Gut microbiome disruption impairs arsenic biotransformation and exacerbates toxicity in the water flea Daphnia magna.

Exploring a critical time window for FOXM1-driven bladder injury in chronic arsenic exposure.

Long-term arsenic exposure causes epithelial-mesenchymal transition and kidney fibrosis accompanied by renal lipid metabolic disorders.

Vitamin K2 (MK7) alleviates arsenic-induced cardiac hypertrophy by suppressing the EGR3/BOK mitochondrial apoptosis pathway.

Study on the effects and molecular mechanisms of arsenic-induced kidney damage in mice.

To evaluate the effects of chronic occupational arsenic exposure on thyroid homeostasis and endothelial dysfunction using an integrated biomarker approach. This cross-sectional study included 85 arsenic-exposed male workers and 85 controls. Urinary arsenic was measured as an exposure biomarker. Thyroid hormones and endothelial biomarkers were analyzed. Correlation and multivariable regression analyses were performed. Exposed workers had lower triiodothyronine and thyroxine levels and higher thyroid-stimulating hormone levels (all P < 0.001). ADMA and SDMA concentrations were significantly elevated. Urinary arsenic correlated with endocrine and endothelial biomarkers and independently predicted ADMA (β = 0.009) and SDMA (β = 0.003) (both P < 0.001). Chronic occupational arsenic exposure is associated with concurrent endocrine and endothelial alterations, supporting integrated biomarker-based surveillance in occupational health.

Urinary arsenic speciation, methylation capacity, and growth outcomes in longitudinal mother-child pairs across pregnancy to preschool age: A single prenatal spot measurement poorly predicts children's arsenic profiles and growth.

This study was conducted to identify the association between arsenic exposure and stunting in children under 5 years of age and to identify its effect on their cognitive function. The current study was a prospective case control study conducted in the Outpatient Nutrition Clinic at the Assiut University Children's Hospital for a 6-month period. The weight and height of children were measured to determine nutritional status using the weight-for-age Z-score (WAZ) or height-for-age Z-score (HAZ) using the WHO Anthro software. Children who were diagnosed with moderate and severe stunting were compared with an age- and sex-matched control group. Dietary profiles and cognitive functions were assessed using questionnaires that were translated from the original language (English) into the target language (Arabic). Hair samples were collected for the detection of arsenic level among the selected stunted children and their corresponding control group. 56.7% of the examined children were diagnosed as stunted cases. Statistically significant high arsenic levels in hair were found among the stunted children compared with the controls. The median arsenic level was 0.083 mg/kg in stunted cases while in controls, it was 0.042. It was found that 43.4% of stunted children had high arsenic levels in their hair, 50% of them were in the age group (25-36 months), 55% of them were female, and 75.0% of the children's families were residing in rural areas; these differences were statistically insignificant. Delayed development in communication, problem-solving, and personal-social domains was higher in children with high arsenic levels compared to children with low arsenic levels but was not statistically significant. A significantly positive weak correlation was found between arsenic level in hair and frequency of artificial snacks consumption. As a conclusion, stunting was diagnosed in 56.7% of the study sample and was associated with high arsenic level in the hair samples of the affected children.

Long-term groundwater arsenic exposure is associated with altered arsenic methylation capacity and gut microbiota composition in a rural Chinese population.

The key regulator circ_0003295 promotes arsenic-induced lung carcinogenesis and progression by enhancing mitochondrial function.

Environmental Heavy Metal Pollution Disrupts Heading in Major Cereal Crops: Mechanisms and Implications for Food Security.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden and major contributor to chronic liver disease. Evidence suggests arsenic (As) and/or cadmium (Cd) exposure may influence MASLD development, yet effects of chronic low-dose metal mixtures on hepatic inflammation and immune responses remain unclear. Using the apolipoprotein E-knockout mouse model, we examined low-dose As and Cd exposure in male and female mice. We focused on hepatic steatosis and inflammation. Steatosis-related changes were assessed via lipid metabolism gene expression and PLIN2 levels. No significant changes were observed in males; however, females exposed to the metal mixture showed increased PLIN2 expression. In contrast, males exhibited an inflammatory phenotype following combined exposure. High-plex single-cell imaging (PhenoCycler) in male livers revealed increased Ki67+ hepatocytes, enhanced β-catenin signal, and elevated CD8+ T-cell infiltration, indicating enhanced proliferation and immune activation. These findings suggest sex-dependent responses to low-dose As and Cd, with females showing subtle steatotic changes and males a pronounced inflammatory signature. Collectively, combined metal exposure induces hepatic priming in both sexes; males show an increased inflammatory response with cellular proliferation in the absence of overt steatosis or fibrosis, whereas females demonstrate increased steatosis without inflammation or fibrosis.

Impact of low levels of arsenic in drinking water with incident urologic cancers in Washington state.

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults and is closely linked to dysfunction of the retinal pigment epithelium (RPE). Arsenic (As), a ubiquitous environmental toxicant present in drinking water and food, has been implicated in multiple chronic diseases. However, its role in AMD remains unclear. This study aimed to investigate the effects of As exposure on AMD-related retinal injury and to elucidate the underlying molecular mechanisms using in vitro and in vivo experimental models. ARPE-19 cells were treated with sodium iodate (NaIO3) to establish an AMD-like injury model and then exposed to 1 µM As to assess cell viability, apoptosis, oxidative stress, mitochondrial dysfunction, autophagy-related changes and epithelial barrier integrity. Evaluation of NF-κB signaling pathway activation using molecular biology techniques. In vivo, a NaIO3-induced mouse model of AMD was established and combined with As exposure at 25 ppm to to validate retinal damage, oxidative stress, mitochondrial impairment, and barrier dysfunction. ShRNA-mediated silencing of NF-κB was further used to confirm pathway involvement. As exposure significantly aggravated NaIO3-induced injury in ARPE-19 cells and mouse retinas. In vitro, As reduced cell viability and enhanced apoptosis, inflammatory responses, reactive oxygen species accumulation, mitochondrial dysfunction, autophagy dysregulation, and epithelial barrier disruption. In vivo, As exacerbated retinal structural damage, increased oxidative stress, impaired mitochondrial function, and further reduced the expression of tight junction proteins in NaIO3-treated mice. Mechanistically, these effects were accompanied by sustained activation of the NF-κB signaling pathway. ShRNA-mediated silencing of NF-κB partially reversed As-induced retinal damage in vivo. Our study found that As exposure exacerbated AMD-like retinal degeneration via NF-κB pathway. These findings identified As as a potentially modifiable environmental risk factor for AMD and suggested that individuals in As-endemic regions may benefit from targeted retinal screening. Moreover, NF-κB pathway targets inhibition emerged as a candidate strategy for mitigating As-exacerbated retinal injury.

Liver fibrosis is a reversible phase of arsenic-induced chronic liver injury, with bile acid metabolic alterations closely associated with this pathological process. SIRT1 is a key metabolic regulator and promising therapeutic candidate, while its role in bile acid metabolism during arsenic-induced liver fibrosis remains poorly defined. This study established time-dependent rat models of arsenic-induced liver fibrosis with resveratrol intervention to investigate the potential association between SIRT1, bile acid metabolic disturbance, and liver fibrosis, as well as resveratrol’s hepatoprotective effects. Arsenic exposure induces progressive accumulation of hydrophobic bile acids in the liver, inflammation, hepatic stellate cell activation, and fibrosis, accompanied by suppressed expression of bile acid phase II detoxification genes (Baat, Ugt1a1, Sult2a1) and the bile acid efflux transporter gene Abcb11 (BSEP). Arsenic exposure reduces SIRT1 expression and increases C/EBPα acetylation, which may relate to impaired transcription of the aforementioned bile acid metabolic genes. Resveratrol may restore SIRT1 expression, normalize C/EBPα acetylation and bile acid homeostasis, and reduce hepatic arsenic accumulation, thereby alleviating liver fibrosis. Collectively, the SIRT1/C/EBPα axis and bile acid metabolism may be linked to the progression of arsenic-induced liver fibrosis. Resveratrol may exert protective effects via multiple mechanisms, including regulating these molecular targets and reducing hepatic arsenic accumulation.

Arsenic, a toxic metalloid widespread in groundwater, induces multi-organ damage upon chronic exposure. The male reproductive system, which is crucial for species propagation, requires a stable testicular microenvironment to function properly. Although the reproductive system is recognized as one of the most sensitive targets of arsenic toxicity, the underlying molecular mechanisms and effective intervention strategies remain incompletely understood. In this study, we systematically evaluated the impact of chronic arsenic exposure on testicular function in male C57BL/6J mice administered sodium arsenite (NaAsO₂) in their drinking water for six months. Our results found that chronic arsenic exposure decreased sperm quality, induced testicular oxidative stress and inflammation, and caused the blood-testicular barrier(BTB) injury in mice. Meanwhile, chronic arsenic exposure increased the Fe²⁺ content and the levels of ferroptosis-related mRNA/protein, and decreased the mRNA/protein levels of Nrf2/GPX4 signaling pathway in the testis. Notably, supplementation with Xylo-oligosaccharides (XOS) derived from Miscanthus lutarioriparius effectively alleviated the arsenic-induced decline in sperm quality, testicular damage, oxidative stress and inflammation. Further mechanistic investigation revealed that XOS exerts its protective effects by activating the Nrf2/GPX4 signaling pathway in the testes, thereby inhibiting the ferroptosis process. Overall, our findings provide a potential preventive strategy against arsenic-induced male reproductive injury.

MiR-124-3p-regulated HMGB1 is involved in arsenic-induced renal fibrosis through promoting secretion of inflammatory factors in renal tubular epithelial cells.

Maternal and early-life arsenic exposure and relative telomere length in children: Findings from the BiRCH cohort.

Folate is an essential nutrient that supports the formation of S-adenosyl methionine (SAM) in the pathway of one carbon metabolism. Dietary folate intake has been shown to affect the SAM-dependent methylation of diverse substrates, including DNA and inorganic arsenic (iAs). The methylation of iAs by arsenic methyltransferase (AS3MT) plays a key role iAs detoxification in both humans and mice. Our recent studies using wild-type C57BL/6N mice showed that preconception exposure to iAs resulted in heritable changes in DNA methylation in paternal sperm and differential expression of genes in tissues of the offspring that developed a diabetic phenotype. The goal of the present study was to determine if dietary folate can modify the iAs-induced differential methylation of DNA in sperm of male C57BL/6 mice expressing the human AS3MT and exhibiting a human-like pattern of iAs metabolism. Mice were fed folate deficient (FD, 0mg folic acid/kg) or folate supplemented (FS, 10mg folic acid/kg) diet for 6 weeks, followed by exposure to 0 (controls) or 400 ppb iAs (arsenite) in drinking water for 5 weeks while on the same types of diet. Reduced Representation Bisulfite Sequencing was used to identify CpG sites and genes that were differentially methylated in response to iAs exposure, followed by analysis of pathways enriched for these genes. Genes and pathways associated with cell morphology and function, and neural structure and function were the top pathways enriched by iAs exposure in both FD and FS mice. Notably, pathways associated with diabetes, regulation of insulin secretion and signaling were enriched for differentially methylated genes only in the sperm of iAs-exposed FS mice. These results suggest that folate intake modifies the effects of iAs exposure on DNA methylation in sperm of the humanized mice, providing strong rationale for studies that will examine the role of folate in modulation of adverse effects of preconception exposure to iAs.

Arsenic poisoning significantly elevates the risk of cancer and other chronic illnesses. The goal of this research is to identify important genes whose expression changes in response to arsenic toxicity, and the molecular pathways affected by arsenic, using computational analysis of arsenic toxicity profiles. This approach will computationally identify and analyze genes whose expression changes in response to arsenic, thereby elucidating the heightened risk of carcinogenesis in arsenic-exposed individuals. This work employed high-throughput arsenic toxicity profiles to computationally identify and analyze expressed genes (DEGs) differentially in Affymetrix microarray datasets from the Gene Expression Omnibus (GEO) database, which were screened using the GEO2R program. A protein-protein interaction (PPI) network was constructed using STRING to elucidate the functional links between these DEGs and DNA repair genes. Interactions between the seven central genes (E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS) and the repair genes PARP1, NBN, PMS1, MSH3, XRCC5, XRCC6, MGMT, and MLH1 were discovered. We employed the DAVID and Enrichr-KG platforms to investigate the functions of these genes and their associations with cellular and molecular processes in greater detail. Two hundred eighty-one non-synonymous single-nucleotide polymorphisms (nsSNPs) in the 07 genes linked to arsenic toxicity were found using the COSMIC database. Based on our analysis, mutations in E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS can hinder DNA repair mechanisms, ultimately leading to cancer. Our computational analysis demonstrated that these non-synonymous SNPs can affect gene function, potentially altering protein stability and activity. Furthermore, according to Metal-Protein docking and protein-protein docking, these genes and their mutations appear to affect interactions with repair proteins substantially. Specific dietary consumption may lessen the detrimental effects of arsenic poisoning on protein function. We hypothesized that the mutations might be reversed by attaching particular molecules to these mutants. The protective effects of six curcumin compounds were examined using molecular docking with AutoDock 4.2.6 to assess protein dynamics and binding interactions. Optimal complexes were selected for dynamics simulation using GROMACS, and potential strategies for long-term cancer prevention related to arsenic exposure were identified.