (III) by 9.4–22.8% based on the endpoints of biomass and photosynthesis. Mechanistically, NPs at 0.001% w/w enhanced As accumulation in the rice shoots and roots by 70.9% and 24.5%, respectively. Reasons of this finding can was that (1) the co-exposure with As and NPs significantly decreased abscisic acid content by 16.0% in rice, with subsequent increasing the expression of aquaporin related genes by 2.1- to 2.7-folds as compared with As alone treatment; (2) the presence of NPs significantly inhibited iron plaque formation on rice root surface by 22.5%. We firstly demonstrated that “Trojan horse effect” had no contribution to the enhancement of As accumulation by NPs exposure. Additionally, NPs disrupted the salicylic acid, jasmonic acid, and glutathione metabolism, which subsequently enhancing the oxidation (7.0%) and translocation (37.0%) of in planta As, and reducing arsenic detoxification pathways (e.g., antioxidative system (28.6–37.1%), As vacuolar sequestration (36.1%), and As efflux (18.7%)). Our findings reveal that the combined toxicity of NPs and traditional contaminations should be considered for realistic evaluations of NPs.

Toxic Effects of Arsenic on Four Freshwater Aquatic Species and Its Transformation Metabolism in Crucian Carp (Carassius auratus).

Inorganic arsenic is a well-known carcinogen that is much more toxic than its organic counterpart. While much is known about the accumulation and transformation of arsenic in marine organisms, little is known regarding these processes in freshwater aquatic species. In this study, the acute toxicity and toxicological effects of inorganic arsenic on four freshwater organisms (Cyprinus carpio, Misgurnus anguillicaudatus, Pseudorasbora parva, Eriocheir sinensis) commonly found in rice-fish farming systems were investigated. The organisms exhibited different levels of sensitivity to inorganic arsenic, with crustaceans being more sensitive than fish. Fish were found to be more tolerant to As(V) than As(III). The study also investigated the accumulation, transformation, and release of inorganic arsenic in crucian carp, an omnivorous species with high environmental tolerance. The fish accumulated As(III) rapidly in various tissues, and were able to transport it to other tissues through gills, intestines, and skin. The accumulated As(III) was converted into less toxic forms, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), via methylation. The fish also converted As(III) into arsenate (AsV) via enzymatic and oxidative reactions. After the transferal to clean water, the forms of arsenic in the various tissues decreased rapidly, but the rates of excretion of the four forms of arsenic were not the same among the different tissues. Our results suggest that crucian carp can reduce the environmental toxicity of As(III) at certain concentrations by transforming it into less toxic forms within their bodies.

Toxicogenomics of the Freshwater Oligochaete, Tubifex tubifex (Annelida, Clitellata), in Acute Water-Only Exposure to Arsenic.

A toxicogenomic approach was used for toxicity evaluation of arsenic in the aquatic environment, and differential gene expression was investigated from 24 h and 96 h water-only acute toxicity tests with the aquatic oligochaete, Tubifex tubifex (Annelida, Clitellata). Several toxicological endpoints (survival and autotomy) of the oligochaete and tissue residues were measured, and dose-response modelling of gene expression data was studied. A reference transcriptome of the aquatic oligochaete, T. tubifex, was reconstructed for the first time, and genes related to cell stress response (Hsc70, Hsp10, Hsp60, and Hsp83), energy metabolism (COX1), oxidative stress (Cat, GSR, and MnSOD), and the genes involved in the homeostasis of organisms (CaM, RpS13, and UBE2) were identified and characterised. The potential use of the genes identified for risk assessment in freshwater ecosystems as early biomarkers of arsenic toxicity is discussed.

A Review of the Effect of Drinking Water Contaminated with Arsenic on Liver Cancer

Arsenic (As) is a highly toxic and carcinogenic element. Drinking water and some foods (for example, rice, cereals, or fruit juices) are major sources of arsenic. Chronic arsenic poisoning, or arsenicosis, causes internal disorders, such as liver damage, as well as cancers. The purpose of this review study was to examine the epidemiological literature on the side effects of arsenic on liver cancer. Initially, 112 articles from January 1, 2000, to March 1, 2023, were found in the mentioned databases. Then, by removing duplicate items, 85 articles entered the stage of examining the title of the articles and removing irrelevant items based on the title of the article. After reviewing the full text of 38 articles, 14 articles were included in the study and used to investigate the effect of arsenic in drinking water on liver cancer. Many environmental pollutants, including arsenic, can cause many diseases in the human body. This metal can generally enter all body organs through the blood circulation system and affect them. The results of previous studies have shown that long-term exposure to arsenic causes disruption in normal liver function (hepatomegaly, sclerosis, fibrosis, and cirrhosis). Various mechanisms have been introduced for arsenic carcinogenesis. Among the important mechanisms that cause liver carcinogenesis by arsenic, the following can be mentioned: disturbance of the balance of liver enzymes, damage to the DNA wall, its destruction, inability to repair DNA, inappropriate function of estrogens, and liver apoptosis.

Phytoremedial Effect Of Ocimum sanctum Against Arsenic Induced Toxicity In Charles Foster Rats

Globally, 300 million people worldwide are exposed to groundwater arsenic poisoning in the recent time, while an estimated 10 million population are exposed to arsenic poisoning in Bihar (India). The arsenic contamination in ground water has caused serious health hazards in the exposed population. The typical symptoms of arsenicosis are observed in the exposed population mostly skin manifestations such as hyperkeratosis, melanosis, loss of appetite, neuro-behavioral disorders etc. Hence, the present study aims to develop novel drug discovery against arsenic induced toxicity in rat models. In the present study treatment groups received sodium arsenite orally at the dose of 8 mg/kg body weight daily for 90 days followed by administration of Ocimum sanctum (Tulsi) seed extract at the dose of 500 mg/ kg body weight daily by gavage method for 60 days. Their biochemical levels like liver and kidney function tests were assayed and were found with elevated levels. Furthermore, their free radical assessment such as lipid peroxidation levels were assayed which was also found to be many folds higher. Furthermore, the arsenic concentration in the tissue of liver and kidney was significantly very high. But, after the administration of ethanolic seed extract of Ocimum sanctum, there was significant restoration in the biochemical and lipid peroxidation levels. Moreover, there was also reduction in the arsenic content in the liver and kidney tissues of rats. The phytoremedial effect of this novel plant (Ocimum sanctum) denotes that it possesses antidote effect against arsenic induced toxicity.

Lysine specific demethylase 1 inhibits sodium arsenite activation of HSCs by regulating SESN2/AMPK/ULK1 signaling pathway activity.

Lysine specific demethylase 1 (LSD1) is a histone demethylase that specifically catalyzes the demethylation of histone H3K4 (H3K4me1/2) and regulates gene expression. In addition, it can mediate the process of autophagy through its demethylase activity. Sestrin2 (SESN2) is a stress-induced protein and a positive regulator of autophagy. In NaAsO2-induced mouse fibrotic livers and activated hepatic stellate cells (HSCs), LSD1 expression is decreased, SESN2 expression is increased, and autophagy levels are also increased. Overexpression of LSD1 and silencing of SESN2 decreased the level of autophagy and attenuated the activation of HSCs induced by NaAsO2. LSD1 promoted SESN2 gene transcription by increasing H3K4me1/2 in the SESN2 promoter region. 3-methyladenine (3-MA) and chloroquine were used to inhibit autophagy of HSCs, and the degree of activation was also alleviated. Taken together, LSD1 positively regulates SESN2 by increasing H3K4me1/2 enrichment in the SESN2 promoter region, which in turn increases the level of autophagy and promotes the activation of HSCs. Our results may provide new evidence for the importance of LSD1 in the process of autophagy and activation of HSCs induced by arsenic poisoning. Increasing the expression and activity of LSD1 is expected to be an effective way to reverse the autophagy and activation of HSCs induced by arsenic poisoning.

Density Functional Theory Calculation May Confirm Arsenic-Thiol Adhesion as the Primary Mechanism of Arsenical Toxicity.

Previously, it was believed that methylation was the body's primary method to detoxify inorganic arsenic. However, recent research has shown that the metabolized intermediate known as MMAIII is more toxic than arsenite and arsenate, contradicting a previous understanding. Another important question arises: is arsenical toxicity truly caused by arsenic binding to proteins through arsenic thiol adhesion? Based on the toxicity order of the experiment, with MMAIII being the most toxic, followed by arsenite, arsenate, DMAV, and MMAV, density functional theory (DFT) calculations can provide a straightforward assessment of this issue. Our practice captures all the transition states associated with a specific imaginary-frequency vibration mode, including proton transfer and simultaneous departure of leaving group. We have obtained the energy barriers for five arsenicals reacting with thiol, alcohol, and amine separately. In addition to energetic favorability, the following are the energy barriers for arsenic's reaction with thiol ranked from low to high: MMAIII (25.4 kcal/mol), arsenite (27.7 kcal/mol), arsenate (32.8 kcal/mol), DMAV (36.2 kcal/mol), and MMAV (38.3 kcal/mol). Results show that the toxicity of arsenicals is mainly caused by their reaction with thiol rather than with alcohol or amine, as supported by the trend of decreasing toxicity and increasing energy barriers. Thus, this DFT calculation may confirm the paradigm that arsenic-thiol adhesion is the primary cause of arsenic toxicity in the body.

Characterisation of arsenic levels in acid-treated arsenic-containing sludge after steel slag-fly ash gel curing

ABSTRACT Arsenic-containing sludge (ABG) is a common hazardous waste in the metallurgical industry and poses a serious threat to environmental safety. However, its instability and mobility have a significant impact on the environment. Traditional curing methods are time-consuming and costly, often resulting in incomplete curing. In this study, we introduce a curing/stabilisation method with a steel slag-fly ash gel material after ABG acid treatment. The toxic leaching of arsenic from ABG was reduced to 220 mg/kg by treating the sludge with acids (H2SO4-H3PO4) at different solid-to-liquid ratios. Afterward, H2O2 was added to oxidise As(III) to As(V). The ABG was cured/stabilised using an alkali-activated steel slag-fly ash gel material. The cured product exhibited optimal arsenic fixation under an ABG/steel slag/fly ash mass ratio of 1:4:2, a curing temperature of 60°C, a curing time of 20 h, and an ambient pH of 12.5. Under these conditions, steel slag-fly ash facilitated Ca-As precipitation, resulting in a hydration reaction that produced C-S-H gel. Additionally, the reaction generated calcium hydroxide, calcium and iron pyroxene, silica, and iron ferrite, which adsorbed part of the free arsenic, completing the curing of the acid-treated ABG and stabilising arsenic leaching toxicity. The leaching of arsenic in the ABG was much lower than the Chinese ‘Hazardous Wastes Leaching Toxicity Identification Standard’ (GB5085.3-2007) (5 mg/L), with an arsenic curing rate exceeding 99%. The mechanism of arsenic solidification involves the combined effects of chemical precipitation, physical encapsulation, and adsorption. Collectively, our findings demonstrated that the use of steel slag-fly ash gel as a functional material for ABG curing holds considerable environmental and economic benefits. Therefore, this study provides theoretical guidance and provides insights into the experimental feasibility of ABG treatment.

Protective and antidote effect of Foeniculum vulgare against Sodium Arsenite induced hepatotoxicity and testicular toxicity in Charles Foster rats

Arsenic poisoning in groundwater is the most common environmental pollutant, which is leading to serious pollution worldwide. Chronic arsenic exposure from drinking water to humans causes major public health-related issues. The present study was conducted to investigate the antidote effects of Foeniculum vulgare (Fennel) against arsenic-induced hepatotoxicity and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm) were divided into four Groups (n=6), where control Group-I received a normal diet and water; Group - II and Group - III received sodium arsenite (8 mg per kg body weight per day) for 90 days. Group III was left with a normal diet and water for the next 60 days for auto-recovery. The group IV rats were administered Foeniculum vulgare (Funnel) hydroxyl ethanolic seed extract at a dose of 150 mg per kg body weight for 60 days in a 90-day pre-treated sodium arsenite group (8 mg per kg body weight). After complete dose duration, all the treated animals were sacrificed the same day for haematological, biochemical, hormonal, and histopathological studies. In the arsenic treated rats, there were significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. And there was also decease in the sperm count and sperm motility, accompanied by an increased incidence of sperm abnormalities and hormonal imbalances leading to infertility. In contrast, after the administration of F. vulgare seeds hydroxy-ethanolic extract to arsenic-treated rats, significant (p<0.001) improvements were observed in hepatic and renal parameters as well as haematological parameters. In the arsenic-intoxicant rat, after administration of F. vulgare seeds hydroxyl ethanolic extract, there was a significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum LPO. The histopathological study also showed the F. vulgare seeds hydroxy-ethanolic extract significantly restored the cellular integrity of testicular cells, leading to their normal functioning against arsenic-induced toxicity.

Ameliorative effect of Calendula officinalis against arsenic induced toxicity in Charles Foster rats

The present study is focused to combat the deleterious effect of arsenic toxicity in animal models utilizing medicinal plant extract. The animals (Charles Foster rats) were treated with Sodium arsenite at the dose of 8 mg per kg body weight for 90 days to make arsenic model and upon these arsenic pre-treated rats leaf extract of Calendula officinalis at the dose of 200 mg per kg body weight was administered for 60 days to study the ameliorative effects of this plant extract. The study shows that arsenic induced toxicity caused deleterious effect on the rats at the haematological, biochemical and histopathological levels and there was significant normalisation in the animal at all the respective levels. Hence, it possesses ameliorative properties against arsenic induced toxicity and can be used for therapeutic purpose.

'Environmental standard limit concentration' arsenic exposure is associated with anxiety, depression, and autism-like changes in early-life stage zebrafish

Arsenic is a worldwide environmental pollutant that can impair human health. Previous studies have identified mental disorders induced by arsenic, but the environmental exposure concentrations in the early life stages associated with these disorders are poorly understood. In the present study, early-life stage zebrafish were used to explore the effects on mental disorders under 'environmental standard limit concentrations' arsenic exposures of 5, 10, 50, 150, and 500 μg/L. The results showed that arsenic exposure at these concentrations changed the locomotor behavior in larval zebrafish and was further associated with anxiety, depression, and autism-like behavior in both larval and juvenile zebrafish. Changes were noted at benchmark dose limit (BMDL) concentrations as low as 0.81 μg/L. Transcriptomics showed that immediate early genes (IEGs) fosab, egr1, egr2a, ier2b, egr3, and jund were decreased after arsenic exposure in larval and juvenile zebrafish. Nervous system impairment and anxiety, depression, and autism-like behaviors in early-life stage zebrafish at 'environmental standard limit concentrations' may be attributed to the downregulation of IEGs. These findings in zebrafish provided new experimental support for an arsenic toxicity threshold for mental disorders, and they suggest that low levels of environmental chemicals may be causative developmental factors for mental disorders.

Response of garlic (Allium sativum L.) to the combined toxicity of microplastics and arsenic

The extensive utilization of mulch films in agricultural settings, coupled with the persistence of microplastic remnants in soil following the natural degradation of plastics, has given rise to detrimental microplastic impacts on crops. Arsenic (As) contamination in the environment is known to accumulate in crops through aquatic pathways or soil. Garlic (Allium sativum L.), a globally popular crop and seasoning, contains alliin, a precursor of its flavor compounds with medicinal properties. While alliin exhibits antimicrobial and antioxidant effects in garlic, its response to microplastics and arsenic has not been thoroughly investigated, specifically in terms of microplastic or As uptake. This study aimed to explore the impact of varied stress concentrations of microplastics on the toxicity, migration, and accumulation of As compounds. Results demonstrated that polystyrene (PS) fluorescent microspheres, with an 80 nm diameter, could permeate garlic bulbs through the root system, accumulating within vascular tissues and intercellular layers. Low concentrations of PS (10 and 20 mg L−1) and As (2 mg L−1) mitigated the production and accumulation of reactive oxygen species (ROS) and antioxidant enzymes in garlic. Conversely, garlic exhibited reduced root vigor, substance uptake, and translocation when treated with elevated As concentrations (4 mg L−1) in conjunction with PS concentrations of 40 and 80 mg L−1. An escalation in PS concentration facilitated As transport into bulbs but led to diminished As accumulation and biomass in the root system. Notably, heightened stress levels weakened garlic's antioxidant defense system, encompassing sulfur allicin and phytochelatin metabolism, crucial for combating the phytotoxicity of PS and As. In summary, PS exerted a detrimental influence on garlic, exacerbating As toxicity. The findings from this study offer insights for subsequent investigations involving Liliaceae plants.

Gut microbiota deficiency aggravates arsenic-induced toxicity by affecting bioaccumulation and biotransformation in C57BL/6J mice

Gut microbiome can influence the arsenic metabolism in mammals. Confusingly, gut microbiome was found to both mitigate and exacerbate arsenic toxicity. In this study, the role of gut microbiota in arsenic bioaccumulation, biotransformation, and organ toxicity in C57BL/6J mice was investigated. Gut microbiota deficiency model was established by antibiotics (Ab) cocktail AVNM. Conventional and gut microbiota deficiency mice were exposed to NaAsO2 for 4 weeks. Comparing with Ab-treated mice, the total arsenic (tAs) in the tissues was significantly reduced in conventional mice, which was opposed to the results of those in feces. Interestingly, dimethyl arsenite (DMA) was the most abundant metabolite in the feces of Ab-treated mice, while arsenic acid (AsV) had the highest proportion in the feces of conventional mice with approximately 16-fold than that in Ab-treated mice, indicating the critical role of gut microbiota in metabolizing arsenious acid (AsIII) to AsV. Additionally, the liver and kidney in Ab-treated mice showed more severe pathological changes and apoptosis. The significant increased level of ionized calcium-binding adapter molecule 1 (IBA-1) was also found in the brains of Ab-treated mice. Our results indicated that gut microbiota protected the host from arsenic-induced toxicity in liver, kidney, and brain by reducing the arsenic accumulation.

Research progress on arsenic, arsenic-containing medicinal materials, and arsenic-containing preparations: clinical application, pharmacological effects, and toxicity.

Introduction: The toxicity of arsenic is widely recognized globally, mainly harming human health by polluting water, soil, and food. However, its formulations can also be used for the clinical treatment of diseases such as leukemia and tumors. Arsenic has been used as a drug in China for over 2,400 years, with examples such as the arsenic-containing drug realgar mentioned in Shennong's Herbal Classic. We have reviewed references on arsenic over the past thirty years and found that research has mainly focused on clinical, pharmacological, and toxicological aspects. Results and Discussion: The finding showed that in clinical practice, arsenic trioxide is mainly used in combination with all-trans retinoic acid (ATRA) at a dose of 10mg/d for the treatment of acute promyelocytic leukemia (APL); realgar can be used to treat acute promyelocytic leukemia, myelodysplastic syndrome, and lymphoma. In terms of pharmacology, arsenic mainly exerts anti-tumor effects. The dosage range of the action is 0.01-80μmol/L, and the concentration of arsenic in most studies does not exceed 20μmol/L. The pharmacological effects of realgar include antiviral activity, inhibition of overactivated lactate dehydrogenase, and resistance to malaria parasites. In terms of toxicity, arsenic is toxic to multiple systems in a dose-dependent manner. For example, 5μmol/L sodium arsenite can induce liver oxidative damage and promote the expression of pro-inflammatory factors, and 15μmol/L sodium arsenite induces myocardial injury; when the concentration is higher, it is more likely to cause toxic damage.

Soil Microbiomes and their Arsenic Functional Genes in Chronically High-Arsenic Contaminated Soils.

Microbial arsenic transformations play essential roles in controlling pollution and ameliorating risk. This study combined high-throughput sequencing and PCR-based approaches targeting both the 16S rRNA and arsenic functional genes to investigate the temporal and spatial dynamics of the soil microbiomes impacted by high arsenic contamination (9.13 to 911.88mg/kg) and to investigate the diversity and abundance of arsenic functional genes in soils influenced by an arsenic gradient. The results showed that the soil microbiomes were relatively consistent and mainly composed of Actinobacteria (uncultured Gaiellales and an unknown_67 - 14 bacterium), Proteobacteria, Firmicutes (particularly, Bacillus), Chloroflexi, and Acidobacteria (unknown_Subgroup_6). Although a range of arsenic functional genes (e.g., arsM, arsC, arrA, and aioA) were identified by shotgun metagenomics, only the arsM gene was detected by the PCR-based method. The relative abundance of the arsM gene accounted for 0.20%-1.57% of the total microbial abundance. Combining all analyses, arsenic methylation mediated by the arsM gene was proposed to be a key process involved in the arsenic biogeochemical cycle and mitigation of arsenic toxicity. This study advances our knowledge about arsenic mechanisms over the long-term in highly contaminated soils.