Arsenic exposure and non-carcinogenic health effects.

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders.

Effect of selenomethionine supplementation in food on the excretion and toxicity of arsenic exposure in female mice.

Selenium (Se) is an essential component of several major metabolic pathways and controls immune function. Arsenic (As) is a human carcinogen with immunotoxic and genotoxic activities, functioning mainly by producing oxidative stress. Due to the ability of Se to interact with As and to possibly block its toxic effects, we investigated the impact of dietary Se-methionine (Se-Met) supplementation on the toxicity of As exposure in vivo in a mouse model. Sufficient and excess levels of Se-Met (0.2 and 2 ppm, respectively) were fed to C57BL/6N female mice exposed to sodium arsenite (3, 6 and 10 mg/kg) in tap water for 9 days. We observed that As exposure increased Se-Met excretion in the urine. Se-Met supplementation increased the relative liver weight and decreased the concentration of total liver proteins in animals exposed to 10 mg/kg of As. Se-Met supplementation maintained a normal pool of glutathione in the liver and increased glutathione peroxidase concentration, although the lipoperoxidation level was increased by Se-Met even without As exposure. Se-Met supplementation helped to maintain the CD4/CD8 ratio of lymphocytes in the spleen, although it increased the proportion of B cells. Se-Met supplementation prior to As exposure increased the secretion of interleukin-4, IL-12 and interferon-γ and the stimulation index of the spleen cells in in vitro assays. Se-Met intake improved the basal immunological parameters but did not reduce the damage caused by oxidative stress after low-dose As exposure.

[Overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico]. / Sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México.

The study was aimed at determining the prevalence of overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico. For this purpose, a cross-cut study was conducted between 2010 and 2011, in which the body mass index (BMI) was calculated. To define overweight and obesity, the categories of the World Health Organization (WHO) and the Mexican Official Standard (NOM, Spanish acronym) were used. 227 nahuas (77,5% women) were included. According to WHO’s guidelines, the rate for overweight among nahuas was 41%, and 36.5% for obesity; according to NOM, it was 11.4 and 69.2% respectively. In conclusion, the prevalence of overweight and obesity among indigenous nahuas is high. Studies should be conducted to determine the prevalence and risk factors in order to develop prevention strategies based on this information to improve the health quality of these populations.

Sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México / Overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico

El estudio tuvo como objetivo determinar la frecuencia de sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México. Para ello, se realizó un estudio transversal entre los años 2010-2011; donde se calculó el índice de masa corporal (IMC). Para la definición de sobrepeso y obesidad se emplearon las categorías de la Organización Mundial de la Salud (OMS) y los de la Norma Oficial Mexicana (NOM). Se incluyó 227 nahuas (77,5% mujeres). Según los lineamientos de la OMS, la proporción de nahuas con sobrepeso fue de 41%, y de obesidad 36,5%; y según la NOM fue de 11,4 y 69,2% respectivamente. En conclusión, la frecuencia de sobrepeso y obesidad en indígenas nahuas es alta. Deben realizarse estudios enfocados a determinar la prevalencia y factores de riesgo y, con ello, desarrollar estrategias de prevención que mejoren la calidad de salud de estas poblaciones.

The study was aimed at determining the prevalence of overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico. For this purpose, a cross-cut study was conducted between 2010 and 2011, in which the body mass index (BMI) was calculated. To define overweight and obesity, the categories of the World Health Organization (WHO) and the Mexican Official Standard (NOM, Spanish acronym) were used. 227 nahuas (77,5% women) were included. According to WHO’s guidelines, the rate for overweight among nahuas was 41%, and 36.5% for obesity; according to NOM, it was 11.4 and 69.2% respectively. In conclusion, the prevalence of overweight and obesity among indigenous nahuas is high. Studies should be conducted to determine the prevalence and risk factors in order to develop prevention strategies based on this information to improve the health quality of these populations.

Dose-dependent urinary phenotype of inorganic arsenic methylation in mice with a focus on trivalent methylated metabolites.

Inorganic arsenic (iAs) exposure has been associated with the increased risk of various forms of cancer and of non-cancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate. The results of metabolic and toxicity studies using mice have been entirely applicable to other species including humans. The goal of this study was to investigate the phenotype for the trivalent and pentavalent arsenic metabolites in relation to arsenite dose via immediate analysis of fresh urine samples, while preventing the oxidation of unstable methylated AsIII-containing metabolites. Female mice (C57BL/6) received sodium arsenite by gavage at doses of 0, 3, 6 or 10 mg As/kg/day for 9 days, after which trivalent methylated arsenicals were detected in 100% of urine samples; these arsenicals were not detected in the urine of control mice. The amount of DMAsIII detected in urine depended on the dose of arsenite administered and was determined to be 50.2%, 31.4% and 16.5% of the total urinary arsenic in mice exposed to 3, 6, or 10 mg/kg/day, respectively. This relationship is consistent with the hypothesis of inhibition or saturation of iAs methylation. Understanding the in vivo production of MAsIII and DMAsIII in mice exposed to iAs could aid in developing a biologically based dose-response model for iAs.

Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress.

Chronic exposure to high fluoride (F(-)) may lead to local tissue disturbances, known as fluorosis. F(-) is an oxidising agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins. The goals of the current study were to evaluate whether F(-) exposure affected the oral glucose tolerance test (OGTT) in C57BL6 mice; and to determine the mechanisms at work in glucose homeostasis at the cellular level, in mouse pancreatic beta-cells (betaTC-6) exposed to F(-). Mice received 45 mgl(-1) F(-), as NaF, via drinking water, and cells were exposed for 12h to NaF (equivalent to 0, 0.007, 0.045, 0.180, 1.35 or 2.26 mM F(-)) at a basal or stimulatory glucose concentration (2.8 or 16.6mM, respectively). Mice showed marginal hyperglycemia an impaired glucose tolerance after 4 weeks of F(-) exposure, while beta-cells exposed to 1.35 and 2.26 mM F(-) had significantly lower insulin mRNA expression and subsequent secretion in the presence of the stimulatory glucose concentration. Western blot analyses did not show any alteration in the levels of glucose transporter-2 protein beta-cells on exposure to F(-)in vitro. However, oxidative stress evaluated by the functional activity of superoxide dismutase (SOD) and generation of the superoxide anion (O(2)(-)), showed significantly decreased SOD activity, in a dose-dependent manner. This was accompanied by an increase in the generation of O(2)(-), and decreased mitochondrial membrane potential in F(-) exposed cells. Insulin secretion was lower in beta-cells exposed to F(-), even in the presence of glibenclamide, the ATP-sensitive K(+) (K(ATP)) channel blocker, suggesting down-regulation of the K(ATP) channel in the cell. Exposure to high levels of F(-) in drinking water may decrease insulin mRNA and its secretion from beta-cells, and might therefore affect the OGTT.

Non-optimal levels of dietary selenomethionine alter splenocyte response and modify oxidative stress markers in female mice.

Many studies evaluating the effects of selenium (Se) status on immunity utilize inorganic Se, although selenomethionine (Se-Met) has been suggested to be more bioavailable and less toxic. In the current study, we investigated the effects of dietary Se-Met on immune system function and cellular redox status in C57BL/6N female mice fed with low (0.02 ppm), sufficient (0.2 ppm, control group), or excess Se-Met (2 ppm) in the diet for 50 days. Low Se-Met intake reduced glutathione peroxidase (GPx) activity and glutathione concentration without modifying lipoperoxidation. While low Se-Met intake also reduced the number of B cells in the spleen, it increased mitogen-induced proliferation, IL-4 and IL-12 secretion when compared to the sufficient Se-Met intake group. In comparison to controls, excess Se-Met intake increased splenocyte proliferation and reduced B cell numbers, IL-4, and IL-12 secretion without affecting oxidative stress markers. These data suggest that Se-Met supplementation should be carefully evaluated as it many influence immune function.

Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic.

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.