Research progress on the ferroptosis role in liver injury induced by inorganic arsenic / 中华地方病学杂志

Inorganic arsenic (iAs) is a common carcinogen that exists in the environment. Liver, as the main target organ of arsenic metabolism, long-term exposure to iAs can ultimately lead to carcinogenesis through two stages: liver fibrosis and cirrhosis. Ferroptosis is a type of programmed cell death caused by the accumulation of iron dependent lipid peroxides that affects the normal function of mitochondria. It has been found that ferroptosis occurs during liver fibrosis. Liver fibrosis caused by iAs has been a global health problem for a long time, but so far there is no effective treatment. The discovery of ferroptosis provides a new way to solve this problem. Therefore, this article will review the research progress of the mechanism of liver injury caused by iAs and ferroptosis.

Analyzing the difference between atomic fluorescence spectrometry and ICP-MS in the determination of arsenic in urine / 中国职业医学

@#Abstract: Objective （ ） To compare the measured results of arsenic in urine by atomic fluorescence spectrometry AFS and - （ - ）， Methods inductively coupled plasma mass spectroscopy ICP MS and analyze the reasons of the difference. The samples WS/T 474-2015 Determination of Arsenic in Urine by Hydride Generation Atomic Fluorescence were pretreated according to Spectrometry， （ ∶ ∶ ∶∶ ，V/V/V） and digested with mixed acid nitric acid sulfuric acid perchloric acid=3 1 1 and then determined by - - AFS and ICP MS. The samples were diluted with 0.50% nitric acid and determined by ICP MS. The samples included urine ， ， （ arsenic quality control samples inorganic arsenic supplemented samples and organic arsenic arsenic choline and arsenic ） - betaine supplemented samples. Standard curve method was used to compare the results of AFS method and ICP MS method. Results （ ） （ ） The results of quality control samples by AFS method digestion and ICP-MS method without digestion were ， - within the range of reference values but the values obtained by AFS method were lower than those obtained by ICP MS method. - - - ， The recovery of AFS and ICP MS was 97.79% 100.82% and 99.55% 99.98% respectively. In the middle and high ， - （ P ） concentration groups the measured values of inorganic arsenic by AFS were lower than that by ICP MS all <0.01 . The （ ） - recovery of arsenic betaine and arsenic choline by AFS method digestion was only 2.17% 2.63%. The values of arsenic betaine （ ） - （ and arsenic choline measured by AFS method digestion were lower than those measured by ICP MS method without ） - （ ）（ P ）Conclusion digestion and ICP MS method digestion all <0.01 . The result of urine arsenic measured by AFS method - ， was lower than that measured by ICP MS method which may be related to the mixed acid digestion of AFS method. Keywords: ； - ； ； ； ； ；

Analysis of arsenic speciation in Sepiae Endoconcha and research on its limit standard / 中国中药杂志

Sepiae Endoconcha is a common marine animal medicine,which generally contains high concentration of arsenic( As).The Chinese Pharmacopoeia( 2010 edition,part I) stipulated that the total As content of Sepiae Endoconcha should not exceed 2 mg·kg~(-1),while this limit was revised to 10 mg·kg~(-1) in the 2015 edition. So far,there is no research on the speciation of As in Sepiae Endoconcha,which made it hard to accurately evaluate its security risk. In this study,32 batches of Sepiae Endoconcha from different sources were collected. The safety risk assessment was carried out by determining the total As content and As speciation,inorganic As[As( Ⅲ),As( Ⅴ) ]and organic As( MMA,DMA,As C,As B) by HPLC-ICP-MS,and then the limit standard was discussed. The results showed that As B was the main form of As in Sepiae Endoconcha,followed by DMA and As( Ⅴ) ． Of the 32 batches of Sepiae Endoconcha,9 batches( accounting for 28%) were detected possessing i As. The maximum concentration of As( Ⅲ) was 103. 3 μg·kg~(-1),and the maximum concentration of As( Ⅴ) was 222. 4 μg·kg~(-1). According to the limit of i As in food,18. 75% of the samples exceeded the standard. The results indicate that there is no simple positive correlation between total As and As morphology in Sepiae Endoconcha. Besides,there is a risk in the total As limit,especially after the relaxation of the total As limit. The problem of high i As content caused by pollution and other factors is difficult to regulate. Since the toxicity of inorganic As is much higher than that of organic As,it is of great practical significance to establish inorganic As form limits in Sepiae Endoconcha.

Study on the disease burden of cancer attributed to the dietary inorganic arsenic exposure in Chinese population in 2013 / 中华预防医学杂志

Objective@#To estimate the burden attributed to the dietary inorganic arsenic exposure with lung cancer, bladder cancer and skin cancer as end points.@*Methods@#Inorganic arsenic, food or diet were used as Chinese keywords and arsenic, food and China were used as English keywords to search for literatures related to the dietary inorganic arsenic exposure published by China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed Database. Using the data from the China National Nutrition and Health Survey (CNNHS) in 2002 to estimate the dietary inorganic arsenic exposure in Chinese residents. The annual cancer cases attributed to the dietary inorganic arsenic exposure were calculated based on the data from Chinese Cancer Registry Annual Report in 2013. The disability adjusted life year (DALY) was calculated using tools built by WHO.@*Results@#The total DALY of cancer caused by the dietary inorganic arsenic exposure was 419.4 thousand, and the DALY rate was 31.47 per 100 000. The DALY of lung cancer in males and females was 237.7 thousand and 102.5 thousand. The DALY of bladder cancer in males and females was 13.2 thousand and 3.9 thousand. The DALY of skin cancer in males and females was 29.4 thousand and 32.8 thousand.@*Conclusion@#In 2013, the Chinese population had a lower burden of cancer due to the dietary exposure to inorganic arsenic.

Dietary Exposure to Inorganic Arsenic in the Norwegian Population

Request from the Norwegian Food Safety Authority: The Norwegian Food Safety Authority (NFSA) requested a statement from the Norwegian Scientific Committee for Food Safety (VKM) on the dietary exposure to inorganic arsenic in the Norwegian population. VKM was asked to comment on the following; 1.) Why the European Food Safety Authority (EFSA) assessment from 2009 found that the Norwegian population had higher dietary exposure to total arsenic than other European populations, 2.) Whether the Norwegian population or special groups of the population have food consumption patterns which could lead to a different dietary exposure to inorganic arsenic than what is reported for the European population, and 3.) Whether the consumption rice and rice products, such as rice cakes, and in Hijiki seaweed could pose additional health risks for children and adults. How VKM has addressed the request: VKM has appointed a working group consisting of members of the Panel on Contaminants and from the VKM secretariat to answer the request. The Panel on Contaminants has reviewed and revised the draft prepared by the working group and finally approved the assessment on dietary exposure to inorganic arsenic in the Norwegian population. What arsenic is and its toxicity to humans: Arsenic is a metalloid occurring in many different chemical forms in the environment. In the terrestrial environment, arsenic is mainly found as inorganic arsenic, i.e. arsenite and arsenate. In the aquatic environment, more than a 100 arsenic species have been identified. The organic form arsenobetaine is the major form in fish and other seafood. Humans are mainly exposed to arsenic through food and drinking water. Food is the major source for most people, but for people living in regions with naturally elevated concentrations of arsenic in groundwater, drinking water is the major source. The toxicity of arsenic species depends on the chemical form, with inorganic arsenic (arsenite and arsenate) being more toxic than organic arsenic compounds. Inorganic arsenic is carcinogenic, but not genotoxic, and is classified as a human carcinogen. Dietary total arsenic exposure in Europe and Norway: The dietary exposure to total arsenic for the Norwegian population was estimated by EFSA (2009). The Norwegian exposure levels were the highest among the European populations. A high exposure to total arsenic for Norwegian adults was also estimated in the Norwegian Fish and Game study (Birgisdottir et al., 2013). Fish and seafood is the main contributor to the dietary exposure to total arsenic, and a high consumption of fish and seafood leads to a high dietary exposure to total arsenic. Dietary inorganic arsenic exposure in Europe and Norway: There was little variation in the estimated dietary exposures to inorganic arsenic for the European populations (EFSA, 2014). The dietary exposure to inorganic arsenic has earlier been estimated for the Norwegian adult population based on a study including participants with high consumption of fish and other seafood and game meat, and participants representing the general population (Birgisdottir et al., 2013). The estimates for inorganic arsenic exposure were within the ranges reported by EFSA (2014), suggesting that Norwegian adults do not have specific eating patterns leading to a different dietary exposure to inorganic arsenic than other European adult populations. In the European populations, the main contributors to dietary exposure of inorganic arsenic were the food groups “grain-based processed products (non rice-based)”, “rice”, “milk and dairy products” and “drinking water” (EFSA, 2014). There is no information regarding specific dietary patterns of Norwegian sub-populations possibly leading to a higher exposure to inorganic arsenic. Fish and other seafood generally contain high levels of total arsenic, but the level of inorganic arsenic is very low. Exposure to inorganic arsenic through consumption of rice and rice products, and Hijiki seaweed The dietary exposures to inorganic arsenic in the European populations are within the range of the BMDL01 values and therefore possible health risks cannot be excluded (EFSA, 2009; EFSA, 2014). The estimated dietary exposure to inorganic arsenic in the Norwegian adult population (Birgisdottir et al., 2013) is also within the range of the BMDL01 values. Rice was identified as one of the main contributors to the dietary exposure to inorganic arsenic in Europe (EFSA, 2014). Rice and rice products contain higher levels of inorganic arsenic than other food groups and individuals with a high consumption of rice and rice products may have a higher exposure to inorganic arsenic than the rest of the population, resulting in an added health risk. For infants and toddlers, rice and rice products are not an important source of inorganic arsenic (EFSA, 2014). According to EFSA (2014) the main contributor to exposure to inorganic arsenic in infants and toddlers was “milk and dairy products”, then “drinking water”, “grain-based processed products (non rice-based)” and “Foods for infants and young children”. However, the dietary exposure to inorganic arsenic in toddlers and children is higher than in adults because of their higher food consumption relative to body weight (EFSA, 2014). Rice cakes are a product, which may contain particularly high levels of inorganic arsenic, and consumption of rice cakes by children will increase their exposure to inorganic arsenic (Livsmeddelsverket 2015, DTU Food 2013). Thus, Norwegian infants and toddlers with a high consumption of rice and rice products, such as rice cakes, may have a higher exposure to inorganic arsenic than other infants and toddlers, resulting in an added health risk. The edible seaweed Hijiki generally contains high levels of inorganic arsenic, whereas other seaweeds contain low levels of inorganic arsenic. Any consumption of Hikiji seaweed will lead to an additional exposure of inorganic arsenic, resulting in an added health risk.

Establishment of arsenic speciation analysis method and application in rice / 中华预防医学杂志

Objective@#A new ion exchange column technology was used to establish an efficient and sensitive method for the detection of inorganic arsenic.@*Methods@#Based on the new As Specia Fast Column, the pretreatment methods, liquid phase separation and mass spectrometry determination conditions of inorganic arsenic in rice were optimized. Finally, arsenic compounds were separated by As Specia Fast Column and detected by liquid chromatography inductively coupled plasma mass spectrometry. The external standard method was used for quantitative analysis. The detection limit, precision and accuracy of the method were determined by measuring the content of arsenic compounds in rice samples and rice standard samples. At the same time, three Guangdong rice samples were selected as the experimental samples of this study, and 1 g of each sample was weighed and measured in parallel three times. The method was compared with the method of liquid chromatography-atomic fluorescence spectrometry (LC-AFS) and liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS) in the national standard.@*Results@#The inorganic arsenic in rice was extracted with 0.5% nitric acid solution at 65 ℃ for 15 h, and the pH was adjusted to alkaline. The mobile phase A (8 mmol/L HNO3, 50 mmol/L NH3·H2O) and mobile phase B (40 mmol/L HNO3, 80 mmol/L NH3·H2O) were used as the mobile phase gradient elution (93%) . Five arsenic compounds can reach baseline separation under the conditions of RF power of 1 500 W and atomization gas flow of 0.97 L/min. The detection limits ranged from 0.114 to 0.331 μg/L, and the inorganic arsenic content in rice samples ranged from 0.063 to 0.232 mg/kg. The results of determination of arsenic compounds in rice flour reference materials were all within the uncertainty range indicated by the standard. The recoveries were 86.7%~106.7%, and the precision was 1.9%-12.5%. Compared with national standards, the results of determination of arsenate in rice were relatively close (using this method, LC-AFS, LC-ICP-MS to detect the content of arsenate in rice samples 1 was 0.231, 0.226, 0.236 mg/kg, respectively). However, due to insufficient sensitivity, the national standard method is difficult to detect low levels of arsenic compounds (Arsenobetaine was not detected in rice sample 1). The method can detect the content of arsenobetaine in rice sample 1 was 0.023 mg/kg.@*Conclusion@#The established method can meet the requirements of inorganic arsenic determination in rice, and it is more rapid and accurate than the current national standard. It can better monitor and evaluate the content of i-As in rice, and provide accurate data for comprehensively grasping and evaluating the safety of rice consumption of residents.

Increased PIT1 and PIT2 Expression in Streptozotocin (STZ)-induced Diabetic Mice Contributes to Uptake of iAs(V) / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study aimed to investigate the susceptibility of mice with streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent inorganic arsenic (iAsV) and the possible molecular mechanism.</p><p><b>METHODS</b>TIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na2HAsO4·12H2O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues.</p><p><b>RESULTS</b>The concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na2HAsO4·12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAsV, were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment.</p><p><b>CONCLUSION</b>The increased uptake of iAsV in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.</p>

Consumo de arsénico y riesgo cardiovascular / Arsenic consumption and cardiovascular risk

El arsénico (As) es un elemento considerado como ubicuo, cuyas fuentes pueden ser naturales o productos de la actividad humana. La exposición a este elemento ocurre principalmente por la vía oral. Las presentaciones inorgánicas del As son consideradas como las más tóxicas. La absorción del As ocurre en el intestino delgado y por medio de acuaporinas ingresa a los hepatocitos, en casos de ingesta crónica el As tiende acumularse en hígado, riñones, corazón, sistema nervioso, pulmones, músculo, tracto gastrointestinal y bazo. El consumo crónico de agua con concentraciones de As por encima del valor de referencia dado por la Organización Mundial de la Salud (OMS) ha demostrado un aumento del riesgo de accidentes vasculares cerebrales (AVC), hipertensión arterial (HTA), aterosclerosis carotidea, enfermedades arteriales periféricas, mortalidad por infarto agudo del miocardio (IAM), aumento en enfermedades cardiovasculares en la población pediátrica y diabetes mellitus tipo II.

Arsenic (As) is an element considered as ubiquitous. Its sources may be natural or manmade. The exposure to this element occurs mainly orally. Inorganic ‘As’ presentations are considered the most toxic. Arsenic absorption occurs in the small intestine, and through aquaporin, entering hepatocytes in chronic intake tends. The element (As) tends to get accumulated in the liver, kidneys, heart, nervous system, lung, muscle, gastrointestinal tract, and spleen. Chronic consumption of water with arsenic concentrations above the reference value given by the World Health Organization has shown an increased risk of cerebrovascular accident (CVA), Hypertension (HT), carotid atherosclerosis, peripheral arterial disease, mortality from acute myocardial infarction (AMI), increased cardiovascular disease in the pediatric population, and type II diabetes mellitus.

Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy.

Assessment of Arsenic Exposure by Measurement of Urinary Speciated Inorganic Arsenic Metabolites in Workers in a Semiconductor Manufacturing Plant

OBJECTIVES: The purpose of this study was to evaluate the exposure to arsenic in preventive maintenance (PM) engineers in a semiconductor industry by detecting speciated inorganic arsenic metabolites in the urine. METHODS: The exposed group included 8 PM engineers from the clean process area and 13 PM engineers from the ion implantation process area; the non-exposed group consisted of 14 office workers from another company who were not occupationally exposed to arsenic. A spot urine specimen was collected from each participant for the detection and measurement of speciated inorganic arsenic metabolites. Metabolites were separated by high performance liquid chromatography-inductively coupled plasma spectrometry-mass spectrometry. RESULTS: Urinary arsenic metabolite concentrations were 1.73 g/L, 0.76 g/L, 3.45 g/L, 43.65 g/L, and 51.32 g/L for trivalent arsenic (As3+), pentavalent arsenic (As5+), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total inorganic arsenic metabolites (As3+ + As5+ + MMA + DMA), respectively, in clean process PM engineers. In ion implantation process PM engineers, the concentrations were 1.74 g/L, 0.39 g/L, 3.08 g/L, 23.17 g/L, 28.92 g/L for As3+, As5+, MMA, DMA, and total inorganic arsenic metabolites, respectively. Levels of urinary As3+, As5+, MMA, and total inorganic arsenic metabolites in clean process PM engineers were significantly higher than that in the non-exposed group. Urinary As3+ and As5+ levels in ion implantation process PM engineers were significantly higher than that in non-exposed group. CONCLUSION: Levels of urinary arsenic metabolites in PM engineers from the clean process and ion implantation process areas were higher than that in office workers. For a complete assessment of arsenic exposure in the semiconductor industry, further studies are needed.

Application of Realgar in Chinese Patent Medicine and Arsenic Dissolution / 环境与健康杂志

Objective To investigate the present status of Chinese patent medicine with realgar (As2S2) and to research arsenic dissolution in different pH values. Methods Data on the amount of Chinese patent medicine with realgar, the content of realgar, the method of taking medicine and so on were collected from the Chinese traditional medicine protection and criterions issued by the Chinese Ministry of Health in 2005, and evaluated the using status of Chinese patent medicine with realgar. The realgar powder was dissolved in solutions at different pH values (1, 3, 5, 7, 9, 11) in 37℃ water for 4 h, respectively, then arsenic was determined with cold trap hydride generation atomic absorption spectrometry to calculate the amount of dissolved arsenic. Results One hundred and twenty-one (3.13%) realgar medicaments were recorded in a total of 3 860 various Chinese patent medicaments, including 74 medicaments with both realgar and cinnabar (HgS) . Of all medicaments with realgar, 97 medicaments (80.17%) were for oral application, 10 medicaments (8.26%) were for external application, and 14 medicaments (11.57%) were for both oral and external application. 45 medicaments with realgar (1.17%) could be used in children; 108 medicaments with realgar (89.26%) contained arsenic 15%; The relative amount of arsenic in medicaments with realgar was from 0.46% to 27.52%. Daily intake of arsenic was 500 mg for 11 medicaments (9.09%). Only inorganic arsenic (iAs) was detected when 1 mg realgar was dissolved in solution with pH values of 1, 3, 5, 7, 9, 11. The levels of dissolved iAs seemed increased with the pH values, which were 1.58 ?g, 1.24 ?g, 1.57 ?g, 1.62 ?g, 2.28 ?g and 4.76 ?g, respectively. Conclusion Considering the common use of realgar in Chinese patent medicine and the high level of arsenic in realgar, the potential danger can not be ignored. It is possible that arsenic in realgar may be much easier to be absorbed in intestine than in stomach.