Sodium Arsenite Research Articles

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.

Effect of Ethanolic Stem Extract of Nelsonia Canescens on Selected Biochemical Parameters in Male Wistar Rats Induced with Sodium Arsenite

Medicinal plants are those that have curative qualities or have positive pharmacological effects on the human body. The effect of ethanolic stem extracts from Nelsonia canescens was studied in relation to Sodium arsenite-induced toxicity in wistar rats. Fresh stem extract of Nelsonia canescens were obtained behind rice mill area, Wukari, Taraba state and was shade dried at room temperature and was homogenized into powder and measured at 300g into 100ml of absolute ethanol for 72 hours. 15 healthy male rats of 70g to 90g weight were obtained from animal house Makurdi, Benue state. Animals from Group 1 were used as control. 5mg/kg body weight of Sodium arsenite was administered to Group 2 animals while animals in Groups 3, 4 and 5 were administered with Nelsonia canescens ethanolic stem extracts 50 mg/kg, 100mg/kg and 200 mg/kg as well. At the end of 3 weeks the animals were sacrificed and serum sample were collected and analysed using standard methods. The results indicate that, when compared to those who received Sodium arsenite, those who received ethanol stem extracts of Nelsonia canescens showed a comparatively considerable liver protection against Sodium arsenite -induced damage. The levels of biochemical parameters: Albumin, Total protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin, Urea, Creatinine of rats administered with Sodium arsenite only was also observed. The Nelsonia canescens extract’s activity at 200mg/kg bw (higher dose) give a reasonable decrease in the amount of these liver enzymes. Deducing from study results, it indicates that Nelsonia canescens leaf extracts could be an effective agent in Sodium arsenite mediated liver toxicity in adult wistar rats and drug development.

Protective Effect of Citicoline on Sodium Arsenite-Induced Nephrotoxicity in Mice

Background: Sodium arsenite (NaAsO2) is a common mineral contaminant in drinking water in numerous parts of the world. It has been shown to have cardiovascular, metabolic, neuroendocrine, and urinary effects on the body. There is abundant scientific evidence that establishes a strong correlation between arsenic exposure and kidney-related disorders. Objectives: The present study aimed to investigate the potential protective effect of citicoline against NaAsO2-induced nephrotoxicity. Methods: The groups included a control group, a group treated with NaAsO2 at a concentration of 50 ppm, a group treated with Cit at a dosage of 1000 mg/kg, and three groups of NaAsO2 (50 ppm) co-treated with Cit at doses of 250, 500, and 1000 mg/kg, respectively. Results: Citicoline decreased the level of blood urea nitrogen (P < 0.001), creatinine levels (P < 0.001), thiobarbituric acid reactive substances (P < 0.001), nitric oxide (P < 0.001), inflammatory factors tumor necrosis factor-α (P < 0.001) and interleukin-6 (P < 0.001 and P < 0.001). Furthermore, Cit increased total thiol (P < 0.001) and activity levels of catalase (P < 0.05 and P < 0.001), superoxide dismutase (P < 0.01 and P < 0.001), and glutathione peroxidase (P < 0.001). Therefore, Cit reduced the harmful effects caused by the imbalance in oxidative and antioxidant systems and histopathological damage in NaAsO2-intoxicated mice, improving the damage caused by oxidative stress and inflammation. Conclusions: Our research shows that Cit can protect the kidneys against the damaging effects of NaAsO2 by using its antioxidant and anti-inflammatory properties.

Short-term effects of sodium arsenite (AsIII) and sodium arsenate (AsV) on carbohydrate metabolism in the perfused rat liver

The actions of arsenite and arsenate on carbohydrate metabolism in the once-through perfused rat liver were investigated. The compound inhibited lactate gluconeogenesis with an IC50 of 25 µM. It also increased glycolysis and fructolysis at concentrations between 10 and 100 µM. This effect was paralleled by strong inhibition of pyruvate carboxylation (IC50 = 4.25 µM) and by a relatively moderate diminution in the ATP levels. The inhibitory action of arsenate on pyruvate carboxylation and lactate gluconeogenesis was 103 times less effective than that of arsenite. For realistic doses and concentrations («1 mM), impairment of metabolism by arsenate can be expected to occur solely after its reduction to arsenite. Arsenite, on the other hand, can be regarded as a strong short-term modifier of lactate gluconeogenesis and other pathways. The main cause of the former is inhibition of pyruvate carboxylation, a hitherto unknown effect of arsenic compounds.

Regulation of stress granule formation in human oligodendrocytes

Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.

Chronic arsenic exposure affects stromal cells and signaling in the small intestine in a sex-specific manner.

Arsenic is a toxicant that is ingested through drinking water and food, exposing nearly 140 million people to levels above the 10 ppb guideline concentration. Studies have shown that arsenic affects intestinal stem cells (ISCs), but the mechanisms by which arsenic alters the formation of adult cells in the small intestine are not well understood. Signals derived from intestinal stromal cells initiate and maintain differentiation. The goal of this study is to evaluate arsenic's effect on intestinal stromal cells, including PdgfrαLo trophocytes, located proximal to the ISCs, and PdgfrαHi telocytes, located proximal to the transit-amplifying region and up the villi. Adult Sox9tm2Crm-EGFP mice were exposed to 0, 33, and 100 ppb sodium arsenite in their drinking water for 13 weeks, and sections of duodenum were examined. Flow cytometry indicated that arsenic exposure dose-responsively reduced Sox9+ epithelial cells and trended toward increased Pdgfrα+ cells. The trophocyte marker, CD81, was reduced by 10-fold and 9.0-fold in the 100 ppb exposure group in male and female mice, respectively. Additionally, a significant 2.2- to 3.1-fold increase in PdgfrαLo expression was found in male mice in trophocytes and Igfbp5+ cells. PdgfrαHi protein expression, a telocyte marker, was more prevalent along the villus/crypt structure in females, whereas Gli1 expression (telocytes) was reduced in male mice exposed to arsenic. Principle coordinate analysis confirmed the sex-dependent response to arsenic exposure, with an increase in trophocyte and decrease in telocyte marker expression observed in male mice. These results imply that arsenic alters intestinal mesenchymal cells in a sex-dependent manner.

Protective Effect of Heteroxenia fuscescens Extract against Sodium Arsenite-induced Infertility in Male Rats

Background: Arsenic is a potent environmental toxin with dangerous effects on human and animal populations. Heteroxenia fuscescens (H. fuscescens) extract exhibits potential health effects. The purpose of this study was to assess the protective effect of H. fuscescensextract against sodium arsenite-induced infertility and toxicity in rats. Methods: Forty male rats were separated into four groups as follows: control group (2% DMSO, orally), sodium arsenite (10 mg/kg, orally), sodium arsenite + H. fuscescens extract (60 mg/kg in 2% DMSO), and H. fuscescens extract (60 mg/kg in 2% DMSO). Results: GC/MS analysis of H. fuscescens indicates the presence of 10 compounds at retention times of 6.00, 12.53, 19.04, 24.60, 28.56, 35.66, 38.99, 45.29, 48.02, and 52.14. fuscescens extract improves levels of sperm count (53.33 ± 1.52), motility (43.00 ± 1.10), FSH ( 2.17 ± 0.04), LH (2.43 ± 0.06), testosterone (1.87 ± 0.02), and testis weight (0.49 ± 0.01). The antioxidant activity of H. fuscescens extract was reported by a significant decrease in MDA (1.02 ± 0.01) and NO (520.39 ± 14.99) levels, while it significantly increased levels of GSH (1.77 ± 0.07), and CAT (71.38 ± 3.45). Histopathological alterations of the testes, liver, and kidney observed with sodium arsenite have been improved in the treatment group. Conclusion: Heteroxenia fuscescens is beneficial in restoring male sex hormone levels, maintaining a healthy sperm profile, and reducing oxidative stress, all of which lead to an improvement in male rat fertility.

Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells.

Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response-the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative stress. In this work, we examined the modulation of integrated stress responses by OC43 and demonstrated that the negative feedback regulator of eIF2α phosphorylation GADD34 is strongly induced in infected cells. However, the upregulation of GADD34 expression induced by OC43 was independent from the activation of the integrated stress response and was not required for the inhibition of eIF2α phosphorylation in virus-infected cells. Our work reveals a complex interplay between the common cold coronavirus and the integrated stress response, in which efficient viral protein synthesis is ensured by the inhibition of eIF2α phosphorylation but the GADD34 negative feedback loop is disrupted.

Prenatal arsenite exposure alters maternal cardiac remodeling during late pregnancy

Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6 J mice were exposed to 0 (control), 100 or 1000 μg/L sodium arsenite (NaAsO2) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that maternal heart size was smaller and transcript levels of Esr1 (estrogen receptor alpha), Pgrmc1 (progesterone receptor membrane component 1) and Pgrmc2 (progesterone receptor membrane component 2) reduced during late pregnancy with exposure to 1000 μg/L iAs vs. non-exposed pregnant controls. Both 100 and 1000 μg/L iAs also reduced transcription of Nppa (atrial natriuretic peptide). Akt protein expression was also significantly reduced after 1000 μg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events.

Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance.

YPEL2 is a member of the evolutionarily conserved YPEL family involved in cellular proliferation, mobility, differentiation, senescence, and death. However, the mechanism by which YPEL2, or YPEL proteins, mediates its effects is largely unknown. Proteins perform their functions in a network of proteins whose identities, amounts, and compositions change spatiotemporally in a lineage-specific manner in response to internal and external stimuli. Here, we explored interaction partners of YPEL2 by using dynamic TurboID-coupled mass spectrometry analyses to infer a function for the protein. Our results using inducible transgene expressions in COS7 cells indicate that proximity interaction partners of YPEL2 are mainly involved in RNA and mRNA metabolic processes, ribonucleoprotein complex biogenesis, regulation of gene silencing by miRNA, and cellular responses to stress. We showed that YPEL2 interacts with the RNA-binding protein ELAVL1 and the selective autophagy receptor SQSTM1. We also found that YPEL2 localizes stress granules in response to sodium arsenite, an oxidative stress inducer, which suggests that YPEL2 participates in stress granule-related processes. Establishing a point of departure in the delineation of structural/functional features of YPEL2, our results suggest that YPEL2 may be involved in stress surveillance mechanisms.

Synergistic Effects of Vitamin A and Spirulina on Arsenic Load in Rat Tissues and Blood

Arsenic (As) is found in contaminated groundwater as the source of pollution. In this study, 60 Long-Evans rats were used to assess the levels of As in the blood and organs and to compare the effectiveness of vitamin A and spirulina (Spirulina platensis) in preventing a chronic As accumulation. Twelve rats were assigned to each group of animals. The experimental groups were the control (T0), As (T1), As + spirulina (T2), As + vitamin A (T3), and As + spirulina + vitamin A (T4). The T1, T2, T3, and T4 groups were orally administered with sodium arsenite (NaAsO2) @ 4 mg/kg body weight (BW) for 63 days. In addition to NaAsO2, the T2 and T4 received 1 g/kg BW spirulina. The T3 and T4 received 2500 IU/kg BW vitamin A for 63 days, respectively. Four rats were euthanized in each group to evaluate the As concentration in the liver, lung, kidney, and blood at an interval of 21 days. Total As concentration was quantified from the organs using Hydride Generation Atomic Absorption Spectrophotometer (HG-AAS). The results revealed that the T0 had no visible clinical symptoms. However, after 63 days of treatment, the T1 (As only administration) accumulated more As compared to other groups. The concentration of As was highest in the blood, then in the kidney, liver, and lung. In this case, spirulina and vitamin A substantially (p<0.01) decreased the concentration of As in the rats' organs and tissues Spirulina is more effective than vitamin A in reducing As accumulation in rats. In summary, the combination of both spirulina and vitamin A has a positive impact on reducing the accumulation of chronic arsenicosis in rats compared to the individual administration of either spirulina or vitamin A alone. Vol. 10, No. 3, December 2023: 341-351

African swine fever virus maintains de novo global cellular protein synthesis and inhibits stress granules formation via dephosphorylating eIF2α

African swine fever virus (ASFV) has caused enormous economic losses since its first reported detection, and there is still no effective vaccines or drug treatment. During infection, viruses may employ various strategies, such as regulating the host endoplasmic reticulum stress/unfolded protein response or the formation of stress granules (SGs), to form an optimal environment for virus replication. However, how ASFV infection regulates host endoplasmic reticulum stress, eIF2α-regulated protein synthesis, and the formation of SGs remains unclear. Here, we evaluated the activation of ER stress and its three downstream axes during ASFV infection and identified a powerful dephosphorylation of eIF2α by ASFV ex vivo. This strong dephosphorylation property could maintain the efficiency of eIF2α-mediated de novo global protein synthesis, thus ensuring efficient viral protein synthesis at early stage. In addition, the powerful dephosphorylation of eIF2α by ASFV upon infection could also inhibit the formation of SGs induced by sodium arsenite. In addition, a specific eIF2α dephosphorylation inhibitor, salubrinal, could partially counteract ASFV-mediated eIF2α dephosphorylation and inhibit viral replication. Our results provide new insights into the areas of ASFV`s escape from host immunity and hijacking of the host protein translation system.

Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic.

The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure.

Evaluation of Salvia hispanica as a Therapeutic Agent against Sodium Arsenic-Induced Testicular Toxicity in a Male Rats Model.

Chia seeds offer therapeutic properties that aid in the prevention of a variety of ailments, including cardiovascular disease, diabetes, obesity, and other risk factors. Arsenite, a common environmental chemical, has been identified as a reproductive toxin owing to its negative effects on male reproductive health. It has been shown to inhibit spermatogenesis and generate androgenic effects in men. The primary goal of this research was to look into the effect of Salvia hispanica on testicular toxicity caused by sodium arsenite in male rats. A set of 36 male albino rats was allocated to a negative control cohort. The individuals in this group were given a basic meal and orally given distilled water for a duration of 28 days. The other five groups were given a regular meal and received intra-peritoneal injections of sodium arsenite (NaAsO2) at a concentration of 4 mg/kg body weight that was diluted in a 0.9% NaCl solution. The injections were administered consecutively, with two doses given within a two-day period. Subsequently, the rats were categorized into several groups using the following classification: Group 2 consisted of a positive control cohort, in which the rats were given a typical baseline diet. Groups 3, 4, 5, and 6 were given a basic diet that included varying proportions of ground chia seeds, namely 5%, 10%, 15%, and 20% per 100 g of the diet. After the trial was completed, the rats were euthanized, and further biological examination was conducted. The measurements of the reproductive organs were documented and reported. The research assessed the following characteristics: sperm count, motility, progressive motility, and normal morphology. The research included examining serum sex hormones, namely luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. An evaluation of the activity of antioxidant enzymes was performed in the tissue of the testicles. There were statistically significant improvements in the sperm parameters, serum sex hormone levels, and the activity of antioxidant enzymes, such as GPX, SOD, and CAT, in the therapy groups. The levels of malondialdehyde (MDA) exhibited a noteworthy decrease (p ≤ 0.05) when compared to the positive control group. Salvia hispanica seeds have demonstrated a significant level of effectiveness in reducing sodium arsenite-induced testicular toxicity, which leads to the conclusion. The flavonoid content and antioxidant properties of Salvia hispanica seeds may be to blame for the observed behavior. These indicated characteristics may have therapeutic significance in treating testicular harm induced by arsenite exposure.

Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway.

In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods. In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed. The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities. In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA.

Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways.

This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days. As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality. ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.

Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways.

Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.

Chronic arsenic exposure-provoked biotoxicity involved in liver-microbiota-gut axis disruption in chickens based on multi-omics technologies

IntroductionArsenic has been ranked as the most hazardous substance by the U.S. Agency for Toxic Substances and Disease Registry. Environmental arsenic exposure-evoked health risks have become a vital public health concern worldwide owing to the widespread existence of arsenic. Multi-omics is a revolutionary technique to data analysis providing an integrated view of bioinformation for comprehensively and systematically understanding the elaborate mechanism of diseases. ObjectivesThis study aimed at uncovering the potential contribution of liver-microbiota-gut axis in chronic inorganic arsenic exposure-triggered biotoxicity in chickens based on multi-omics technologies. MethodsForty Hy-Line W-80 laying hens were chronically exposed to sodium arsenite with a dose-dependent manner (administered with drinking water containing 10, 20, or 30 mg/L arsenic, respectively) for 42 d, followed by transcriptomics, serum non-targeted metabolome, and 16S ribosomal RNA gene sequencing accordingly. ResultsArsenic intervention induced a serious of chicken liver dysfunction, especially severe liver fibrosis, simultaneously altered ileal microbiota populations, impaired chicken intestinal barrier, further drove enterogenous lipopolysaccharides translocation via portal vein circulation aggravating liver damage. Furtherly, the injured liver disturbed bile acids (BAs) homoeostasis through strongly up-regulating the BAs synthesis key rate-limiting enzyme CYP7A1, inducing excessive serum total BAs accumulation, accompanied by the massive synthesis of primary BA—chenodeoxycholic acid. Moreover, the concentrations of secondary BAs—ursodeoxycholic acid and lithocholic acid were markedly repressed, which might involve in the repressed dehydroxylation of Ruminococcaceae and Lachnospiraceae families. Abnormal BAs metabolism in turn promoted intestinal injury, ultimately perpetuating pernicious circle in chickens. Notably, obvious depletion in the abundance of four profitable microbiota, Christensenellaceae, Ruminococcaceae, Muribaculaceae, and Faecalibacterium, were correlated tightly with this hepato-intestinal circulation process in chickens exposed to arsenic. ConclusionOur study demonstrates that chronic inorganic arsenic exposure evokes liver-microbiota-gut axis disruption in chickens and establishes a scientific basis for evaluating health risk induced by environmental pollutant arsenic.

Ameliorative effect of Ganoderma lucidum on sodium arsenite induced toxicity in Charles Foster rats

Ameliorative effect of Ganoderma lucidum on sodium arsenite induced toxicity in Charles Foster rats

Therapeutic effect of Citrullus lanatus against Sodium arsenite induced reproductive toxicity in Charles Foster rats

Therapeutic effect of Citrullus lanatus against Sodium arsenite induced reproductive toxicity in Charles Foster rats