Density Functional Theory (DFT) Investigation of The Oxidative Degradation of NaAsO2 Via Hydroxyl Radical

Arsenic is an environmentally ubiquitous health hazard due to its toxicity combined with its natural abundance and heavy industrial applications. Due to its role in cardiovascular disease, neurotoxicity, and various cancers, it is important to understand environmental fate of arsenic-containing compounds to take steps towards remediation. Sodium arsenite (NaAsO2) is one such compound that has been used worldwide as an herbicide, rodenticide, and insecticide. It is also toxic by ingestion, inhalation, and skin absorption. In aqueous environments arsenite (As(III))-containing compounds can be oxidized to the less-toxic arsenate (As(V)) form. We have investigated the oxidation of sodium arsenite in water solution at the density functional theory level using the Minnesota 06 hybrid (M06-2X) functional and Pople basis sets (6-31G(d,p) and 6-311G(d,p)) with polarizable continuum model (PCM) solvation approach. Our computational results indicate that the oxidation mechanism of NaAsO2 by hydroxyl radical proceeds via sequential addition reactions where sodium arsenite (III) converts to sodium arsenate (V) via an arsenic (IV) intermediate.

Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study

The purpose of this study is to understand the mechanism of sodium arsenite (NaAsO2)-induced apoptosis of L-02 human hepatic cells, and how Dictyophora polysaccharide (DIP) protects L-02 cells from arsenic-induced apoptosis. The results revealed that DIP pretreatment inhibited NaAsO2 induced L-02 cells apoptosis by increasing anti-apoptotic Bcl-2 expression and decreasing pro-apoptotic Bax expression. Proteomic analysis showed that arsenic treatment disrupted the expression of metabolism and apoptosis associated proteins, including ribosomal proteins (RPs). After pretreatment with DIP, the expression levels of these proteins were reversed or restored. For the first time, it was observed that the significant decrease of cytoplasmic RPs and the increase of mitochondrial RPs were related to human normal cell apoptosis induced by arsenic. This is also the first report that the protective effect of DIP on cells was related to RPs. The results highlight the relationship between RPs and apoptosis, as well as the relationship between RPs and DIP attenuating arsenic-induced apoptosis.

Sodium Arsenite Induces Bronchial Epithelial Cell Cancer With Mitochondrial Dysfunction by Affecting Cell Cycle

Background: Arsenide, a kind of pollution widely existing in the environment, and the mechanism of occurrence and development of lung cancer leading by long-term arsenic exposure still needs further research up to present. We investigated how high and low doses of arsenic induce human bronchial epithelial cell transformation and the molecular mechanisms involvedMethods: After exposing human bronchial epithelial cells(Beas-2B) to different doses of sodium arsenite for 24 h, RNA-seq analysis was performed to detect arsenic-regulated genes; for cell viability and status and for cell cycle changes and mitochondrial function; long-term exposure to 1μM sodium arsenite after 20 consecutive passages for cell cycle changes and mitochondrial function.Results: In the study, human bronchial epithelial cells were exposed to varying high-dose sodium arsenite in short term or treated with low dose in a long term, and the data showed that both short and long terms treatment promoted G1/S transition of Beas-2B cells, inducing significant increases of expression of AKAP95, cyclin D1, cyclin D2 and cyclin E1. However, silencing AKAP95 by treating cells with siAKAP95 showed a protective function that inhibited G1/S transition, suggesting that regulatory mechanism of AKAP95 on cell cycle during cell malignant transformation induced by sodium arsenite. In addition, we also noticed some mitochondrial dysfunctions occurred during sodium arsenite exposure, including the disappearance of mitochondrial double membrane structure, the formation of vacuole structure, the decrease of mitochondrial membrane potential, the change of expression levels of mitochondrial related proteins Tim22, Tim23, Tom40 and OPA1, the release of lactate dehydrogenase (LDH) and the decrease of reduced glutathione.Beas-2B cells, which exposed to low-dose sodium arsenite for a long term, were subcultured for 20 generations, and it was found that the exposure time was positively proportional to the growth and migration rate of cells. The exposed cells were used in tumor bearing transplantation experiment (mice), and results showed that the longer the exposure time, the faster the tumor volume growth rate of As-Beas-2B cells. Tumor tissues were taken out for HE staining, and it was found that the cell morphology changed and the volume increasedConclusion: high and low doses of sodium arsenite induced malignant transformation of human bronchial epithelial cells by promoting G1/S turnover through AKAP95 with associated cyclins, accompanied by the development of mitochondrial dysfunction.

Therapeutic effect of fenugreek (Trigonella foenum-graecum) seeds extract against arsenic induced toxicity in Charles Foster rats

The prime objective of the present study was to establish fenugreek (Trigonella foenum-graecum L.) seeds extract as an antidote against arsenic induced hepato-renal toxicity in rats. The male Charles Foster rats (weighing 160-180 g) were selected to make arsenic intoxicated model. The arsenic treated group of rats were orally treated with sodium arsenite at the dose of 8 mg/kg body weight/day for 90 days. Thereafter, the arsenic pretreated rats were further administered with fenugreek ethanolic seeds extract at the dose of 250 mg/kg body weight/day for 90 days. After the completion of the treatment, animals of all the groups were sacrificed for the biochemical and histopathological estimation. The arsenic treated rats showed significant (p < 0.0001) alterations at the various hepatic and renal biomarker parameters and at serum MDA levels in comparison to the control rats. Significant (p < 0.0001) arsenic accumulation was also observed in the blood, liver and kidney tissues of the arsenic treated rats. However, after the administration with fenugreek seeds extract, significant (p < 0.0001) restoration was observed in the liver and kidney biomarker parameters and at haematological variables. Fenugreek seeds extract administration also significantly (p < 0.0001) reduced the serum MDA levels and arsenic concentration levels in blood, liver and kidney tissues, along with considerable restorations at the cellular architecture of liver and kidney tissues. The study concluded that fenugreek seeds possessed potential hepato-renal ameliorative effect against sodium arsenite induced toxicity in rats, and can be used for its therapeutic value against arsenic poisoning.