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Arsenic, a toxicant widely distributed in the environment, is considered as a risk factor for liver fibrosis. At present, the underlying mechanism still needs to be explored. In the present study, we found that, for mice, chronic exposure to arsenic induced liver fibrosis, activated the NLRP3 inflammasome, and increased the levels of reactive oxygen species (ROS). After hepatocytes were co-cultured with hepatic stellate cells (HSCs), we observed the arsenic-activated NLRP3 inflammasome in hepatocytes, and the co-cultured HSCs were activated. Further, we found that, in livers of mice, arsenic disturbed GSH metabolism and promoted protein S-glutathionylation. A 3D molecular docking simulation suggested that NLRP3 binds with GSH, which was confirmed by immunoprecipitation experiments. N-acetylcysteine (NAC) increased the levels of GSH in hepatocytes, which suppressed the S-glutathionylation of NLRP3 and blocked arsenic-induced activation of the NLRP3 inflammasome. Mechanistically, an imbalance of the redox state induced by arsenic promotes the S-glutathionylation of NLRP3, which regulates activation of the NLRP3 inflammasome, leading into the activation of HSCs. Moreover, NAC increases the levels of GSH to block arsenic-induced S-glutathionylation of NLRP3, thereby blocking arsenic-induced liver fibrosis. Thus, via activating HSCs, the S-glutathionylation of NLRP3 in hepatocytes is involved in arsenic-induced liver fibrosis, and, for hepatocytes, NAC alleviates these effects by increasing the levels of GSH. These results reveal a new mechanism and provide a possible therapeutic target for the liver fibrosis induced by environmental factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO 2 ) and 10 mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO 2 -induced liver injury. The findings suggested that prolonged exposure to NaAsO 2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO 2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO 2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to arsenic during gestation has lasting health-related effects on the developing fetus, including an increase in the risk of metabolic disease later in life. Epigenetics is a potential mechanism involved in this process. Ten-eleven translocation 2 (TET2) has been widely considered as a transferase of 5-hydroxymethylcytosine (5hmC). Here, mice were exposed, via drinking water, to arsenic or arsenic combined with ascorbic acid (AA) during gestation. For adult offspring, intrauterine arsenic exposure exhibited disorders of glucose metabolism, which are associated with DNA hydroxymethylation reprogramming of hepatic nuclear factor 4 alpha (HNF4α). Further molecular structure analysis, by SEC-UV-DAD, SEC-ICP-MS, verified that arsenic binds to the cysteine domain of TET2. Mechanistically, arsenic reduces the stability of TET2 by binding to it, resulting in the decrease of 5hmC levels in Hnf4α and subsequently inhibiting its expression. This leads to the disorders of expression of its downstream key glucose metabolism genes. Supplementation with AA blocked the reduction of TET2 and normalized the 5hmC levels of Hnf4α, thus alleviating the glucose metabolism disorders. Our study provides targets and methods for the prevention of offspring glucose metabolism abnormalities caused by intrauterine arsenic exposure., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arsenic is a well-known environmental toxicant and emerging evidence suggests that arsenic exposure has potential skeletal muscle toxicity; however, the underlying mechanism has not yet been clarified. The aim of this study was to investigate the correlation among adverse effects of subchronic and chronic environmental arsenic exposure on skeletal muscle as well as specific myokines secretion and angiotensin II (AngII)-melatonin (MT) axis in rats. Four-week-old rats were exposed to arsenite (iAs) in drinking water at environmental relevant concentration of 10 ppm for 3 or 9 months. Results indicated that the gastrocnemius muscle had atrophied and its mass was decreased in rats exposed to arsenite for 9 months, whereas, they had no significant changes in rats exposed to arsenite for 3 months. The levels of serum-specific myokine irisin and gastrocnemius muscle insulin-like growth factor-1 (IGF-1) were increased in 3-month exposure group and decreased in 9-month exposure group, while serum myostatin (MSTN) was increased significantly in 9-month exposure group. In addition, serum AngII level increased both in 3- and 9-month exposure groups, while serum MT level increased in 3-month exposure group and decreased in 9-month exposure group. Importantly, the ratio of AngII to MT level in serum increased gradually with the prolongation of arsenite exposure. It showed a certain correlation between AngII-MT axis and gastrocnemius muscle mass, gastrocnemius muscle level of IGF-1 or serum levels of irisin and MSTN. In conclusion, the disruption of AngII-MT axis balance may be a significant factor for skeletal muscle atrophy induced by chronic environmental arsenic exposure., (© 2023 Wiley Periodicals LLC.)

The environmental toxicant arsenic causes various human diseases and threatens millions of people worldwide. Recently, a limited number of studies have revealed that exposure to arsenic is associated with thyroid dysfunction, indicating its toxicological impact on the thyroid gland, however, its precise forms of damage and underlying mechanisms remain largely unknown. Here, we sought to observe the thyrotoxicity of sodium arsenite (NaAsO 2 ) on human thyroid follicular epithelial cells (Nthy-ori 3-1) and SD rats, and explore the role of Bax/Bcl-2 ratio in the above process. Our results displayed that NaAsO 2 exerted a dose-dependent inhibitory effect on the viability of Nthy-ori 3-1 cells. Alongside the increase doses of NaAsO 2 exposure, morphological changes and elevated LDH levels were observed. Furthermore, apoptosis rates increased in a dose- and time-dependent manner, accompanied by a decrease in Bcl-2 and an opposite change in Bax expression. SD rats were treated with 0, 2.5, 5, and 10 mg/kg NaAsO 2 for 36 weeks. Our findings revealed that NaAsO 2 exposure resulted in arsenic accumulation in thyroid tissue, elevated ratio of Bax/Bcl-2, and histopathological changes of thyroid in rats, which accompanied by the decreased serum T 3 and T 4 levels and the increased serum TSH level. Furthermore, T 3 and T 4 levels were negatively correlated with Bax expression, whereas positively correlated with Bcl-2 expression. Collectively, our results suggest that NaAsO 2 exposure induces cytotoxicity in Nthy-ori 3-1 cells, causes structural damages and dysfunction of thyroid in SD rats, in which the imbalance of Bax/Bcl-2 ratio may play a significant role., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic, a common environmental hazard, is a risk factor for nonalcoholic fatty liver disease (NAFLD). However, the mechanism remains unclear. Here, we found that chronic exposure to environmental-related doses of arsenic disturbed fatty acid and methionine metabolism in mice, caused liver steatosis, increased arsenic (3) methyltransferase (As3MT), sterol regulatory element binding protein 1 (SREBP1) and lipogenic gene levels, and decreased N6-methyladenosine (m 6 A) and S-adenosylmethionine (SAM) levels. Mechanistically, arsenic blocks m 6 A-mediated miR-142-5p maturation by consuming SAM via As3MT. miR-142-5p was involved in arsenic-induced cellular lipid accumulation by targeting SREBP1. SAM supplementation or As3MT deficiency blocked arsenic-induced lipid accumulation by promoting the maturation of miR-142-5p. Moreover, in mice, folic acid (FA) and vitamin B12 (VB 12 ) supplementation blocked arsenic-induced lipid accumulation by restoring SAM levels. Arsenic-exposed heterozygous As3MT mice showed low liver lipid accumulation. Our study demonstrates that SAM consumption caused by arsenic, through As3MT, blocks m 6 A-mediated miR-142-5p maturation, thereby elevating the levels of SREBP1 and lipogenic genes, leading to NAFLD, which provides a new mechanism and biological insights into the therapy of NAFLD induced by environmental factors., Competing Interests: Declaration of competing interest The authors declare they have no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Arsenic is a well known environmental hazardous material, chronic arsenic exposure results in different types of liver damage. Among them, liver fibrosis has become a research hotspot because of its reversibility, while the underlying mechanism is still unclear. Previous studies revealed that EGFR/ERK signaling appears to play an important role in fibrosis diseases. In this study, sprague-dawley rats were exposed to different doses of arsenite for 36 weeks to investigate the roles of EGFR/ERK signaling on arsenite-induced liver fibrogenesis. Our results showed that long-term arsenite exposure induced liver fibrosis, accompanied by hepatic stellate cells (HSCs) activation, excessive serum secretion of extracellular matrix (ECM), and hepatocytes epithelial-mesenchymal transformation (EMT). In addition, arsenite exposure caused hyperphosphorylation of EGFR/ERK signaling in liver tissue of rats, indicating that EGFR/ERK signaling may be involved in arsenite-induced liver fibrosis. Indeed, erlotinib (a specific phosphorylation inhibitor of EGFR) intervention significantly decreased arsenite induced hyperphosphorylation of EGFR/ERK signaling, thereby suppressed hepatocytes EMT process and alleviated liver fibrogenesis in arsenite exposed rats. In summary, the present study provides evidences showing that hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes EMT and liver fibrosis in rats, which brings new insights into the pathogenesis of arsenic-induced liver injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic is a widespread naturally contaminant. Previous studies have highlighted the issue of liver fibrosis induced by arsenic exposure, while the exact mechanisms are not yet fully understood. Recent studies suggest that Mig-6/EGFR/ERK signaling appear to play important roles in fibrosis caused by various factors. In this study, we focused on the epigenetic modification combined with the signaling dysregulation to validate the role of Mig-6 in regulating EGFR/ERK signaling in arsenite-induced human hepatic stellate cells (HSCs) activation. Our results revealed that arsenite exposure induced HSCs activation and extracellular matrix (ECM) deposition. The EGFR/ERK signaling was significantly hyperphosphorylated in arsenite-exposed HSCs, and Mig-6 inactivation was involved in arsenite induced hyperphosphorylation of EGFR and activation of HSCs. Additionally, we further illustrated that hypermethylation of Mig-6 gene promoter region was responsible for the downregulation of Mig-6 induced by arsenite exposure. Moreover, 5-Aza-dC (a DNA methyltransferase inhibitor) can efficiently rescue hypermethylation of Mig-6 gene, decrease the hyperphosphorylation of EGFR/ERK signaling, then reverse arsenite induced HSCs activation. Taken together, the present study strongly suggests that inactivating of Mig-6 function by hypermethylation of its promoter region leading to hyperphosphorylation of EGFR/ERK signaling, and is involved in arsenite-induced HSCs activation and ECM deposition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

As an environmental toxicant, arsenic causes damage to various organs and systems of the body and has attracted worldwide attention. It is well-known that exposure to arsenic can induce pulmonary fibrosis, but the molecular mechanisms are elusive. Glycolysis is involved in the process of various diseases, including pulmonary fibrosis. Extracellular vehicles (EVs) are mediators of cell communication through transporting miRNAs. The potential of miRNAs in EVs as liquid biopsy biomarkers for various diseases has been reported, and they have been applied in clinical diagnoses. In the present investigation, we focused on the roles and mechanisms of miR-21 in EVs on arsenic-induced glycolysis and pulmonary fibrosis through experiments with human populations, experimental animals, and cells. The results for arsenicosis populations showed that the serum levels of hydroxyproline, lactate, and EVs-miRNAs were elevated and that EVs-miR-21 levels were positively related to the levels of hydroxyproline and lactate. For mice, chronic exposure to arsenite led to high levels of miR-21, AKT activation, elevated glycolysis, and pulmonary fibrosis; however, these effects were blocked by the depletion of miR-21 in miR-21 knockout (miR-21 KO ) mice. After MRC-5 cells were co-cultured with arsenite-treated HBE cells, the levels of miR-21, AKT activation, glycolysis, and myofibroblast differentiation were enhanced, effects that were blocked by reducing miR-21 and by inhibiting the EVs in HBE cells. The down-regulation of PTEN in MRC-5 cells and primary lung fibroblasts (PLFs) reversed the blocking effect of inhibiting miR-21 in HBE cells. Thus, miR-21 down-regulates PTEN and promotes glycolysis via activating AKT, which is associated with arsenite-induced myofibroblast differentiation and pulmonary fibrosis. Our results provide a new approach for the construction of clinical diagnosis technology based on analysis of the mechanism of arsenite-induced pulmonary fibrosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Arsenic is a well-known environmental toxicant and carcinogen, which has been epidemiologically proved related to the increased hepatic disorders. Researches have shown that aseptic inflammation and abnormal immune response are associated with arsenic-induced liver injury. However, the immunotoxic effects of liver have not been extensively characterized. Ginkgo biloba extract (GBE), a natural products of G. biloba leaves with proven anti-inflammatory and potential immunoregulatory activities, was used as intervention agent to explore its protective effects on arsenic-induced hepatotoxicity. Thus, the underlying mechanism of the immunotoxic effects on arsenic-induced liver injury were investigated in 2.5, 5.0, and 10.0 mg/kg NaAsO 2 of Wistar rats for 16 weeks. Subsequently, GBE was used as intervention agent in 50 mg/kg for 6 weeks after cessation of arsenic exposure. The ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver were detected. Meanwhile, the notable activation of aseptic inflammation-related molecule TLR4 and its downstream targets MyD88 and NF-κB in the liver were observed. In this work, we confirmed that subchronic exposed to arsenic triggered the infiltration of inflammatory cells in rat liver, coupled with obvious histopathological changes and aberrant hepatic serum biochemical parameters. Meanwhile, imbalanced immune response was verified by the notable abnormal ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver of arsenic exposed rats. Further, the level of TLR4, MyD88, and NF-κB in liver both transcription and translation activity were raised. Subsequently, GBE markedly mitigated arsenic-induced liver injury, most impressively, post treatment with GBE prominently suppressed the overactivated inflammatory-related TLR4-MyD88-NF-κB pathway and evidently decreased the secretion of inflammation cytokines. Meanwhile, the disturbance of pro- and anti-inflammatory response was reversed. We concluded that the disruption of pro- and anti-inflammatory T-cells balance caused by cytokines mediated cell-cell interactions may be one of the mechanisms underlying arsenic-induced liver injury and that GBE intervention exerts an evidence protective effects, which might be closely associated with the suppression of inflammatory-related TLR4 pathway., (© 2021 Wiley Periodicals LLC.)

Arsenic is a naturally occurring environmental toxicant, chronic exposure to arsenic can cause multiorgan damage, except for typical skin lesions, liver damage is the main problem for health concern in population with arsenic poisoning. Abnormal apoptosis is closely related to liver-related diseases, and p53 is one of the important hallmark proteins in apoptosis progression. This study was to investigate whether arsenic poisoning-induced hepatocyte apoptosis and the underlying role of p53 signaling pathway. A rat model of arsenic poisoning was established by feeding corn powder for 90 days, which was baked with high arsenic coal, then were treated with Ginkgo biloba extract (GBE) for 45 days by gavage. The results showed that arsenic induced liver damage, increased hepatocyte apoptosis and elevated the expression level of Chk1 and the ratios of p-p53/p53 and Bax/Bcl-2 in liver tissues, which were significantly attenuated by GBE. Additionally, to further demonstrate the potential apoptosis-associated mechanism, L-02 cells were pre-incubated with p53 inhibitor pifithrin-α (PFTα), ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor (CGK733) or GBE, then treated with sodium arsenite (NaAsO 2 ) for 24 h. The results showed that GBE, PFTα or CGK733 significantly reduced arsenic-induced Chk1 expression and the ratios of p-p53/p53 and Bax/Bcl-2. In conclusion, Chk1-p53 pathway was involved in arsenic poisoning-induced hepatotoxicity, and inhibiting of Chk1-p53 pathway ameliorated hepatocyte apoptosis caused by coal-burning arsenic poisoning. The study provides a pivotal clue for understanding of the mechanism of arsenic poisoning-induced liver damage, and possible intervention strategies.

Background: Currently, most arsenic (As) studies in populations are concerned with water-borne arsenicosis. However, residents in Xingren County of Guizhou Province, Southwest of China, represent a unique case of arsenicosis which is related to indoor combustion of high As-containing coal. This study aimed to assess the alterations of As levels and its risk factors in coal-borne arsenicosis residents during the past 20 years., Methods: Four follow-up investigations in Xingren County were selected from the year 1998 to 2017, a total of 245, 272, 584, and 309 residents were involved in the four investigations, respectively. Local external environmental medium (coal, soil, water, air, rice, corn and chili peppers) and biological samples (urine, hair) were collected at each time of investigation for total As analysis. Sociodemographics and lifestyles variables were extracted from the questionnaire investigation. Both univariate and multivariate unconditional logistic regression models were performed to analyze the variation of risk factors for coal-borne arsenicosis., Results: A substantial reduction of total As levels was observed both in external environmental medium and biological samples in the unique coal-borne arsenicosis region, especially since the year 2006. In addition, age, duration of consuming high As-containing coal and smoking status were found to be the most significant risk factors for coal-borne arsenicosis during the past 20 years by both two different logistic regression models. Room ventilation and grain drying modes were no longer to be risk factors since 1998 survey. Annual household income had always been an important protective factor for coal-borne arsenicosis in recent 20 years by both two different logistic regression models. Grain storage modes had become significant protective factor in 2014 and 2017 survey. A certain correlation between sex, education and coal-borne arsenicosis was observed by univariate logistic regression model but no clear links were found by multivariate logistic regression model., Conclusions: Considerable efforts to blocking As exposure from burning coal and As contaminated foods in this region are observed over the study period. Further practical health education programs may need to target individuals with long-term of As exposure, lower socioeconomic status and smoking in order to better prevent and control the occurrence and development of coal-borne arsenicosis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Algal blooms decay affects the mobility, bioavailability, and toxicity of arsenic (As) in aquatic environments. The decaying process alters aquatic redox conditions and also introduces ample organic matter, conditions favorable for microbial reduction to simulate As release and As species transformation. This study investigated the role of algae (Microcystis aeruginosa (MA)) blooms decay on the dynamics of labile As and elements associated with its release, such as iron (Fe), manganese (Mn) and sulfide (S), at the sediment-water surface (SWI) of a shallow lake (Lake Taihu) in China, applying mesocosm incubation. A combined AgI/ZrO-Chelex diffusive gradients in thin films (DGT) technology was used to examine labile As, Fe, Mn, and S variations in sediments during none-MA, low-MA, and high-MA treatments. High-MA blooms decay generated strong anoxic conditions, which are favorable for the release of labile As, Fe, Mn, and S from sediment. Labile S produced from the reduction of sulfate caused by decaying MA was likely removed by labile Fe through the formation of Fe-sulfides under reducing conditions. Furthermore, this condition facilitated arsenate (As(V)) reduction to arsenite (As(III)), which was weakly adsorbed by Fe-sulfides and thus mobilized to the aqueous phase. An increase in the sediment resupply of solids As to pore water along with MA blooms decay was also revealed by the DGT-induced fluxes in sediment model, coupled with the average desorption rate constant increasing from 0.27 × 10 -6  s -1 to 3.41 × 10 -6  s -1 , and the average response time decreasing from 7859 s to 1538 s., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: It is generally acknowledged that the determination of harmful chemical compounds excreted into saliva is useful for assessing their exposure levels. The aim of the present study was to compare the total arsenic and its species in saliva and urine samples collected from the people residing in an arsenic-contaminated area of China and to further verify the feasibility of using salivary arsenic as a new biomarker of arsenic exposure., Methods: Total arsenic and speciation analyses in urine and saliva samples among 70 residents exposed to arsenic from drinking water in Shanxi, China were carried out by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP/MS)., Results: The result showed that, total arsenic concentration in saliva was relatively lower than in urine samples, but it existed a strong positive correlation with total urinary arsenic, drinking water arsenic and different skin lesions. For arsenic metabolism analyses, As III , As V , MMA, and DMA were detected in all of the urine samples with the dominating species of DMA (73.2%). Different with urinary arsenic species, most arsenic species in saliva were not methylated. The major species in saliva was iAs (As III  + As V , 76.18%), followed by DMA (13.08%) and MMA (9.13%). And the primary methylation index (PMI), second methylation index (SMI) and proportion of the four different species (As III , As V , MMA, and DMA) in saliva showed no significant positive relationship with that of in urine., Conclusions: These findings indicated saliva may be used as a useful tool for biological monitoring of total arsenic exposure in the crowd rather than an efficient tool for assessing arsenic metabolism in human body after exposed to arsenic.

Spatial and seasonal variations of arsenic species in Lake Taihu (including Zhushan Bay, Meiliang Bay, Gonghu Bay, and Southern Taihu) were investigated. Relatively high levels of total arsenic (TAs) and arsenate (As(V)) were observed in hyper-eutrophic regions during summer and autumn, which is attributed to exogenous contamination and seasonal endogenous release from sediments. The distributions of TAs and As(V) were significantly affected by total phosphorus, iron, manganese, and dissolved organic carbon. Arsenite (As(III)) and methylarsenicals (the sum of monomethylarsenic acid (MMA(V)) and dimethylarsenic acid (DMA(V))), mainly from biotransformation of As(V), were affected by temperature-controlled microalgae activities and local water quality parameters, exhibiting significantly higher concentrations and proportions in hyper-eutrophic and middle eutrophic regions during summer compared to mesotrophic region. The eutrophic environment, which induces changes in the main water quality parameters such as phosphorus, chlorophyll-a, iron, manganese, and dissolved organic carbon, can favor the biogeochemical cycling of arsenic in the aquatic systems., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To investigate the level of ROS, MDA and SOD in different stages of arsenic-induced neoplastic transformation in human keratinocytes., Methods: HaCaT human immortalized keratinocytes were continuously exposed to 1.0 μmol/L arsenite for 35 passages. The secretion of active MMP-9, the proliferation rate and doubling time nd colony formation assay in soft agar colony were used to identify the malignant phenotype of the arsenite-exposed HaCaT cells. Then flow cytometry was used to detect the levels of ROS, and the level of MDA and SOD were tested by biochemical method at different passages of arsenite exposure in HaCaT cells., Results: A marked increase in the secretion of active MMP-9 in the arsenic-treated (1.0 μmol/L NaAsO2) cells was observed in comparison to the passage-matched untreated control (0.0 μmol/L NaAsO2) cells at 28 and 35 passages. And compared with 0.0 μmol/L NaAsO2 group, the proliferation rate and doubling time in 1.0 μmol/L NaAsO2 group was much faster at 21 ((64.37 ± 15.92) h) and 28 ((64.04 ± 12.84) h) passages with a significant statistical difference at passage 35 ((54.00 ± 2.35 ) h) (P < 0.05). Furthermore, the long-term arsenite-treated cells formed significantly higher colonies (107 ± 11 in passage 35) in soft agar than control cells (P < 0.05). No obvious regularity changes of ROS and MDA levels were found before 14 passages of arsenite exposure, except for passage 1. Surprisingly, after 14 passages, with the increased passages of exposure to arsenite, both the ROS and MDA levels decreased gradually, the ROS level at passage 35 was significant lower compared to passage 0 (P < 0.05). Conversely, after passage 21, the activity of SOD was obviously enhanced and reached the highest level at passage 35., Conclusion: Long-term exposure to low concentrations of inorganic arsenic-induced malignant transformation of HaCaT cells is accompanied by intracellular imbalance between oxidative-antioxidant, which increased expression of SOD and low levels of ROS found in the later-stage of arsenite-induced transformation.

Objective: To compare the total arsenic concentration between blood and saliva after oral administration of sodium arsenite to SD rats., Methods: A single oral gavage dose of sodium arsenite (20mg/kg) was administrated to 21 adult male Sprague-Dawley rats. Then collected blood and saliva samples at 0, 1-2, 4-5, 7-8, 11-12, 17-18, 23-24 hour for total arsenic detection. The blood samples were detected for total arsenic concentration by Atomic Fluorescence Spectrometry (AFS-230) and the salivary arsenic were detected by inductively coupled plasma mass spectrometry (ICP-MS)., Results: After intake of 20 mg/kg BW sodium arsenite, the total arsenic concentration in blood of SD rats was increased rapidly, and reached the peak value at the 1-2 hour, then descended gradually. However, there was a second peak value at the 7-8 hour. The upward trend of salivary arsenic was more slowly than blood arsenic, and reached the peak value at the 7-8 hour, then descended gradually. The variation tendency of salivary arsenic and blood arsenic with time were basically the same. Besides, there was an obvious positive association between them, the correlation coefficient was 0.678, P < 0.01., Conclusion: The excretion of arsenic in saliva was slower than that of blood samples after administrated a single oral gavage dose of sodium arsenite (20 mg/kg) to SD rate, but the metabolism mode of arsenic in saliva was similar with that in blood, suggested that salivary arsenic can also well reflect the exposure level of arsenic in the body.

Arsenic is a kind of widespread environmental toxicant with multiorgan-toxic effects, and arsenic exposure is associated with the occurrence and development of many chronic diseases. The influence of environmental arsenic exposure on skeletal muscle, which is a vital organ of energy and glucose metabolism, has received increasing attention. This study aimed to investigate the types of inorganic arsenic-induced skeletal muscle injury, and the potential regulatory effects of melatonin (MT) and erythropoietin (EPO) in young (3-month-old) and middle-aged (12-month-old) rats. Our results showed that 1 mg/L sodium arsenite exposure for 3 months could accelerate gastrocnemius muscle atrophy and promote the switch of type II fibers to type I fibers in middle-aged rats; however, it did not cause significant pathological changes of gastrocnemius muscle in young rats. In addition, arsenite could inhibit serum MT levels, and promote serum EPO levels but inhibit EPO receptor (EPOR) expression in gastrocnemius muscle in middle-aged rats, while serum MT levels and EPOR expression in gastrocnemius muscle showed an opposite effect in young rats. Importantly, exogenous MT antagonized the arsenite-induced skeletal muscle toxic effect and restored serum EPO and gastrocnemius muscle EPOR expression levels in middle-aged rats. There was a positive correlation among gastrocnemius muscle index, serum MT level, and gastrocnemius muscle EPOR protein level in arsenite-exposed rats. This study demonstrated that inorganic arsenic could accelerate skeletal muscle mass loss and type II fiber reduction in middle-aged rats, which may be related to decreased MT secretion and declined EPO sensitivity in skeletal muscle. [ABSTRACT FROM AUTHOR]

There are no reports in scientific literature on arsenic species in human saliva after seaweed exposure. The present article reports for the first time the regular excretion patterns of arsenic in the saliva of volunteers with one-time ingestion of Chinese seaweed. Total arsenic and speciation analyses were carried out by high-performance liquid chromatography–inductively coupled plasma–mass spectrometry (HPLC-ICP-MS). Results show that the excretion time of total arsenic in saliva is a trifle earlier than that in urine, total arsenic in human saliva also shows a regular excretion pattern like that in urine within 72 h after exposure to seaweed. For speciation analysis, four species, including the major dimethylarsinic acid (DMA) species, were detected in urine prior to seaweed intake. Six species were detected in urine after seaweed ingestion, including DMA, methylarsonic acid (MMA), oxo-dimethylarsinoylethanol (oxo-DMAE), thio-dimethlyarsenoacetate (thio-DMAA), arsenite (AsIII) and arsenate (AsV). In saliva samples, three species were found before seaweed ingestion, with the major peak identified as AsIII. After consumption, the kinds of arsenic metabolites in saliva were less than those in urine. The major species was inorganic arsenic (iAs AsIII+AsV), followed by DMA, MMA and a trace amount of oxo-DMAE. Taken together, the present study suggests that saliva assay can be used as a potential tool for understanding the regular excretion pattern of total arsenic after seaweed ingestion. Whether or not it’s an efficient tool for assessing arsenic metabolites in humans exposed to seaweed requires further investigation. [ABSTRACT FROM PUBLISHER]

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial–mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions. [ABSTRACT FROM AUTHOR]