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The Region Lagunera, a region in northeast Mexico, is undergoing significant problems with the quality of its groundwater, which exceeds the permissible limits of contaminants and/or heavy metals stipulated in Mexican legislation. The present study evaluated chronic toxicity in male goats exposed to arsenic via one ex situ Group 1 (n = 5) and one in situ female goats Group 3 (n = 10). The treatment in Group 1 was carried out in the La Laguna experimental field of the Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP), located in Matamoros, Coahuila, Mexico. Sodium arsenite (2 mg/kg) was orally administered for 84 days to five male Creole goats, aged between four and five years old and weighing between 60 and 70 kg, in order to determine its effect on urine toxicity, libido, and physiological condition, an untreated group (n = 5) was included (Group 2). The experiment in group 3 was conducted on ten female Creole goats, aged between four and six years old and weighing between 40 and 49 kg, in both the contaminated sampling area in the rural community of El Venado and the control sampling area in the rural community of Nuevo Reynosa (Group 4 (n = 5)), in which the arsenic levels were measured in the urine of the exposed goats, as was their physiological condition. Significant differences (p < 0.01) between the groups were found in both the arsenic concentration in the urine and the physiological condition observed in both experimental groups.
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A correction to this paper has been published and can be accessed via link at the top of the paper.
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Exposure to inorganic arsenic (iAs) remains a global public health problem. Urinary arsenicals are the current gold-standard for estimating both iAs exposure and iAs metabolism. However, the distribution of these arsenicals may differ between the urine and target organs. Instead, plasma arsenicals may better represent internal dose and capture target organ exposure to arsenicals. Drinking water iAs, plasma and urinary arsenicals were quantified in individuals living in the Zimapan and Lagunera regions of Mexico. The relationship between drinking water iAs and plasma arsenicals was examined using both Spearman correlations and multivariable linear regression models. In addition, the distribution of arsenicals in plasma and urine was examined and the association between plasma and urinary arsenicals was assessed using both Spearman correlations and multivariable linear regression models. Levels of iAs in drinking water were significantly associated with plasma arsenicals in unadjusted and adjusted analyses and the strength of these associations was similar to that of drinking water iAs and urinary arsenicals. These results suggest that plasma arsenicals are reliable biomarkers of iAs exposure via drinking water. However, there were notable differences between the profiles of arsenicals in the plasma and the urine. Key differences between the proportions of arsenicals in plasma and urine may indicate that urine and plasma arsenicals reflect different aspects of iAs toxicokinetics, including metabolism and excretion.
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Arsenicais/sangue , Exposição Ambiental/análise , Intoxicação por Arsênico , Biomarcadores/metabolismo , Água Potável/análise , Feminino , Humanos , Modelos Lineares , Masculino , México , ToxicocinéticaRESUMO
BACKGROUND: Exposure to inorganic arsenic (iAs) via drinking water is a serious global health threat. Various factors influence susceptibility to iAs-associated health outcomes, including differences in iAs metabolism. Previous studies have shown that obesity is associated with iAs metabolism. It has been hypothesized that this association can be explained by confounding from nutritional factors involved in one-carbon metabolism, such as folate or other B vitamins, whose intake may differ across BMI categories and is known be associated with iAs metabolism. However, no studies have explored whether this association is confounded by nutritional factors. METHODS: We investigated the relationship between body mass index (BMI) and the distribution of urinary arsenic species in a cross-sectional cohort of 1166 adults living in Chihuahua, Mexico from 2008 to 2013. Nutrient intake related to one-carbon metabolism, including folate, vitamin B2, and vitamin B12, was assessed using a food frequency questionnaire developed for Mexican populations. Multivariable linear regression was used to estimate the association between BMI and the distribution of urinary arsenic metabolites. Effect modification by drinking water iAs level and sex was also examined. RESULTS: After adjusting for potential confounders, including age, educational attainment, smoking, alcohol consumption, seafood consumption, water iAs, and sex, BMI was negatively associated with the proportion of urinary inorganic arsenic (%U-iAs) and urinary monomethylated arsenic (%U-MMAs) and positively associated with urinary dimethylated arsenic (%U-DMAs). This relationship was not influenced by additional adjustment for folate, vitamin B2, or vitamin B12 intake. Additionally, there was significant effect modification by both drinking water iAs level and sex. CONCLUSIONS: This study provides further evidence for an association between BMI and arsenic metabolism. However, contrary to previous hypotheses, these results suggest that this association is not confounded by the intake of micronutrients involved in one-carbon metabolism.
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Arsênio/urina , Índice de Massa Corporal , Carbono/metabolismo , Nutrientes/metabolismo , Adulto , Arsênio/análise , Estudos de Coortes , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Masculino , México , Estado Nutricional , FumarRESUMO
OBJECTIVES: Lead exposure is associated with children's growth, but this relationship may depend on the presence of susceptibility factors, including genetic variation. Blood lead levels (BLL) differ by ALAD (aminolevulinic acid dehydratase) genotype. We investigated the association between BLL and growth in Mexican first-graders with different ALAD genotypes. METHODS: Children between the ages of 6-8 years (nâ¯=â¯602) attending first grade in schools within the vicinity of a metal foundry in Torreón, Mexico were enrolled into a randomized controlled trial (RCT) testing the efficacy of iron and/or zinc supplementation on blood lead levels (BLL) and cognition. BLL and anthropometry were assessed at baseline (height, height-for-age z-score (HAZ), knee height, head circumference), after 6 (head circumference) and 12 months (height, HAZ, knee height). Children with ALAD1-1 and ALAD1-2/2-2 were compared. The study sample included 538 and 470 participants who had complete data at baseline and follow-up, respectively. Separate multivariable linear regression models adjusted for covariates were used to test the association between BLL at baseline and each anthropometric measure. Covariates included age, sex, hemoglobin, crowding, and maternal education. BLL x ALAD genotype interaction term was tested. RESULTS: Median BLL (10.1⯵g/dL) did not differ by ALAD genotype. After covariate adjustment, baseline BLL was inversely associated with baseline height, HAZ, and knee height. The association (ß [95% CI]) between BLL and baseline height (-0.38[-0.68, -0.09]), HAZ (-0.07[-0.12, -0.02]) and knee height (-0.14[-0.25, -0.02]), was somewhat stronger in children with ALAD1-2/2-2 than ALAD1-1 (-0.09[-0.16, -0.02], -0.02[-0.03, -0.004] and -0.04[-0.06, -0.01], respectively). No associations between BLL and growth at 6 or 12 months were detected irrespective of ALAD genotype. CONCLUSIONS: BLL was adversely associated with anthropometric measures among Mexican children. ALAD genotype may be a susceptibility factor for the effects of lead on child growth.
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Antropometria , Exposição Ambiental/estatística & dados numéricos , Chumbo , Sintase do Porfobilinogênio/genética , Criança , Genótipo , Humanos , MéxicoRESUMO
Arsenic (As) is a toxic metalloid. Inorganic arsenic (iAs) is a form of As commonly found in drinking water and in some foods. Overwhelming evidence suggests that people chronically exposed to iAs are at risk of developing cancer or cardiovascular, neurological, and metabolic diseases. Although the mechanisms underlying iAs-associated illness remain poorly characterized, a growing body of literature raises the possibility that microRNAs (miRNAs), post-transcriptional gene suppressors, may serve as mediators and/or early indicators of the pathologies associated with iAs exposure. To characterize the circulating miRNA profiles of individuals chronically exposed to iAs, samples of plasma were collected from 109 healthy residents of the city of Zimapán and the Lagunera area in Mexico, the regions with historically high exposures to iAs in drinking water. These plasma samples were analyzed for small RNAs using high-throughput sequencing and for iAs and its methylated metabolites. Associations between plasma levels of arsenic species and miRNAs were evaluated. Six circulating miRNAs (miRs-423-5p, -142-5p -2, -423-5p +1, -320c-1, -320c-2, and -454-5p), two of which have been previously linked to cardiovascular disease and diabetes (miRs-423-5p, -454-5p), were found to be significantly correlated with plasma MAs. No miRNAs were associated with plasma iAs or DMAs after correction for multiple testing. These miRNAs may represent mechanistic links between iAs exposure and disease or serve as markers of disease risks associated with this exposure.
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Arsênio , MicroRNA Circulante , Água Potável , MicroRNAs , Humanos , MéxicoRESUMO
The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women's metabolism of As as indicated by greater proportions of MMAs and smaller proportions of DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 µmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.
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Arsênio/urina , Biomarcadores/sangue , Biomarcadores/urina , Exposição Ambiental/análise , Ácido Fólico/sangue , Homocisteína/sangue , Adulto , Estudos de Coortes , Estudos Transversais , Água Potável/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino , Metilação , México , Gravidez , Gestantes , Análise de Regressão , Vitamina B 12/sangue , Adulto JovemRESUMO
Mitochondrial dysfunction is a hallmark of diabetes, but the metabolic alterations during early stages of the disease remain unknown. The ability of liver cells to rearrange their metabolism plays an important role in compensating the energy shortage and may provide cell survival. Moringa oleifera leaves have been studied for its health properties against diabetes, insulin resistance, and non-alcoholic liver disease. We postulated that M. oleifera executes a protective function on mitochondrial functionality in HepG2 treated with high glucose. We evaluated the effect of high glucose treatment on the mitochondrial function of HepG2 cells using a Seahorse extracellular flux analyzer (Agilent, Santa Clara, CA, USA), blue native polyacrylamide gel electrophoresis (BN-PAGE), and western blot analysis. For assessment of mitochondrial abnormalities, we measured the activity of mitochondrial Complex I and IV as well as uncoupling protein 2, and sirtuin 3 protein contents. Our results demonstrate that, under conditions mimicking the hyperglycemia, Complex I activity, UCP2, Complex III and IV subunits content, supercomplex formation, and acetylation levels are modified with respect to the control condition. However, basal oxygen consumption rate was not affected and mitochondrial reactive oxygen species production remained unchanged in all groups. Treatment of HepG2 cells with M. oleifera extract significantly increased both protein content and mitochondrial complexes activities. Nonetheless, control cells’ respiratory control ratio (RCR) was 4.37 compared to high glucose treated cells’ RCR of 15.3, and glucose plus M. oleifera treated cells’ RCR of 5.2, this indicates high-quality mitochondria and efficient oxidative phosphorylation coupling. Additionally, the state app was not altered between different treatments, suggesting no alteration in respiratory fluxes. These findings enhance understanding of the actions of M. oleifera and suggest that the known antidiabetic property of this plant, at least in part, is mediated through modulating the mitochondrial respiratory chain.
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Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13-43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = -0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = -0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.
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Chumbo/sangue , Sintase do Porfobilinogênio/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Intoxicação por Chumbo/sangue , Modelos Lineares , México , Sintase do Porfobilinogênio/metabolismo , Gravidez , Espectrofotometria Atômica , Adulto JovemRESUMO
OBJECTIVE: To examine the role of iron and zinc in arsenic excretion and metabolism in children. STUDY DESIGN: An analysis of urinary arsenic (UAs) concentrations from a double-blind randomized trial originally testing the efficacy of iron and zinc for lowering blood lead levels in children. A 2 × 2 factorial design was used, with children randomized individually, stratified by sex and classroom, to receive 30?mg ferrous fumarate (n?=?148), 30?mg zinc oxide (n?=?144), iron and zinc together (n?=?148), or placebo (n?=?151). Of the 602 children enrolled, 527 completed the 6-month treatment, and 485 had both baseline and final UAs values. The baseline total UAs concentration ranged from 3.2 to 215.9?µg/L. RESULTS: At baseline, children in the highest tertile of serum ferritin concentration had higher excretion of dimethylarsinic acid (DMA; 1.93?±?0.86%; P?