Research progress on the regulatory mechanism of non-coding RNA in arsenic toxicity / 中华劳动卫生职业病杂志

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.

Intoxicación por arsénico / Arsenic poisoning

Resumen El agua que es consumida por los seres humanos diariamente, también conlleva la ingesta de algunos compuestos químicos, como lo es el arsénico, metaloide que al ser consumido crónicamente es perjudicial para la salud, mismo al que algunos trabajadores podrían estar expuestos en su lugar de trabajo. En las pericias médico forenses los metales toman relevancia cuando producen intoxicaciones, teniendo que discernir si dichas intoxicaciones están en relación con la actividad laboral que desempeña el evaluado o si por el contrario, se deben a la exposición ambiental por consumo en agua o alimentos contaminados en sus hogares. El arsénico es un compuesto muy tóxico, que al no tener sabor ni olor se puede consumir en el agua inadvertidamente, causando un hidroarsenicismo agudo o crónico. Se ha comprobado que el mismo tiene impactos a nivel del sistemas dermatológico, cardiovascular, inmunológico, neurológico, hepático, renal y respiratorio, con influencia en el desarrollo embrionario y con propiedades carcinogénicas importantes. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos doce años, con el objetivo de estudiar las características del Arsénico, su metabolismo y su impacto en la salud de los seres humanos. Se concluye que en Costa Rica es necesario un estudio de poblaciones de riesgo de exposición a arsénico, debido a que es un país con múltiples actividades económicas básicas antropogénicas y por presentar una alta cantidad de volcanes distribuidos en su territorio. Por su parte el médico forense al realizar peritajes en casos de intoxicación debe de analizar ampliamente la relación de causalidad antes de asegurar o descartar la relación laboral.

Abstract The water that is consumed by human beings on a daily basis, also entails the intake of some chemical compounds, such as arsenic, a metalloid that when consumed chronically is harmful to health, the same to which some workers could be exposed in their workplace. In forensic medical expertise, metals become relevant when they produce intoxications, having to discern if such intoxications are related to the work activity performed by the person being evaluated or if, on the contrary, they are due to environmental exposure by consumption of contaminated water or food in their homes. Arsenic is a very toxic compound that, since it has no taste or odor, can be consumed inadvertently in water, causing acute or chronic hydroarsenicism. It has been proven that it has impacts on the dermatological, cardiovascular, immunological, neurological, hepatic, renal and respiratory systems, with influence on embryonic development and with important carcinogenic properties. A bibliographic review was made in different databases, of the articles published on the subject in the last twelve years, with the objective of studying the characteristics of arsenic, its metabolism and its impact on the health of human beings. It is concluded that a study of populations at risk of exposure to arsenic is necessary in Costa Rica, due to the fact that it is a country with multiple basic anthropogenic economic activities and because it has a high number of volcanoes distributed in its territory. The forensic doctor, on the other hand, when performing expert opinions in cases of intoxication, should analyze the causal relationship before assuring or discarding the work relationship.

Hidroarsenicismo: mecanismos de acción asociados a la toxicidad del arsénico / Hydroarsenicism: Mechanisms of action related to arsenic toxicity

La exposición crónica al arsénico (As) inorgánico a través del agua de bebida da lugar al desarrollo de la enfermedad conocida como hidroarsenicismo. Esta enfermedad presenta sintomatología característica, sin embargo, para la mayoría de los efectos tóxicos que produce del As aún no se conoce en detalle el mecanismo de acción tóxica. Los mecanismos moleculares de acción del arsenito (unión a grupos sulfhidrilos) y del arseniato (sustitución del fosfato) están bien identificados, sin embargo, las consecuencias a nivel subcelular, celular, tisular y orgánico de esos mecanismos todavía presentan muchos huecos por llenar. A nivel subcelular y celular, la generación de especies reactivas de oxígeno (ERO) y de nitrógeno (ERN) son los mecanismos de acción tóxica del As más estudiados últimamente. Se los ha vinculado con la diferenciación y proliferación de queratinocitos, con la disfunción endotelial, con la resistencia a la insulina, con la inducción de peroxidación lipídica en hígado, de necrosis tubular renal y con cambios en la expresión del receptor estrogénico. Por último, la respuesta celular a proteínas no plegadas (como consecuencia del estrés del retículo endoplásmico) podría ser un mecanismo para explicar la afectación de la inmunidad humoral y la celular.

Chronic exposure to inorganic arsenic (As) through drinking water leads to the development of the disease known as hydroarsenicism. This disease presents characteristic symptomatology but the mechanisms underlying most of the toxic effects produced by As are not fully understand. The molecular mechanisms of action of arsenite (binding to sulfhydryl groups) and arsenate (phosphate substitution) are well identified, however, the consequences at the subcellular, cellular, tissue and organic levels of these mechanisms still have many gaps to fill. At the subcellular and cellular level, the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the most studied mechanisms of toxic action. They have been linked to the differentiation and proliferation of keratinocytes, endothelial dysfunction, insulin resistance, induction of lipid peroxidation in the liver, renal tubular necrosis and changes in the expression of estrogen receptor. Finally, the cellular response to unfolded proteins (as a consequence of the stress of the endoplasmic reticulum) could be a mechanism to explain the affectation of humoral and cellular immunity.

Arsenicosis presenting with cutaneous squamous cell carcinoma: A case report

@#A 29-year-old male with eleven-year history of hyperkeratotic papules and speckled pigmentation developed cutaneous squamous cell carcinoma. Arsenicosis was confirmed by elevated hair arsenic level, and histopathologic findings of arsenical keratosis and one lesion showing carcinoma-in-situ. Chronic arsenic exposure has been found to activate inflammatory and carcinogenic pathways leading to development of pre-malignant and malignant lesions. A multi-disciplinary approach involving healthcare specialists and environmentalists is crucial in source control and management of long-term complications.

Vascular injury in spontaneous subacute toxicosis caused by organic arsenic in cattle / Injúria vascular na toxicose subaguda espontânea causada por arsênio orgânico em bovinos

Monosodium methanearsonate (MSMA) is an organic form of arsenic present in the formulations of some herbicides. Accidental ingestion of pasture contaminated with arsenic may lead to toxicosis in cattle. Almost 200 head of cattle maintained in an area sprayed with MSMA presented with intense diarrhea and dehydration after grazing. Subsequently, 16 of these animals died. Toxic levels of arsenic (>1.5µg/g) were detected in the kidney, liver, urine, and skeletal muscle of 6 animals. At gross inspection were observed multifocal to coalescent ulcers in the mucosa from on the forestomachs associated with hemorrhagic areas and marked wall edema. Microscopic examination mainly showed fibrinoid necrosis of vessels with multifocal thrombosis associated with ischemic infarction that were characterized by large transmural necrotic areas in the forestomachs. The clinical and pathological changes interestingly showed that this form of arsenic although considered less toxic, has caused severe vascular injury in forestomachs of cattle.(AU)

Metano-arseniato ácido monossódico (MSMA) é uma forma orgânica de arsênio, presente nas formulações de alguns herbicidas. A ingestão acidental de pasto contaminado por arsênio pode levar a toxicose em bovinos. Aproximadamente 200 bovinos que estavam em uma pastagem pulverizada com MSMA manifestaram intensa diarreia e desidratação após o pastejo. Subsequentemente, 16 animais morreram. Níveis tóxicos de arsênio (>1.5µg/g) foram detectados no rim, fígado, urina e músculo esquelético de 6 animais. A inspeção macroscópica revelou úlceras multifocais a coalescentes na mucosa de pré-estômagos, adjacentes a focos de hemorragia e intenso edema de parede. A avaliação microscópica revelou, predominantemente, necrose fibrinoide de vasos com trombose multifocal associada a infarto, caracterizado por grandes áreas de necrose transmural em pré-estômagos. As alterações clínicas e patológicas, interessantemente, demonstraram que esta forma de arsênio, apesar de ser considerada menos tóxica, causou severa injúria vascular em pré-estômagos de bovinos.(AU)

Speckled pigmentation and palmoplantar keratoses leading to the mass detection of chronic arsenic poisoning

@#<p style="text-align: justify;">Arsenic is a known human carcinogen and skin manifestations are the earliest and most specific markers of chronic arsenic poisoning. A 43-year-old man from Luzon presented at the Section of Dermatology with a one-year history of hyperkeratotic papules and plaques on the palms and soles. Numerous round hypopigmented macules were scattered on the upper back. Initial 24-hour urine arsenic level was elevated at 288mcg/liter. The patient underwent successful chelation with N-acetylpenicillamine and the palmoplantar keratoses were treated with cryotherapy and topical 20% salicylic acid in white petrolatum. In cooperation with the Department of Health, a comprehensive health and environmental assessment was conducted in the affected communities. This case highlights the role of dermatologists in the diagnosis and management of this public health problem.</p>

Food Habits Among The Arsenic Exposed Population In The Rural Areas Of Nepal And Bangladesh

@#Arsenicosis, the illness due to chronic arsenic toxicity is prevalent in both Nepal and Bangladesh. The occurrence of arsenicosis depends upon many factors including food and nutrition. The objective of this study was to find out any difference of food habits among the arsenic exposed households of both countries and the relationship with the occurrence of arsenicosis. This was a cross-sectional comparative study, conducted among the arsenic exposed rural households of Nawalparasi district in Nepal and Faridpur district in Bangladesh. A total of 190 and 200 female rural households from Nepal and Bangladesh were selected respectively as the respondents. The majority of the respondents of both countries were under the age of 40 years. The prevalence of arsenicosis was found significantly low (χ2 = 8.847; p=.002) among the Nepalese households (7.3%) than that of Bangladeshi households (11.0%). As a staple food, rice, vegetables and pulses were more common among the Nepalese households in comparison to that of Bangladesh (χ2=5.739; p=.017). In addition to staple food Nepalese households were found to take significantly more (p<.05) bread (74.7%), egg (73.2%), milk (68.9%) and fruits (58.4%). In contrast, Bangladeshi households took a little more meat (59.0%) and fish (73.5%). To get arsenic-safe water, 39.5% Bangladeshi households used a filter while a few Nepalese households (2.6%) used that. Nepalese households were found to take more protein and vitamins rich foods as staple food compared to that of Bangladeshi households, which might play a role in the low occurrence of arsenicosis amongst them.

Speckled pigmentation and palmoplantar keratoses leading to the mass detection of chronic arsenic poisoning

Arsenic is a known human carcinogen and skin manifestations are the earliest and most specific markers of chronic arsenic poisoning. A 43-year-old man from Luzon presented at the Section of Dermatology with a one-year history of hyperkeratotic papules and plaques on the palms and soles. Numerous round hypopigmented macules were scattered on the upper back. Initial 24-hour urine arsenic level was elevated at 288mcg/liter. The patient underwent successful chelation with N-acetylpenicillamine and the palmoplantar keratoses were treated with cryotherapy and topical 20% salicylic acid in white petrolatum. In cooperation with the Department of Health, a comprehensive health and environmental assessment was conducted in the affected communities. This case highlights the role of dermatologists in the diagnosis and management of this public health problem.

A Clinical Study of Multiple Non-melanoma Skin Cancers over 4 Years in a Single Institution Center / 대한피부과학회지

BACKGROUND: Non-melanoma skin cancers (NMSCs, basal cell carcinoma [BCC], and squamous cell carcinoma, [SCC]) are skin conditions, and the propensity of NMSCs to develop multiple tumors may be associated with some genodermatoses, arsenic poisoning, and chronic exposure to radiation or coal tar. OBJECTIVE: To report our experience of treating multiple NMSCs and to investigate the clinical characteristics of NMSCs. METHODS: We retrospectively evaluated 16 patients who had been diagnosed with NMSCs from May 2010 to December 2014. RESULTS: The male-female sex ratio was 0.6:1 in the patients with multiple BCCs and SCCs. The most frequent age group was the seventh decade (75%). The mean patient age was 76.36 years. The most common involved site was the face, particularly the cheek (54.3%). Nodular BCCs were the most frequent (61.9%), followed by infiltrate BCCs (28.6%) and superficial BCCs (9.5%). Among the SCCs, the moderately differentiated SCCs were the most frequent (50%). More NMSCs were found on the left than on the right side of the head and neck areas in both sexes. Development of BCC (68.8%) was more frequent than that of SCC in sun-exposed areas. CONCLUSION: In our study, differences in the demographic variables, such as age, sex, or residence were found between the patients with multiple BCCs and SCCs. The incidence of BCC has markedly increased, which is mainly because of the increment of aged people in their residence, along with environmental factors. Further cohort studies that include cumulative lifetime sun exposure and a large sample size are needed.

Riesgo para la población rural en zonas con alto contenido de arsénico en agua / Risk for rural population in areas with high arsenic water content

El arsénico (As) es un tóxico natural presente en aguas subterráneas y superficiales. En este trabajo se estimó el riesgo por ingesta de agua subterránea con elevadas concentraciones de As para pobladores rurales bonaerenses. Además se consideró una fuente adicional de exposición a la presencia de As en tejidos blandos del pejerrey (Odontesthes bonariensis), que es la especie nativa de mayor importancia comercial. La concentración de As se determinó por espectroscopía de emisión atómica por plasma de acoplamiento inductivo (ICP-OES). En las muestras de agua subterránea las concentraciones se hallaron en el rango de < 10-170 µg/l, mientras que en músculos de peces estuvo comprendida entre 0,29-8,41 µg/g y en hígado entre 0,24-8,98 µg/g (en peso seco). El hidroarsenicismo crónico regional endémico Argentino (HACREA), enfermedad que se origina por el consumo de cantidades variables de As en un largo período de tiempo, genera diferentes afecciones de piel. El riesgo estimado por ingesta de agua subterránea en todas las localidades estudiadas superó el valor aceptado de riesgo individual máximo (10-5), según la Agencia de Protección Ambiental de los Estados Unidos (USEPA). Los niveles de As hallados en tejidos de peces, sugieren que existiría transferencia de este elemento desde el agua a los distintos órganos, que podría resultar perjudicial para el consumo humano.

Arsenic (As) is a natural toxic present in groundwater and surface water. This study estimated the risk of ingestion of high As concentrations present in groundwater for a rural population in Buenos Aires Province. The presence of As in soft tissues of silverside (Odontesthes bonariensis) was also considered as an additional source of As exposure, which is the native species of major commercial importance. Arsenic concentration was determined by inductively coupled plasma atomic emission spectroscopy (ICP-OES). In water samples As concentrations were found in the range of < 10-170 µg/l, in fish muscle the concentration range was between 0,29 to 8,41 µg/g, and in liver between 0,24 to 8,98 µg/g, of dry weight. The endemic regional chronic hydroarsenicism Argentino (ERCHA), a disease caused by consumption of varying As concentrations during a long time, generates different skin pathologies. The risk estimated for groundwater intake in this rural population at all sites studied exceeded the accepted value of maximum individual risk (10-5), according to United States Environmental Protection Agency (USEPA). As concentration in fish tissues, could be shown transference of this element to different organs, being harmful for human consumption.

Relationship between changes of genetic damage and development of disease in patients with arsenism caused by coal-burning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of genetic damage in patients with arsenism caused by coal-burning in 9 years. To analyze the relationship between the changes of genetic damage and disease progression and provide a basis for condition monitoring.</p><p><b>METHODS</b>Of 206 arsenism patients from the area with endemic arsenism in Guizhou province were tracking surveyed in February 1998 and divided into 4 groups, including suspicious, mild, moderate and severe poisoning group. Another 67 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were surveyed. Over a 9-year follow-up, 131 arsenism patients and 45 controls with the complete biochemical indexes among them were selected as subjects in December 2006. Arsenic (As) concentration of urine and hair were detected by silver diethyldithiocarbamate spectrophotometry (Ag-DDC). Micronucleis (MN) and chromosome aberrations (CA) were analyzed by conventional methods. DNA single-strand breaks of peripheral blood were measured by single cell gel electrophoresis (SCGE), and the tail lengths of comet were used to measure DNA damage.</p><p><b>RESULTS</b>Among the control, suspicious, mild, moderate and severe arsenic poisoning group, the As contents of urine and hair were respectively (34.16 ± 10.25), (52.35 ± 22.41), (62.26 ± 31.13), (71.43 ± 49.92), (78.45 ± 50.64) µg/L and (1.37 ± 0.56), (3.69 ± 1.78), (4.88 ± 3.49), (5.21 ± 3.10), (6.25 ± 4.04) µg/g in 2006, which were lower than that 9 years before (urine as contents were (36.07 ± 20.70), (73.65 ± 41.33) , (90.92 ± 82.14) , (126.55 ± 107.31) and (139.44 ± 90.90) µg/L, and hair As contents were (1.41 ± 1.18), (4.85 ± 4.20), (5.72 ± 4.07) , (6.43 ± 4.32) and (7.19 ± 4.68) µg/g, respectively, F value was 10.63, 7.72, 14.66, 11.00 respectively, all P values were < 0.05). Except for suspicious poisoning group, the differences of urine As contents in the other groups all showed significance (P < 0.05). The incidences of MN were (0.238 ± 0.130) %, (0.268 ± 0.192) %, (0.283 ± 0.157) % and (0.391 ± 0.233)%; the incidences of CA were (14.36 ± 5.44) %, (18.09 ± 6.49) %, (19.38 ± 5.63)% and (19.83 ± 5.84) %; the tail lengths of comet were (29.88 ± 13.81) , (29.84 ± 12.80) , (34.50 ± 9.88) and (41.58 ± 12.98) µm respectively in 2006 for all poisoning groups; which were higher than that 9 years before(the incidences of MN were (0.163 ± 0.051) %, (0.186 ± 0.117) %, (0.196 ± 0.104) % and (0.273 ± 0.142) %; the incidences of CA were (13.18 ± 5.17)%, (14.48 ± 6.61)%, (15.67 ± 8.49) % and (16.90 ± 8.38) %; the tail lengths of comet were (15.07 ± 12.93) , (19.57 ± 8.80) , (27.03 ± 10.77) and (34.71 ± 14.95) µm) , except for the incidences of MN and CA in suspicious poisoning group and of MN in mild poisoning group , the differences of the three indexes in the other groups were significant (P < 0.05) . The state of illness of arsenic poisoning patients aggravated 9 years later. With the increase of urine and hair As contents and the development of arsenism, the incidences of MN, CA and the tail lengths of comet of all poisoning groups increased. There were positive correlations among them (r values were respectively 0.212, 0.316, 0.232, 0.263, 0.321, 0.654 and 0.760) (P < 0.05).</p><p><b>CONCLUSION</b>The exacerbation of genetic damage was related to constantly high arsenic loads. The accumulation of genetic damage and its irreversibility might be one of the important reasons of the development of arsenism and cancer.</p>

Effects of arsenic poisoning on neuronal cell apoptosis and mRNA and protein expression of calpain 1, calpain 2, and cdk5/p25 / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of arsenic on neuronal cell apoptosis and the mRNA and protein expression of calpain 1, calpain 2, and cyclin-dependent kinases 5 (cdk5)/p25 and to provide a scientific basis for the research on neurotoxic mechanism of arsenic trioxide (As2O3).</p><p><b>METHODS</b>Primary cultured rat neurons were divided into untreated control group, dimethyl sulfoxide (DMSO) solvent control group, and 1, 5, and 10 µmol/L As2O3 treated groups. Eight hours after being treated with As2O3, cell apoptosis rate was determined by flow cytometry, the mRNA expression of calpain 1, calpain 2, cdk5, and p35 was measured by real-time fluorescence quantitative PCR, and the protein expression of calpain 1, calpain 2, cdk5, p35, and p25 was measured by Western blot.</p><p><b>RESULTS</b>Compared with those in the untreated control group and DMSO solvent control group, the cell apoptosis rates in the 5 and 10 µmol/L As2O3 treated groups were significantly increased (P < 0.05). The mRNA expression levels of calpain 1 were 6.36±3.26, 7.11±5.13, and 7.47±2.59 in the 1, 5, and 10 µmol/L As2O3 treated groups, respectively, and the mRNA expression levels of cdk5 were 1.27±0.19, 1.54±0.04, and 1.79±0.21 in the 1, 5, and 10 µmol/L As2O3 treated groups, respectively, which were significantly higher than those in the untreated group (0.72±0.15 and 1.77±0.87) and those in the DMSO solvent control group (0.96±1.23 and 1.18±0.09) (P < 0.05). The mRNA expression levels of p35 in the 1 and 5 µmol/L As2O3 treated groups were 2.17±0.59 and 2.51±0.51, respectively, which were significantly higher than that in the untreated control group (1.26±0.37) (P < 0.05). The protein expression levels of calpain 1 were 0.37±0.10, 0.42±0.13, and 0.51±0.18 in the 1, 5, and 10 µmol/L As2O3 treated groups, respectively, which were significantly higher than those in the untreated control group (0.11±0.08) and DMSO solvent control group (0.13±0.07) (P < 0.05). In the 5 and 10 µmol/L As2O3 treated groups, the protein expression levels of cdk5 were 0.34±0.12 and 0.37±0.21, while the protein expression levels of p25 were 0.31±0.23 and 0.55±0.16, all of which were significantly higher than those in the untreated control group and DMSO solvent control group (P < 0.05). The protein expression levels of p35 were reduced in the 5 µmol/L As2O3 treated group (0.31±0.23) and 10 µmol/L As2O3 treated group (0.26±0.16), as compared with those in the untreated control group and DMSO solvent control group (P < 0.05). The mRNA and protein expression of calpain 2 showed no significant differences between all groups (P > 0.05).</p><p><b>CONCLUSION</b>The calpain 1-cdk5/p25 pathway may be involved in the process of As2O3-induced neuronal cell apoptosis.</p>

Arsenic pesticides and environmental pollution: exposure, poisoning, hazards and recommendations

Arsenic is a metalloid element. Acute high-dose exposure to arsenic can cause severe systemic toxicity and death. Lower dose chronic arsenic exposure can result in subacute toxicity that can include peripheral sensorimotor neuropathy, skin eruptions, and hepatotoxicity. Long-term effects of arsenic exposure include an in Due to the physiologic effects of the arsenic on all body systems, thus, chronic arsenic-poisoned patient is a major nursing challenge. The critical care nurse provides valuable assessment and interventions that prevent major multisystem complications from arsenic toxicity

Effectiveness of zinc in modulating perinatal effects of arsenic on the teratological effects in mice offspring

Exposure to arsenic via drinking water is considered as a worldwide problem. Studies have shown that arsenic exposure during pregnancy affects embryogenesis and offspring development in rats and mice. Zinc as a micronutrient regulates many physiological functions, including an antioxidative role under various toxic conditions. However, studies on the perinatal protective effect of zinc on offspring need further attention. The present study was designed to evaluate the potential protective role of zinc in mitigating the adverse effects in the offspring of arsenic exposure during pregnancy. The arsenic (40mg/kg body weight) and zinc (4% w/v) doses formed the only drinking fluid source for the experimental groups of dams during the perinatal period of the experiment. The early development of sensory motor coordination reflexes together with morphological development in the male pups was measured during the weaning period. In adolescence, the offspring were tested for their motor behavior. The enzyme γ-glutamyl transferase (γ-GT) and the oxidative stress indices like reduced glutathione (GSH) and lipid peroxidation (TBARS) were also estimated in the serum of the young adult male mice. Perinatal arsenic exposure caused depletion in body weight gain, delay in morphological development and retardation in the development of all sensory motor reflexes of the pups. In young adults, significant decrease in motor behavior with significant decrease in GSH level in the serum was observed. On the other hand, γ-GT and TBARS were significantly increased in the serum due to arsenic treatment. However, animals exposed to arsenic in the presence of zinc showed a remarkable ameliorating effect of zinc on all observed teratological and biochemical arsenic toxicity in male offspring. It was observed that zinc has an antioxidative role in the perinatal toxicity of arsenic. It is concluded from the present study that zinc consumed during the perinatal period of pregnancy can ameliorate the possible toxicities of arsenic exposure in the offspring by acting as an ameliorative supplement.

Identificación y cuantificación del arsénico unido a las proteínas de tejidos cardiovasculares de pacientes sometidos a cirugía de revascularización coronaria / Identification and quantification of protein-linked arsenic in cardiovascular tissues from patients submitted to coronary revascularization

Introducción: Los efectos de la intoxicación con Arsénico (As) como enfermedades cardiovasculares (CV), pigmentaciones y oclusiones arteriales coronarias están asociados con la ingestión de As inorgánico a través del agua de bebida y a exposiciones ambientales. La unión del As (III) a proteínas y la metilación del As podría ser una primera etapa en el mecanismo de detoxificación. Objetivo: Evaluar la unión de As a proteínas en aurícula derecha y vena safena (VS) en sujetos expuestos de la Región de Antofagasta. Métodos: Se estudió la asociación As-proteína en el citosol de AD y VS de 6 pacientes con enfermedad coronaria grave de la Región de Antofagasta. Para el fraccionamiento del citosol se utilizaron columnas de exclusión molecular de tres diferentes rangos de masas. El perfil del As se detectó por Espectrometría de Masas Inductivamente Acoplado (ICP-MS) y por Espectrosco-pía Ultra Violeta - Visible de las fracciones moleculares (enlaces As- tiolatos de proteínas). Resultados: En todos los casos el As estuvo ampliamente distribuido en todo el intervalo de fracciones para AUD y VS. Los porcentajes de As colectado en las fracciones de las diferentes columnas usadas fueron 10, 25 y 50 por ciento. En la especiación de As en el citosol, por Cromatografía Líquida de Alta Resolución acoplada a la Espectrometría de Masas (IC-HPLC-ICP-MS), solamente se encontró As(III) y As(V) con una distribución Gaussiana para ambas especies, siendo la relación As(III)/As(V) constante para AUD y VS. Conclusión: En los tejidos CV existe asociación As - proteína lo cual podría implicar que el As está unido a biocompuestos de diferente peso molecular a través de grupos sulfhidrilos vecinales. Es probable que el As en AUD y VS se una a fracciones proteicas de masa molecular superior a 80 kDA y a subunidades de la estructura cuaternaria de la proteína nativa.

Background: The effects of arsenic (As) toxi-city - cardiovascular disease, pigmentation, coronary artery occlusion- come from ingestion of contaminated drinking water and environmental exposure. Protein linkage or As(III) and As methylation may be a first step in detoxification. The aim of this study is to evaluate protein linkage of As in the right atrium (RA) and saphenous vein (SV) of As exposed subjects from Antofagasta, Chile Method: As-protein linkage was studied in the cytosol of AD and SV obtained from 6 patients operated on for coronary artery disease. Molecular exclusion columns of 3 different mass ranges were used to obtain the cytosol fraction. As species were detected by induction coupled mass spectrometry and visible ultraviolet spectrometry (links of As and protein thyolates). Results: As was widely distributed in AD and SV in all subjects. As collected in the 3 different columns used were 10 per cent, 25 per cent and 50 per cent. Only As(III) and As(V) were obtained through the method used (IC-HPLC-ICP-MS); a normal distribution was evident for both As species. The relation As(III)/As(V) was similar in AD and SV. Conclusion: A linkage of As and proteins through neighbor sulphidryl groups is present in cardiovascular tissues of exposed subjects. It is likely that As is linked to >80 kDA protein fractions and to quaternary subu-nits or the native protein.

The regulation mechanism of protein kinase Cδ on arsenic liver injury caused by coal-burning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of mRNA transcriptional and protein expressions of protein kinase Cδ (PKCδ) on the development of arsenic liver injury caused by coal-burning.</p><p><b>METHODS</b>Population study:133 arsenic exposures were selected as arsenic exposure groups including the ward non-patient group (25 cases) , no obvious hepatopathy group (38 cases) , mild (43 cases) and moderate to severe hepatopathy group (27 cases) from the area with endemic arsenism in Guizhou province. Another 34 healthy residents were selected as the control group in non-arsenic pollution village. The urine and peripheral blood were collected from the subjects. The arsenic contents in urine and mRNA expressions of PKCδ in peripheral blood were detected. Animal experiment study:thirty wistar rats were randomly by random number table divided into control group, drinking water arsenic poisoning group and coal-burning arsenic poisoning group (i.e., low, medium and high arsenic contaminated grain group) by random number table method, including 6 rats in each group. The control group was fed normally for 3 months, drinking water arsenic poisoning group and coal-burning arsenic poisoning groups were fed respectively with 10 mg/kg As2O3 solution and different concentrations (25, 50 and 100 mg/kg) of arsenic-containing feed which was persisted 3 months. The arsenic contents in urine, mRNA expression levels of PKCδ in peripheral blood and liver tissue and the protein expression levels of phosphorylated protein kinase Cδ(pPKCδ) in liver tissue were detected.</p><p><b>RESULTS</b>The median(quartile) of arsenic contents in urine were 25.58 (18.62-40.73), 56.66 (38.93-76.77), 64.90 (39.55- 98.37) and 75.47 (41.30-109.70) µg/g Cr respectively for the non-patient group, no obvious hepatopathy group, mild and moderate to severe hepatopathy group. The levels were higher than that in the control group (23.34 (17.84-37.45) µg/g Cr) (P < 0.05), except for the ward non-patient group. The arsenic contents in rat urine were 2223.61 (472.98-3976.73), 701.16 (194.01-1300.27), 1060.94 (246.33-2585.47) and 3101.11 (1919.97-5407.07) µg/g Cr, respectively for the drinking water arsenic poisoning group, the low, medium and high dosage arsenic grain contamination groups, all higher than that in the control group (94.32 (22.65-195.25) µg/g Cr) (P < 0.05) . The protein expressions of pPKCδ in liver tissue were 324.83 ± 25.06, 278.50 ± 30.57, 308.83 ± 34.67 and 326.33 ± 35.09, which were significantly higher than that in the control group (240.17 ± 28.07) (P < 0.05) . The protein expression levels of pPKCδ in liver cell membrane were 0.49 ± 0.06,0.33 ± 0.05,0.37 ± 0.06 and 0.50 ± 0.08, which were significantly higher than that in the control group (0.28 ± 0.04) (P < 0.05) . The protein expression levels of pPKCδ in liver cell cytoplasm were 0.38 ± 0.06,0.31 ± 0.05, 0.35 ± 0.05 and 0.36 ± 0.05, which were significantly higher than that in the control group (0.24 ± 0.05) (P < 0.05).</p><p><b>CONCLUSION</b>The arsenic may regulate protein expressions of pPKCδ and induce its membrane translocation, and cause the development of arsenic liver injury caused by coal-burning.</p>

Regulating effects of Rosa roxburghii tratt preparation on immune function in arseniasis patients caused by coal burning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the influence of rosa roxburghii tratt preparation on immune function of arseniasis patients caused by burning coal.</p><p><b>METHODS</b>According to the diagnosis standard for endemic arseniasis(WS/T 211-2001), 62 cases of arseniasis patients who resided in endemic arseniasis area in Guizhou province were selected and divided stratified randomly into two groups: rosa roxburghii tratt juice treatment group and superoxide dismutase(SOD)-enriched rosa roxburghii tratt juice treatment group, with 31 patients in each group.Each patient took 120 ml/d rosa roxburghii tratt preparation or SOD-enriched rosa roxburghii tratt orally for one month. Another 30 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were selected as controls. A 2 ml blood and 50 ml urine samples were collected from individuals and the urine arsenic contents, peripheral blood T-lymphocyte subsets (CD3(+), CD4(+), CD8(+) T cell), serum immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) were detected. The differences between more than two groups on above indicators were compared. The correlations between urinary arsenic and immune parameters were analyzed.</p><p><b>RESULTS</b>Among the rosa roxburghii tratt juice group, SOD-enriched rosa roxburghii tratt juice before intervention group and the control group, the levels of urine arsenic were (76.55 ± 23.02) , (72.60 ± 25.91) and (26.33 ± 11.30) µg/g Cr respectively and IgG were (11.31 ± 1.68), (11.35 ± 1.94) and (9.23 ± 1.75) g/L respectively. The differences were statistically significant(F values were 82.01, 13.82, both P values < 0.05). After intervention with rosa roxburghii tratt preparation, the levels of urine arsenic were (53.21 ± 16.51) and (51.72 ± 17.70)µg/g Cr, both decreased than before intervention (t values were 5.80 and 3.78, both P values < 0.05). The levels of CD3(+) were (44.47 ± 7.14)%, (43.44 ± 6.61)% and (70.78 ± 5.26)%, CD4(+) were (29.87 ± 5.67)%, (29.42 ± 5.87)% and (46.08 ± 5.87)%, CD4(+)/CD8(+) were(1.25 ± 0.42), (1.22 ± 0.39) and (1.79 ± 0.26) and C4 were (0.13 ± 0.08), (0.13 ± 0.09) and (0.20 ± 0.11) g/L respectively among the two treatment group before intervention and the control group. The differences were significant (F values were 178.04, 76.71, 23.13 and 5.26, all P values < 0.05). After intervention, the levels of CD3(+) were (59.73 ± 7.38)% and (66.31 ± 7.57)%, CD4(+) were (34.00 ± 7.97)% and (39.11 ± 5.81)%, CD4(+)/CD8(+) were (1.41 ± 0.37) and(1.58 ± 0.26), all increased than before intervention(t values were 12.47, 25.18, 5.41, 10.47, 3.22 and 5.05, all P values < 0.05). The levels of urine arsenic and CD3(+), CD4(+), CD4(+)/CD8(+), C4 were inversely correlated correlation, while positive correlation existed between the level of urine arsenic and IgG(r values were -0.68, -0.56, -0.51, -0.43 and 0.36, all P values < 0.01).</p><p><b>CONCLUSIONS</b>The level of urinary arsenic level is closely related to immune function suppression in arseniasis patients caused by burning coal, rosa roxburghii tratt preparation can effectively improve immune function of arseniasis patients.</p>

The mRNA expression of mitogen-activated protein kinase signal pathway related genes in the blood of arseniasis patients caused by burning coal / 中华预防医学杂志

<p><b>OBJECTIVE</b>To detect the mRNA expression of ERK1, ERK2, JNK1 and P38 gene in mitogen-activated protein kinase(MAPK) path way in the arseniasis patients caused by burning coal.</p><p><b>METHODS</b>70 arseniasis patients caused by burning coal at Jiaole village XingRen county in December 2006 were selected as case group, and another 30 villagers with similar living habits, matched gender and age, healthy physical condition without history of burning high arsenic coal were selected as control group from 12 km nearby the same village.Silver diethyl dithiocarbamate method (Ag-DDC) was taken to detect the arsenic contents in the environmental media, food, and arsenic level in the urine and hair of arseniasis patients.On the principle of informed consent, the peripheral blood was collected from the patients. The total RNA was extracted with Trizol method and cDNA was reversed from it. The mRNA expression of ERK1, ERK2, JNK1 and P38 gene in MAPK path way were tested by real-time fluorescent quantitative PCR (QT-PCR).</p><p><b>RESULTS</b>A total of 70 cases of arseniasis patients (31 cases of mild, 25 cases of moderate and 14 cases of severe) and 30 cases of control were chosen. The median (quartile) of arsenic contents in the indoor air, outdoor air, coal, chili and corn were 0.079 (0.053-0.117) mg/m(3) ,0.007 (0.002-0.015) mg/m(3) , 93.010 (39.460-211.740) mg/kg, 3.460(0.550-16.760) mg/kg and 1.500(0.300-4.140) mg/kg respectively. They were above the national health standards. The median (quartile) of arsenic contents in the soil, rice and drinking water were separately 12.130(4.230-24.820) mg/kg, 0.650(0.300-0.980) mg/kg and 0.043(0.012-0.089)mg/kg, which were within the national health standards. Compared with the control group ((26.97 ± 9.71)µg/g Cr), arsenic level in the patients' urine ((71.48 ± 22.74)µg/g Cr) increased significantly, the differences were significant (F = 90.38, P < 0.01). Compared with the control group ((1.58 ± 1.07)µg/g), arsenic level in the patients' hair ((4.45 ± 2.78) µg/g) increased significantly, the differences were significant (F = 48.22, P < 0.01). The relative expression amount of the median(quartile) for ERK2, JNK1 mRNA were 0.0667 (0.0378-0.1371) and 0.0013 (0.0009-0.0025), respectively. Compared with the control group 0.1744 (0.1009-0.1985) and 0.0022 (0.0017-0.0030) , only the decreases of ERK2, JNK1 mRNA expression was significant (χ(2) = 15.10, 14.25, P < 0.01), and no significance in the other index. ERK2 mRNA relative expression for mild, medium and severe groups were separately 0.0818 (0.0408-0.1509) ,0.0582 (0.0154-0.1699) and 0.0588 (0.0399-0.1034) . Compared with the control group (0.1744 (0.1099-0.1985) ), there was significant difference (Z = -2.89, -3.19, -2.67, P < 0.01). JNK1 mRNA relative expression were 0.0012 (0.0007-0.001 57), 0.0019 (0.0011-0.0035), 0.0013 (0.0010-0.0026), respectively. Compared with the control group (0.0022 (0.0017-0.0030) ), significances were found in the mild groups (Z = -3.72, P < 0.01).</p><p><b>CONCLUSIONS</b>Arsenic could induce the changes of ERK2 and JNK1mRNA expression in the MAPK path way in arseniasis patients.It suggests that the MAPK signaling pathway take part in the occurrence and development process of arseniasis caused by burning coal.</p>

The establishment of the arsenic poisoning rats model caused by corn flour baked by high-arsenic coal / 中华预防医学杂志

<p><b>OBJECTIVE</b>To establish coal arsenic poisoning rat model by feeding the rats with the corn powder baked by high arsenic coal as the main raw material.</p><p><b>METHODS</b>Fifty Wistar rats, healthy, were randomly divided into 5 groups according to the figures of their weights, including control group, drinking arsenic poisoning water group, low, medium and high arsenic contaminated grain group, 10 rats for each.Rats in control group and drinking arsenic poisoning water group were fed with standard feed without any arsenic containing. Rats in water group would drink 100 mg/L As2O3 solution and the rats in arsenic grain groups would be fed with the arsenic contaminated grain at the dose of 25, 50 and 100 mg/kg, respectively. The duration would last for 3 months.General situation and weight were observed. At the same time, the arsenic contents of urine, hair, liver and kidney of the rats in each group were detected, as well as the histopathology changes of liver and kidney, and the ultra structure of liver was observed.</p><p><b>RESULTS</b>The arsenic contents of urine (median(min-max)) of the rats in the arsenic water group, low, medium and high arsenic grain groups were separately 3055.59 (722.43-6389.05), 635.96(367.85-1551.31), 1453.84 (593.27-5302.94) and 3101.11 (666.64-6858.61) µg/g Cr; while the arsenic contents of hair of the rats in the above groups were separately (23.07 ± 10.38), (8.87 ± 3.31), (12.43 ± 6.65) and (25.68 ± 7.16) µg/g; the arsenic contents of liver of the rats in the above groups were separately (5.68 ± 3.13), (2.64 ± 1.52), (3.89 ± 1.76) and (5.34 ± 2.78) µg/g; and the arsenic contents of kidney were separately (6.90 ± 1.94), (3.48 ± 1.96), (5.03 ± 2.08) and (7.02 ± 1.62) µg/g; which were all significantly higher than those in the control group (86.70 (49.71-106.104) µg/g Cr,(1.28 ± 0.37) µg/g, (1.01 ± 0.34) µg/g and (1.82 ± 1.09) µg/g, respectively). The difference showed significance (P < 0.05). Under electron microscope detection, we observed the reduction of mitochondrial, the blurred mitochondrial cristae, some disappeared ridges, the reduced rough endoplasmic reticulum, and irregular uneven nuclear in the liver cells of rats in arsenic contaminated grain group. The contents of aspartate transaminase (AST) and total bile acid (TBA) in medium and high arsenic contaminated grain group were respectively (196.17 ± 46.18), (212.40 ± 35.14) U/L and (11.74 ± 4.07), (19.19 ± 4.68)µmol/L, which were higher than it in the control group (separately (143.10 ± 29.13) U/L and (6.23 ± 2.95)µmol/L). The contents of glutathione-S-transferases(GST), γ-glutamyltranspeptidase (GGT)and blood urea nitrogen (BUN)in high arsenic contaminated grain group were separately (196.21 ± 47.38)U/L, (1.71 ± 0.66)U/L, (9.54 ± 1.95)mmol/L, which were higher than that in the control group ((134.93 ± 24.80 )U/L, (0.75 ± 0.36)U/L, (7.67 ± 1.02)mmol/L, respectively). The contents of cholinesterase (CHE) in low, medium and high arsenic contaminated grain group were separately (259.90 ± 52.71)U/L, (263.44 ± 66.06)U/L and (244.90 ± 36.14)U/L, the contents of total protein(TP) in rats of high arsenic contaminated grain group were (62.64 ± 5.50)g/L, which was all lower than that in the control group ((448.33 ± 59.67)U/L, (69.38 ± 4.24)g/L, respectively). The contents of TBA in high arsenic contaminated grain group ( (19.19 ± 4.68) µmol/L) was higher than that in drinking water arsenic poisoning group ((15.15 ± 2.64)µmol/L). The differences of the above indexes were all significant (P < 0.05).</p><p><b>CONCLUSION</b>The results showed the arsenic poisoning rat model produced by coal-burning were successfully established.</p>

Intoxicação aguda por metano arsonato ácido monossódico em bovinos / Acute poisoning by monosodium methanearsonic acid in cattle

O presente trabalho estudou a intoxicação acidental por arsênico em um lote de 24 vacas Girolando, as quais tiveram acesso a pasto pulverizado com herbicida à base de metano arsonato ácido monossódico (MSMA). Os bovinos apresentaram apatia, anorexia e diarreia profusa. Foram necropsiados na fazenda dois animais de 14 que morreram. Os principais achados macroscópicos foram úlceras abomasais e congestão renal. No exame microscópico, as principais lesões observadas foram abomasite e omasite necro-hemorrágica multifocal acentuada e, nos rins, necrose tubular difusa. As concentrações médias de arsênico em vacas com sinais clínicos foram 1,19±0,40, 10,52±2,16 e 76,06±48,37ppm no sangue, leite e fezes, respectivamente. Os níveis de arsênico encontrados em dois animais necropsiados foram 25,58 e 23,85ppm em fígado, e 28,71 e 35,94ppm em rins, respectivamente. No feto de uma vaca necropsiada, os níveis de arsênico mensurados no fígado e rim foram 9,0 e 8,92ppm, respectivamente. A concentração de arsênico no capim do piquete pulverizado foi 111,58ppm. No Brasil, o uso MSMA na composição de pesticidas e herbicidas é permitido somente para uso agrícola, mas não pecuário. A utilização desse ou de outros produtos à base de arsênico na pecuária pode causar altos índices de mortalidade no rebanho, além de diminuição da produção e contaminação de produtos de origem animal.

Poisoning by monosodium methanearsonic acid (MSMA) is reported in a herd of 24 Girolando cows that were introduced into a pasture sprayed with the herbicide. Clinical signs were apathy, anorexia, and profuse diarrhea. Fourteen cows died and two were necropsied. Abomasal ulcers and renal congestion was observed. Main histologic lesions were multifocal, accentuated, necrotizing and hemorrhagic abomasitis and omasitis, and tubular necrosis in the kidneys. Mean arsenic concentrations in cows with clinical signs were 1.19±0.40, 10.52±2.16, and 76.06±48.37ppm in blood, milk, and feces, respectively. In the two necropsied cows arsenic concentrations were 25.58 and 23.85ppm in liver, and 28.71 and 35.94ppm in kidney, respectively. In a fetus of a cow that was necropsied, arsenic concentrations were 9.0 and 8.92ppm in liver and kidney, respectively. Arsenic concentration in the grass collected from the paddock sprayed with MSMA was 111.58ppm. In Brazil, the use of MSMA in the composition of herbicides is allowed only for agricultural use, not for livestock. The use of arsenic based products for livestock can lead to high mortality rates in the herd, as well as reduced production and contamination of animal products.