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Contamination of drinking water by carcinogen arsenic (As) is of worldwide concern as its exposure poses potential threat to human health. As such, it is important to understand the mechanisms associated with As-induced toxicity to humans. The Nrf2/Keap1 signal pathway is one of the most important defense mechanisms in cells to counter oxidative stress; however, limited information is available regarding its role in countering As-induced stress in model animal mouse. In this study, we assessed the responses of Nrf2/keap1 pathway in mice after chronic exposure to As at environmentally-relevant concentrations of 10-200 μg L -1 for 30 days via drinking water. Our results indicate that chronic As exposure had limited effect on mouse growth. However, As induced oxidative stress to mice as indicated by increased content of malondialdehyde (MDA; 52-90%), an index of lipid peroxidation. Further, arsenic exposure reduced the activity of superoxide dismutase (SOD; 14-18%), an indication of reduced anti-oxidative activity. Besides, arsenic exposure increased MnSOD mRNA transcription by 25-66%, and decreased the mRNA transcriptions of Cu/ZnSOD by 72-83% and metallothionein by 16-75%, a cysteine-rich protein involved in metal detoxification. To counter arsenic toxicity, the expression of transcription factor for Nrf2 and Keap1 was increased by 2.8-8.9 and 0.2-8.1 fold in mice. To effectively reduce As-induced oxidative stress, the Nrf2/Keap1 transcription factor upregulated several downstream anti-oxidative genes, including heme oxygenase-1 (0.9-2.5 fold), glutamate-cysteine ligase catalytic subunit (0.6-1.7 fold), and NADH quinone dehydrogenase 1 (2.1-4.8 fold). This study shows the importance of Nrf2/Keap1 signaling pathway and associated anti-oxidative enzymes in countering As-toxicity in mice, possibly having implication for human health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 μg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 μg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Hand-to-mouth activity is an important pathway for children's exposure to contaminated soils, which is often co-contaminated by Pb and As in mining and smelting sites. To reduce soil Pb risk to humans by oral exposure, phosphate amendments have been used to reduce Pb relative bioavailability (RBA), but its efficiency has not been investigated using validated in vitro assays nor its influence on As-RBA. Here, 5 contaminated soils (A-E) were amended with 0.5% phosphoric acid (PA) to study its effect on Pb- and As- RBA using a newly-developed mouse kidney model and bioaccessibility using 4 in vitro assays including UBM, SBRC, IVG, and PBET. Based on the mouse kidney model, Pb-RBA in PA-amended soils decreased from 14.2-62.5% to 10.1-29.8%. In contrast, As-RBA decreased from 26.5% to 15.9% in soil B but increased from 27.5 to 41.2% in soil D, with changes being insignificant in 3 other soils (35.8-58.8 to 28.1-61.1%). When assessing Pb bioaccessibility in PA-amended soils, decreased bioaccessibility were found using PBET and SBRC. For As, its bioaccessibility increased in PA-amended soils, inconsistent with in vivo data. Our results shed light on the importance of method selection to assess risk in Pb- and As-contaminated soils amended with phosphate., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A steady-state mouse model was developed to determine arsenic (As) relative bioavailability (RBA) in rice to refine As exposure in humans. Fifty-five rice samples from 15 provinces of China were analyzed for total As, with 11 cooked for As speciation and bioavailability assessment. Arsenic concentrations were 38-335 μg kg -1 , averaging 133 μg kg -1 , with As III being dominant (36-79%), followed by DMA V (18-58%) and As V (0.5-16%). Following oral doses of individual As species to mice at low As exposure (2.5-15 μg As per mouse) over a 7-d period, strong linear correlations (R 2 = 0.99) were observed between As urinary excretion and cumulative As intake, suggesting the suitability and sensitivity of the mouse bioassay to measure As-RBA in rice. Urinary excretion factor for DMA V (0.46) was less than inorganic As (0.63-0.69). As-RBA in cooked rice ranged from 13.2 ± 2.2% to 53.6 ± 11.1% (averaging 27.0 ± 12.2%) for DMA V and 26.2 ± 7.0% to 49.5 ± 4.7% (averaging 39.9 ± 8.3%) for inorganic As. Calculation of inorganic As intake based on total inorganic As in rice overestimated As exposure by 2.0-3.7 fold compared to that based on bioavailable inorganic As. For accurate assessment of the health risk associated with rice consumption, it is important to consider As bioavailability especially inorganic As in rice.

Due to its toxicity as a carcinogen and wide distribution in the environment, arsenic (As) exposure in humans is of public concern globally. Many studies have manifested that As exposure induces cancers besides pathological effects in humans. Animal studies showed that chronic As exposure induces serious neurological effects. Based on recent studies, researchers proposed that As, including arsenate (AsV) and arsenite (AsIII), is also an endocrine disruptor. This review discusses the mechanisms of As toxicity on three endocrine systems including gonadal, adrenal and thyroid endocrine systems. Arsenic methylation and oxidative stress are responsible for As-induced disorders of endocrine systems, however, strong binding of AsIII to thiols also play an important role. Some studies showed AsV toxicity on endocrine systems, but mechanistic investigation is lacking. Research is needed to look into their toxicity mechanisms to help cure the illnesses caused by As-induced endocrine system disorders., (Published by Elsevier Ltd.)

Arsenic (As) contamination in aquatic environment adversely impacts aquatic organisms. The present study assessed the toxicity of different As species and concentrations on bighead carp (Hypophthalmichthys nobilis) at early life stage, a major fish in Yangtze River, China. We measured the changes in embryo and larvae survival rate, larvae aberration, concentrations of thyroid hormone thyroxine, and transcription levels of thyroid hormone receptors (TRs) in fish larvae after exposing to arsenite (AsIII) or arsenate (AsV) at 0, 10, 30, 50, 100, or 150 μg L(-1) for 78 h. As concentrations ≤ 150 μg L(-1) had limited effect on embryo survival rate (6-8% inhibition), but larvae survival rate decreased to 53-57% and larvae aberration rate increased to 20-24% after As exposure. Moreover, thyroxine levels elevated by 23% and 50% at 100 μg L(-1) AsIII and 150 μg L(-1) AsV. Besides, AsIII and AsV decreased the transcriptional levels of TRα by 72 and 53%, and TRβ by 91 and 81% at 150 μg L(-1) As. Our data showed that AsIII and AsV had limited effect on carp embryo survival, but they were both toxic to carp larvae, with AsIII showing more effect than AsV. As concentrations <150μg L(-1) adversely influenced the development of bighead carp larvae and disturbed their thyroid hormone homeostasis., (Published by Elsevier B.V.)

Different animals and biomarkers have been used to measure the relative bioavailability of arsenic (As-RBA) in contaminated soils. However, there is a lack of As-RBA comparison based on different animals (i.e., swine and mouse) and biomarkers [area under blood As concentration curve (AUC) after a single gavaged dose vs steady-state As urinary excretion (SSUE) and As accumulation in liver or kidney after multiple doses via diet]. In this study, As-RBA in 12 As-contaminated soils with known As-RBA via swine blood AUC model were measured by mouse blood AUC, SSUE, and liver and kidney analyses. As-RBA ranges for the four mouse assays were 2.8-61%, 3.6-64%, 3.9-74%, and 3.4-61%. Compared to swine blood AUC assay (7.0-81%), though well correlated (R(2) = 0.83), the mouse blood AUC assay yielded lower values (2.8-61%). Similarly, strong correlations of As-RBA were observed between mouse blood AUC and mouse SSUE (R(2) = 0.86) and between urine, liver, and kidney (R(2) = 0.75-0.89), suggesting As-RBA was congruent among different animals and end points. Different animals and biomarkers had little impact on the outcome of in vivo assays to validate in vitro assays. On the basis of its simplicity, mouse liver or kidney assay following repeated doses of soil-amended diet is recommended for future As-RBA studies.

Rice can take up and translocate more As and Hg than other cereal crops. A hydroponic experiment was conducted to investigate their interactive effects on their uptake and toxicity in rice seedling after exposing to As(III) (0.1, 0.5 or 2.5 mg L−1) and Hg (0.05, 0.25 or 1.25 mg L−1) for 14 d. Rice was much more effective in taking up Hg than As and sequestered both in the roots. As and Hg reached 339 and 433 mg kg−1 in the roots, and 48.5 and 16.1 mg kg−1 in the shoots at As2.5 + Hg1.25. Though Hg inhibited As uptake and translocation, it enhanced As(III) toxicity to rice seedling. However, As inhibited Hg uptake at Hg0.05, but the opposite was observed at Hg0.25 and Hg1.25. Arsenite (54–100%) and inorganic Hg (100%) were the predominant form in the plant based on speciation analysis via HPLC–ICP–MS. Malondialdehyde in the roots and shoots increased with increasing As and Hg concentrations, with the highest being 54 μmol g−1 at As0.5 + Hg1.25 in the roots. Root cell structural damage and organelles number reduction with increasing As and Hg concentration were observed based on TEM. As and Hg transformation and toxicity can help to understand the metabolic mechanisms of As and Hg in rice plant when co-present.

Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and genotoxicity in humans, with reactive oxygen species playing an important role. While As induces adverse effects by decreasing DNA methylation and affecting protein 53 expression, Se induces adverse effects by modifying thioredoxin reductase. However, they can react with glutathione and S-adenosylmethionine by forming an As-Se complex, which can be secreted extracellularly. We hypothesize that there are two types of interactions between As and Se. At low concentration, Se can decrease As toxicity via excretion of As-Se compound [(GS3)2AsSe](-), but at high concentration, excessive Se can enhance As toxicity by reacting with S-adenosylmethionine and glutathione, and modifying the structure and activity of arsenite methyltransferase. This review is to summarize their toxicity mechanisms and the interaction between As and Se toxicity, and to provide suggestions for future investigations., (Published by Elsevier Ltd.)

Abstract Low concentrations of arsenic (As) contamination in aquatic environment is a worldwide issue, which is of great concern. To evaluate the impact of low concentrations of As on zebrafish, we measured the growth, antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), oxidative damage (malondialdehyde, MDA) and apoptosis-related genes (nrf2 , p53 and c-jun) of adult zebrafish after exposing to different AsIII concentrations (0, 10, 50, 100 or 150 μg L−1) for 28 d. Results indicated that exposure to low AsIII concentrations decreased the zebrafish weight by 14%, increased the activities of SOD and CAT by 23–41% and 31–59%, decreased the contents of MDA by 29–54%, and modulated transcription of apoptosis related genes. Our study showed that chronic exposure to AsIII concentrations <150 μg L−1 generated oxidative stress and damage on zebrafish, and altered apoptosis-related genes in zebrafish. Graphical abstract Image Highlights • Our study demonstrated the toxic effect of low concentrations of arsenite on zebrafish. • Exposure to low concentration arsenite can decrease the growth of zebrafish. • Exposure to low concentration arsenite can cause oxidative stress and damage on zebrafish. • Exposure to low concentration arsenite can disrupt the transcriptional levels of apoptosis-related genes (nrf2, p53 and c-jun). [ABSTRACT FROM AUTHOR]